Pereskia aculeata Miller leaves present in vivo topical anti-inflammatory activity in models of acute and chronic dermatitis.

PubMed

Pinto, Nícolas de Castro Campos; Machado, Danielle Cunha; da Silva, Josiane Mello; Conegundes, Jéssica Leiras Mota; Gualberto, Ana Cristina Moura; Gameiro, Jacy; Moreira Chedier, Luciana; Castañon, Maria Christina Marques Nogueira; Scio, Elita

2015-09-15

The leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used in Brazilian traditional medicine as emollients and to treat skin wounds and inflammation. This study investigated the topical anti-inflammatory activity of the hexane fraction (HF) obtained from the methanol extract of the leaves of this species in models of acute and chronic ear dermatitis in mice. Mice ear edema was induced by topical application of croton oil, arachidonic acid, capsaicin, ethyl-phenylpropiolate and phenol; and by subcutaneous injection of histamine. Ear biopsies were obtained to determine the levels of IL-1β, IL-6 and TNF-α cytokines by ELISA assay. Histopathological analysis was also performed to evaluate the HF activity in croton oil multiple application test. In addition, acute dermal irritation/corrosion test in rats was accomplished. HF chemical characterization was performed by GC-MS analysis. HF intensively reduced the inflammatory process induced by all irritant agents used, except for arachidonic acid. This activity is related, at least in part, to the reduction of IL-6 and TNF-α cytokines levels. Moreover, when the glucocorticoid receptor antagonist mifepristone was used, HF failed to respond to the croton oil application.The results strongly suggested a glucocorticoid-like effect, which was reinforced by the presence of considerable amounts of sterol compounds identified in HF. The acute dermal irritaton/corrosion test showed no signs of toxicity. This study showed that the acute and chronic anti-inflammatory activity of P. aculeata leaves is very promising, and corroborates to better understand their ethnopharmacological applications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antinociceptive Effect of the Essential Oil Obtained from the Leaves of Croton cordiifolius Baill. (Euphorbiaceae) in Mice

PubMed Central

Nogueira, Lenise de Morais; da Silva, Monalisa Ribeiro; dos Santos, Simone Maria; de Albuquerque, Julianna Ferreira Cavalcanti; Ferraz, Igor Cavalcanti; de Albuquerque, Thaíse Torres; Mota, Carlos Renato França de Carvalho; Araújo, Renata Mendonça; Viana, Glauce Socorro de Barros; Martins, René Duarte; Ximenes, Rafael Matos

2015-01-01

Croton cordiifolius Baill. is a shrub known as “quebra-faca” and is used to treat inflammation, pain, wounds, and gastrointestinal disturbances in the semiarid region in the northeast of Brazil. In an ethnobotanical survey in the state of Pernambuco, “quebra-faca” use was cited in 33% of the interviews. Thus, we decided to evaluate the antinociceptive effects of the essential oil from C. cordiifolius (CcEO). Chemical analysis by gas chromatography-mass spectrometry revealed 1,8-cineole (25.09%) and α-phellandrene (15.43%) as major constituents. Antinociceptive activity was evaluated using murine models of chemically induced pain (writhing induced by acetic acid, formalin, capsaicin, and glutamate tests). Opioid and central nervous systems (CNS) involvement were also investigated. Regarding antinociceptive activity, CcEO (50 and 100 mg/kg) reduced the number of writhing responses induced by acetic acid and decreased the licking times in both phases of the formalin test. CcEO also was evaluated in capsaicin- and glutamate-induced nociception. While no effect was observed in the capsaicin test, CcEO (100 mg/kg) was effective in the glutamate test. Naloxone, an opioid antagonist, did not affect the antinociceptive activity of CcEO in writhing test. In conclusion, the antinociceptive effect of CcEO could be explained, at least in part, by inhibition of the glutamatergic system. PMID:25821494

Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs

PubMed Central

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

Background Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%), and neral (31.5%). The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs) (35–90 mm). IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally) significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg), which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of fungal infections and skin inflammation that should be explored in future studies. PMID:25242268

Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs.

PubMed

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

Background Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods The chemical profile of LGEO as determined by gas chromatography-mass spectrometry analysis revealed two major components: geranial (42.2%), and neral (31.5%). The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results LGEO exhibited promising antifungal effect against Candida albicans, C.tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs) (35-90 mm). IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally) significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg), which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of fungal infections and skin inflammation that should be explored in future studies.

Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs.

PubMed

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. The chemical profile of LGEO as determined by gas chromatography-mass spectrometry analysis revealed two major components: geranial (42.2%), and neral (31.5%). The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs) (35-90 mm). IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally) significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg), which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. RESULTS of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of fungal infections and skin inflammation that should be explored in future studies.

Ethnopharmacological study and topical anti-inflammatory activity of crude extract from Poikilacanthus glandulosus (Nees) Ariza leaves.

PubMed

de Brum, Thiele Faccim; Camponogara, Camila; da Silva Jesus, Roberta; Belke, Bianca Vargas; Piana, Mariana; Boligon, Aline Augusti; Pires, Fernanda Brum; Oliveira, Sara Marchesan; da Rosa, Marcelo Barcellos; de Freitas Bauermann, Liliane

2016-12-04

Ethnopharmacological studies are important tools as records and documentation of the empirical uses of medicinal plants in traditional communities with the purpose of generating useful knowledge to lead to the development of new medicines, biodiversity conservation and enhancement of knowledge and local culture. Poikilacanthus glandulosus is widely used by the population of City of Santiago, in Brazil, nevertheless, it does not have any validation regarding its use and its medicinal effects. The objective of this study was to perform one ethnopharmacological survey about P. glandulosus in the City of Santiago and determine the anti-inflammatory activity in order to prove its uses in popular medicine. Personal and ethnopharmacological data were collected through a prepared questionnaire. The phytochemical analysis was performed observing the individual methodology for each reaction and by HPLC-UV. The antiedematogenic and anti-inflammatory (cell infiltration and histological procedure) activities of the P. glandulosus (0.01-1000μg/ear) were evaluated in the ear edema model induced by topical application of croton oil. P. glandulosus is known in City of Santiago as "Gaiana" and its macerated leaves and branches are prepared with alcohol or sugarcane liquor especially for insect bites, cicatrization and inflammation. HPLC analysis revealed the presence of maslinic acid (2.024±0.10mg/g), uvaol (0.124±0.02mg/g) and sitosterol (0.502±0.05mg/g). The topical application of crude extract of P. glandulosus reduced in a dose-dependent manner the croton oil-induced ear edema and myeloperoxidase activity (neutrophils infiltration marker) with maximum inhibition of 87±2% and 64±12%, respectively at 1000µg/ear. Dexamethasone (100µg/ear), used as a positive control, inhibited croton oil-induced ear edema in 89±3% and decreased myeloperoxidase activity in 50±3%. Both P. glandulosus as dexamethasone reduced cell infiltration when evaluated by histological procedure CONCLUSION: This work allowed us to understand the specie P. glandulosus through ethnopharmacological study and it showed that the crude extract presented antiedematogenic and anti-inflammatory actions, proving their traditional use as anti-inflammatory. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antifungal activity of essential oils of Croton species from the Brazilian Caatinga biome.

PubMed

Fontenelle, R O S; Morais, S M; Brito, E H S; Brilhante, R S N; Cordeiro, R A; Nascimento, N R F; Kerntopf, M R; Sidrim, J J C; Rocha, M F G

2008-05-01

To find new antifungal agents among essential oils from Brazilian Croton species. Plant leaves were steam distilled and the obtained essential oils were analyzed by gas chromatography/mass spectroscopy. The main constituents were estragole and anethole for Croton zehntneri, methyl-eugenol and bicyclogermacrene for Croton nepetaefolius and spathulenol and bicyclogermacrene for Croton argyrophylloides. The antifungal activity of essential oils was evaluated against Candida albicans, Candida tropicalis and Microsporum canis by the agar-well diffusion method and the minimum inhibitory concentration (MIC) by the broth microdilution method. Essential oils of Croton species demonstrated better activity against M. canis. Among the three plants C. argyrophylloides showed the best results, with MIC ranging from 9 to 19 microg ml(-1). The acute administration of the essential oil up to 3 g kg(-1) by the oral route to mice was devoid of overt toxicity. The studied essential oils are active in vitro against the dermatophyte M. canis and present relative lack of acute toxicity in vivo. Because of its antifungal activity and low toxicity, the essential oils of studied Croton species are promising sources for new phytotherapeutic agents to treat dermatophytosis.

Chemomodulatory Potential of Flaxseed Oil Against DMBA/Croton Oil-Induced Skin Carcinogenesis in Mice.

PubMed

Sharma, Jyoti; Singh, Ritu; Goyal, P K

2016-09-01

The present study was conducted to evaluate the potential of flaxseed oil to prevent chemically induced skin cancer in mice. Cancer was induced on 2-stage skin carcinogenesis model by single topical application of 7,12 dimethylbenz [a]anthracene (DMBA), as, initiator, and two weeks later it was promoted by croton oil treatment thrice a week on the dorsal surface of mice for 16 weeks. Flaxseed oil (FSO; 100µL/animal/d) was orally administered 1 week before and 1 week after DMBA application (Peri-initiation stage). The animals of the FSO-administered group showed a significant reduction in tumor incidence (76.67%), cumulative number of tumors (37), tumor yield (3.7), and tumor burden (4.81) when compared with the carcinogen-treated control animals. Biochemical parameters in skin and liver tissue such as LPO and phase I enzymes were significantly (P < .01) reduced in the FSO-treated experimental group, whereas the phase II enzymes (GST, DT-diaphorase) and antioxidant parameters (GSH, GPx, SOD, catalase, and vitamin C) exhibited a significant (P < .01) elevation when compared with the animals of the carcinogen-treated control group. Histopathological alterations in the carcinogen-treated control animals were also observed in the form of epidermal hyperplasia, keratinized pearl formation, and acanthosis in skin and tumors, whereas these were found to be reduced after FSO administration. The results of the present study demonstrate that the oral administration of FSO has the potential to modulate the levels of LPO, antioxidants, and detoxification enzymes in the DMBA-croton oil-induced skin carcinogenesis in mice. © The Author(s) 2015.

Anti-inflammation activity of fruit essential oil from Cinnamomum insularimontanum Hayata.

PubMed

Lin, Chien-Tsong; Chen, Chi-Jung; Lin, Ting-Yu; Tung, Judia Chen; Wang, Sheng-Yang

2008-12-01

In this study, the fruit essential oil of Cinnamomum insularimontanum was prepared by using water distillation. Followed by GC-MS analysis, the composition of fruit essential oil was characterized. The main constituents of essential oil were alpha-pinene (9.45%), camphene (1.70%), beta-pinene (4.30%), limonene (1.76%), citronellal (24.64%), citronellol (16.78%), and citral (35.89%). According to the results obtained from nitric oxide (NO) inhibitory activity assay, crude essential oil and its dominant compound (citral) presented the significant NO production inhibitory activity, IC(50) of crude essential oil and citral were 18.68 and 13.18microg/mL, respectively. Moreover, based on the results obtained from the protein expression assay, the expression of IKK, iNOS, and nuclear NF-kappaB was decreased and IkappaBalpha was increased in dose-dependent manners, it proved that the anti-inflammatory mechanism of citral was blocked via the NF-kappaB pathway, but it could not efficiently suppress the activity on COX-2. In addition, citral exhibited a potent anti-inflammatory activity in the assay of croton oil-induced mice ear edema, when the dosage was 0.1 and 0.3mg per ear, the inflammation would reduce to 22% and 83%, respectively. The results presented that the fruit essential oil of C. insularimontanum and/or citral may have a great potential to develop the anti-inflammatory medicine in the future.

Skipjack tuna (Katsuwonus pelamis) eyeball oil exerts an anti-inflammatory effect by inhibiting NF-κB and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice.

PubMed

Jeong, Da-Hyun; Kim, Koth-Bong-Woo-Ri; Kim, Min-Ji; Kang, Bo-Kyeong; Ahn, Dong-Hyun

2016-11-01

The effect of tuna eyeball oil (TEO) on lipopolysaccharide (LPS)-induced inflammation in macrophage cells was investigated. TEO had no cytotoxicity in cell viability as compared to the control in LPS induced RAW 264.7 cells. TEO reduced the levels of NO and pro-inflammatory cytokines by up to 50% in a dose-dependent manner. The expression of NF-κB and MAPKs as well as iNOS and COX-2 proteins was reduced by TEO, which suggests that its anti-inflammatory activity is related to the suppression of the NF-κB and MAPK signaling pathways. The rate of formation of ear edema was reduced compared to that in the control at the highest dose tested. In an acute toxicity test, no mice were killed by TEO doses of up to 5000mg/kg body weight during the two week observation period. These results suggested that TEO may have a significant effect on inflammatory factors and be a potential anti-inflammatory therapeutic. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees (Acanthaceae).

PubMed

Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile

2011-01-01

This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase.

PubMed

Nelson, C J; How, T; Lysle, D T

1999-11-01

The present study investigated the effects of morphine on the irritant contact sensitivity (ICS) and contact hypersensitivity (CHS) reaction. ICS was induced by croton oil application on the pinnae of naïve rats. Morphine injected prior to croton oil application did not affect the ICS response when assessed by measurements of pinnae thickness. CHS was induced by applying the antigen 2,4-dinitro-1-fluorobenzene (DNFB) to the pinnae of rats sensitized to DNFB. Rats received an injection of morphine prior to either initial antigen exposure (sensitization) or antigen reexposure (challenge). Morphine prior to challenge, but not sensitization, resulted in a pronounced enhancement of the CHS response as measured by pinna thickness. Quantitative PCR also showed increased IFN-gamma mRNA levels in the inflamed tissue of morphine-treated rats. Naltrexone blocked the morphine-induced enhancement of the CHS response. The differential effects of morphine suggest that opioids have a more pronounced effect on in vivo immune responses that involve immunological memory. Copyright 1999 Academic Press.

Rose geranium essential oil as a source of new and safe anti-inflammatory drugs

PubMed Central

Boukhatem, Mohamed Nadjib; Kameli, Abdelkrim; Ferhat, Mohamed Amine; Saidi, Fairouz; Mekarnia, Maamar

2013-01-01

Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile. PMID:24103319

Essential oil of Croton zehntneri and its major constituent anethole display gastroprotective effect by increasing the surface mucous layer.

PubMed

Coelho-de-Souza, Andrelina N; Lahlou, Saad; Barreto, João E F; Yum, Maria E M; Oliveira, Ariclécio C; Oliveira, Hermógenes D; Celedônio, Nathalia R; Feitosa, Roney G F; Duarte, Gloria P; Santos, Cláudia F; de Albuquerque, Aline A C; Leal-Cardoso, José H

2013-06-01

Croton zehntneri, a plant native to northeastern Brazil, is widely used in folk medicine to treat gastrointestinal problems and has rich essential oil content. The effects of the essential oil of Croton zehntneri (EOCZ) and its main constituent anethole on several models of gastric lesions were studied in mice and rats. Oral treatment with EOCZ and anethole, both at doses of 30-300 mg/kg, caused similar and dose-dependent gastroprotection against ethanol- and indomethacin-induced gastric damage, but did not change cold-restraint stress-induced ulcers in rats. Furthermore, EOCZ and anethole (both at 30 and 300 mg/kg) similarly and significantly increased the mucus production by the gastric mucosa, measured by Alcian blue binding, in ethanol-induced ulcer model. However, at the same doses, neither EOCZ nor anethole promoted significant alteration in gastric production of non-protein sulfhydryl groups. In pylorus-ligated model, neither EOCZ nor anethole (both at 30 and 300 mg/kg) had a significant effect on the volume of gastric juice, pH, or total acidity. The results of this study show for the first time that EOCZ possesses a gastroprotective potential, an effect mostly attributed to the action of anethole. This activity is related predominantly to the ability of EOCZ and anethole to enhance the production of gastric wall mucus, an important gastroprotective factor. Furthermore, they suggest that EOCZ has potential therapeutic application for the treatment of gastric ulcers. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.

Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema.

PubMed

Savetsky, Ira L; Torrisi, Jeremy S; Cuzzone, Daniel A; Ghanta, Swapna; Albano, Nicholas J; Gardenier, Jason C; Joseph, Walter J; Mehrara, Babak J

2014-07-15

Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity-induced lymphatic dysfunction modulates the pathological effects of lymphatic injury in a mouse model. We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals were fed a high-fat diet and control animals were fed a normal chow diet for 8-10 wk. We then surgically ablated the superficial and deep lymphatics of the midportion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Compared with lean control mice, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45(+) and CD4(+) cell inflammation (P < 0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. In conclusion, obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury. Copyright © 2014 the American Physiological Society.

Enhancement of the Norfloxacin Antibiotic Activity by Gaseous Contact with the Essential Oil of Croton zehntneri

PubMed Central

Coutinho, HDM; Matias, EFF; Santos, KKA; Tintino, SR; Souza, CES; Guedes, GMM; Santos, FAD; Costa, JGM; Falcão-Silva, VS; Siqueira-Júnior, JP

2010-01-01

This is the first on the modulation of norfloxacin antibiotic activity by the volatile compounds of an essential oil. We report the chemical composition and antibiotic modifying activity of the essential oil extracted from the leaves of Croton zehntneri Pax et Hoffm (variety estragole), using the minimal inhibitory dose method and gaseous contact. The leaves of Croton zehntneri Pax et Hoffm (Euphorbiaceae) were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC/MS), and to inhibitory activity of efflux pump by gaseous contact. The main component of the essential oil of C. zehntneri was estragole (76,8%). The gaseous components of the oil enhanced the inhibition zone of norfloxacin in 39,5%. This result shows that this oil influences the antibiotic activity of norfloxacin, possibly affecting the bacterial NorA efflux system, and may be used as an adjuvant in the antibiotic therapy of multidrug resistant pathogens. PMID:21264094

Mild pyrolysis of P3HB/Switchgrass blends for the production of bio-oil enriched with crotonic acid

USDA-ARS?s Scientific Manuscript database

The mild pyrolysis of switchgrass/poly-3-hydroxybutyrate (P3HB) blends that mimic P3HB-producing switchgrass lines was studied in a pilot scale fluidized bed reactor with the goal of simultaneously producing crotonic acid and switchgrass-based bio-oil. Factors such as pyrolysis temperature, residenc...

An aspirin-triggered lipoxin A4 stable analog displays a unique topical anti-inflammatory profile.

PubMed

Schottelius, Arndt J; Giesen, Claudia; Asadullah, Khusru; Fierro, Iolanda M; Colgan, Sean P; Bauman, John; Guilford, William; Perez, Hector D; Parkinson, John F

2002-12-15

Lipoxins and 15-epi-lipoxins are counter-regulatory lipid mediators that modulate leukocyte trafficking and promote the resolution of inflammation. To assess the potential of lipoxins as novel anti-inflammatory agents, a stable 15-epi-lipoxin A(4) analog, 15-epi-16-p-fluorophenoxy-lipoxin A(4) methyl ester (ATLa), was synthesized by total organic synthesis and examined for efficacy relative to a potent leukotriene B(4) (LTB(4)) receptor antagonist (LTB(4)R-Ant) and the clinically used topical glucocorticoid methylprednisolone aceponate. In vitro, ATLa was 100-fold more potent than LTB(4)R-Ant for inhibiting neutrophil chemotaxis and trans-epithelial cell migration induced by fMLP, but was approximately 10-fold less potent than the LTB(4)R-Ant in blocking responses to LTB(4). A broad panel of cutaneous inflammation models that display pathological aspects of psoriasis, atopic dermatitis, and allergic contact dermatitis was used to directly compare the topical efficacy of ATLa with that of LTB(4)R-Ant and methylprednisolone aceponate. ATLa was efficacious in all models tested: LTB(4)/Iloprost-, calcium ionophore-, croton oil-, and mezerein-induced inflammation and trimellitic anhydride-induced allergic delayed-type hypersensitivity. ATLa was efficacious in mouse and guinea pig skin inflammation models, exhibiting dose-dependent effects on edema, neutrophil or eosinophil infiltration, and epidermal hyperproliferation. We conclude that the LXA(4) and aspirin-triggered LXA(4) pathways play key anti-inflammatory roles in vivo. Moreover, these results suggest that ATLa and related LXA(4) analogs may have broad therapeutic potential in inflammatory disorders and could provide an alternative to corticosteroids in certain clinical settings.

Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

PubMed

Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

2018-04-13

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

Studies on promoting action in skin carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saffiotti, U.; Shubik, P.

1963-01-01

A number of substances were tested for carcinogenic promoting activity in Swiss mice by applying them twice weekly to the clipped dorsal skin, beginning 1 wk after a single application of 9,10-dimethyl-1, 2-benzanthracene (DMBA; 1 to 1.5% in mineral oil). Tests with silver nitrate (10% aqueous), iodoacetic acid (0.9% in acetone, fumaric acid (1% in acetone), ethylphenylpropiolate (5% in acetone), trihydroxymethylanthraquinone. (Emodin; 0.5% in acetone), oleic alcohol, monostearin (5% in acetone) and sorbitan monolaurate were essentially negative; when a single application of croton oil (5% in mineral oil) was interspersed between the carcinogen and silver nitrate, 6/20 mice developed 14more » benign tumors and 1 carcinoma. N-Dodecane showed moderate promoting activity (26 tumors, with 2 carcinomas, in 12/30 mice). Tests of several petroleum fractions showed high initial promoting activity (404 tumors, with 31 carcinomas, in 36/50 mice), but the activity disappeared on storage; while there was no carcinogenic activity in mice, in New Zealand albino rabbits the petroleum fractions alone produced considerable numbers of tumors. One application of DMBA, however, did increase tumor incidence and shorten the latent period. The hexane-eluted fraction of a methanolic extract of croton seeds (which had little vesicant activity), had all the promoting activity of the original croton oil; this could be demonstrated with uethan (20 mg/day ip for 5 days) as the initiator as well as with DMBA. In conclusion, the authors distinguish sharply between the promoting activity of compounds such as croton oil, which lead mostly to benign tumors (many of which regress spontaneously), and the additive effects of carcinogenic substances which may have a stimulatory effect on the second stage of carcinogenesis; for this additive carcinogenic effect, they suggest the term developing action. Other studies on croton oil are also reviewed.« less

Evidence of Bioactive Compounds from Vernonia polyanthes Leaves with Topical Anti-Inflammatory Potential

PubMed Central

Rodrigues, Kamilla C. M.; Chibli, Lucas A.; Santos, Bruna C. S.; Temponi, Vanessa S.; Pinto, Nícolas C. C.; Scio, Elita; Del-Vechio-Vieira, Glauciemar; Alves, Maria S.; Sousa, Orlando V.

2016-01-01

Vernonia polyanthes Less. (Asteraceae), popularly known as “assa-peixe”, is a plant species used in Brazilian traditional medicine for the treatment of cutaneous damage, cicatrization, inflammation, and rheumatism. Based on these ethnopharmacological findings, the current study evaluated the topical anti-inflammatory effects of the hexane (HEVP) and ethyl acetate (EAEVP) extracts from V. polyanthes leaves in experimental models of skin inflammation. Chemical characterization was carried out by HPLC–UV/DAD analysis. Anti-inflammatory activity was evaluated using Croton oil-, arachidonic acid (AA)-, phenol-, ethyl phenylpropiolate (EPP)-, and capsaicin-induced ear edema models in mice. Histopathological evaluation and measurements of myeloperoxidase (MPO) and N-acetyl-β-d-glucosaminidase (NAG) enzymes were also performed. Rutin, luteolin, and apigenin were identified in EAEVP. Topically applied HEVP and EAEVP significantly (p < 0.05, p < 0.01 or p < 0.001) reduced edema induced by five different irritants at the doses tested (0.1, 0.5 and 1.0 mg/ear). Histopathological analysis revealed a reduction of edema, inflammatory cell infiltration, and vasodilation. In addition, the enzymes activity (MPO and NAG) in the ear tissues was reduced by the topical treatment of HEVP and EAEVP (p < 0.05, p < 0.01 or p < 0.001). The results suggest that V. polyanthes leaves are effective against cutaneous damage, which support its traditional use and open up new possibilities for the treatment of skin disorders. PMID:27916942

Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

PubMed Central

Han, Hee-Soo; Shin, Ji-Sun; Inn, Kyung-Soo; Lee, Jang-Hoon; Park, Geonha

2017-01-01

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine. PMID:29348772

Histological case-control study of peeling-induced skin changes by different peeling agents in surgically subcutaneous undermined skin flaps in facelift patients.

PubMed

Gonser, P; Kaestner, S; Jaminet, P; Kaye, K

2017-11-01

A histological evaluation of peeling-induced skin changes in subcutaneous undermined preauricular facial skin flaps of nine patients was performed. There were three treatment groups: Trichloroacetic acid (TCA) 25%, TCA 40% and phenol/croton oil; one group served as control. Two independent evaluators determined the epidermal and dermal thickness and the depth of necrosis (micrometre). The percentual tissue damage due to the peeling was calculated, and a one-sample t-test for statistical significance was performed. On the basis of the histomorphological changes, peeling depth was classified as superficial, superficial-partial, deep-partial and full thickness chemical burn. The histological results revealed a progression of wound depth for different peeling agents without full thickness necrosis. TCA peels of up to 40% can be safely applied on subcutaneous undermined facial skin flaps without impairing the vascular patency, producing a predictable chemical burn, whereas deep peels such as phenol/croton oil peels should not be applied on subcutaneous undermined skin so as to not produce skin slough or necrosis by impairing vascular patency. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Curative effect of Amorphophallus paeoniifolius tuber on experimental hemorrhoids in rats.

PubMed

Dey, Yadu Nandan; Wanjari, Manish M; Kumar, Dharmendra; Lomash, Vinay; Jadhav, Ankush D

2016-11-04

Amorphophallus paeoniifolius (Dennst.) Nicolson (Family- Araceae) is a crop of south East Asian origin. In India, its tuber is widely used in ethnomedicinal practices by different tribes for the treatment of piles (hemorrhoids). The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats. The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue. Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties. Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Optimisation of Croton gratissimus Oil Extraction by n-Hexane and Ethyl Acetate Using Response Surface Methodology.

PubMed

Jiyane, Phiwe Charles; Tumba, Kaniki; Musonge, Paul

2018-04-01

The extraction of oil from Croton gratissimus seeds was studied using the three-factor five-level full-factorial central composite rotatable design (CCRD) of the response surface methodology (RSM). The effect of the three factors selected, viz., extraction time, extraction temperature and solvent-to-feed ratio on the extraction oil yield was investigated when n-hexane and ethyl acetate were used as extraction solvents. The coefficients of determination (R 2 ) of the models developed were 0.98 for n-hexane extraction and 0.97 for ethyl acetate extraction. These results demonstrated that the models developed adequately represented the processes they described. From the optimized model, maximum extraction yield obtained from n-hexane and ethyl acetate extraction were 23.88% and 23.25%, respectively. In both cases the extraction temperature and solvent-to-feed ratio were 35°C and 5 mL/g, respectively. In n-hexane extraction the maximum conditions were reached only after 6 min whereas in ethyl acetate extraction it took 20 min to get the maximum extraction oil yield. Oil extraction of Croton gratissimus seeds, in this work, favoured the use of n-hexane as an extraction solvent as it offered higher oil yields at low temperatures and reduced residence times.

Immuno-Modulatory and Anti-Inflammatory Effects of Dihydrogracilin A, a Terpene Derived from the Marine Sponge Dendrilla membranosa.

PubMed

Ciaglia, Elena; Malfitano, Anna Maria; Laezza, Chiara; Fontana, Angelo; Nuzzo, Genoveffa; Cutignano, Adele; Abate, Mario; Pelin, Marco; Sosa, Silvio; Bifulco, Maurizio; Gazzerro, Patrizia

2017-07-28

We assessed the immunomodulatory and anti-inflammatory effects of 9,11-dihydrogracilin A (DHG), a molecule derived from the Antarctic marine sponge Dendrilla membranosa . We used in vitro and in vivo approaches to establish DHG properties. Human peripheral blood mononuclear cells (PBMC) and human keratinocytes cell line (HaCaT cells) were used as in vitro system, whereas a model of murine cutaneous irritation was adopted for in vivo studies. We observed that DHG reduces dose dependently the proliferative response and viability of mitogen stimulated PBMC. In addition, DHG induces apoptosis as revealed by AnnexinV staining and downregulates the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), signal transducer and activator of transcription (STAT) and extracellular signal-regulated kinase (ERK) at late time points. These effects were accompanied by down-regulation of interleukin 6 (IL-6) production, slight decrease of IL-10 and no inhibition of tumor necrosis factor-alpha (TNF-α) secretion. To assess potential properties of DHG in epidermal inflammation we used HaCaT cells; this compound reduces cell growth, viability and migration. Finally, we adopted for the in vivo study the croton oil-induced ear dermatitis murine model of inflammation. Of note, topical use of DHG significantly decreased mouse ear edema. These results suggest that DHG exerts anti-inflammatory effects and its anti-edema activity in vivo strongly supports its potential therapeutic application in inflammatory cutaneous diseases.

Croton megalocarpus oil-fired micro-trigeneration prototype for remote and self-contained applications: experimental assessment of its performance and gaseous and particulate emissions

PubMed Central

Wu, Dawei; Roskilly, Anthony P.; Yu, Hongdong

2013-01-01

According to the International Energy Agency's World Energy Outlook 2011, 60 per cent of the population in Africa, some 587 million people, mostly in sub-Saharan Africa, lacked access to electricity in 2009. We developed a 6.5 kWe micro-trigeneration prototype, on the basis of internal combustion engine with pure Croton megalocarpus oil (CMO) fuelling, which configures a distributed energy system to generate power, heating and cooling from a single sustainable fuel source for remote users. Croton megalocarpus is an indigenous tree in East and South Africa which has recently attracted lots of interests as a biofuel source because of its high oil-yield rate. The direct and local use of CMO, instead of CMO biodiesel converted by the transesterification process, minimizes the carbon footprints left behind because of the simple fuel production of CMO. The experimental assessment proves that the prototype fuelled with CMO achieves similar efficiency as with diesel. Also, with the elevation of the oil injection temperature, the gaseous and particulate emissions of CMO could be ameliorated to some extent as improvement of the atomization in the spray and the combustion in the engine cylinder. PMID:24427514

A Standardized Composition Comprised of Extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis for Cellulite

PubMed Central

Yimam, Mesfin; Lee, Young-Chul; Jiao, Ping; Hong, Mei; Brownell, Lidia; Jia, Qi

2017-01-01

Background: Cellulite, characterized by changes in the skin morphology presented as dimpled or puckered skin appearance, is highly prevalent among postadolescent women. Cellulite management ranges from topical cream applications to invasive procedures. While some interventions showed improvements in physical appearances of affected areas, so far, none have reversed the condition to a full recovery. These unsuccessful measures signify the intricate nature of cellulite etiology highlighting its complexity leading to the possibility for a combination treatment approach to target multiple mechanisms. Materials and Methods: We screened our plant library for extracts that reduce cellular lipid accumulation, improve microcirculation, possess high total antioxidant capacity, significant anti-platelet aggregation, and anti-inflammatory activities using lipid accumulation assay in 3T3-L1 cells, Croton oil-induced hemorrhoid test in rats as a model for microcirculation, anti-platelet aggregation assay, nitric oxide (NO) inhibition assay, and 1,1-diphenyl-2-picrylhydrazyl assay. Results: Three known botanicals such as Rosemary officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as lead extracts in these tests. Treatment of 3T3 cell with A. squamosa at 1 μg/ml resulted in 68.8% reduction in lipid accumulation. In croton oil-induced hemorrhoid study, Z. clava-herculis reduced the recto-anus coefficient by 79.6% at 6 mg/kg indicating improvement in microcirculations. Similarly, R. officinalis caused inhibition of 82%, 71.8%, and 91.8% in platelet aggregation, NO production and free radical generation at 31.25 μg/ml, 6.2 μg/ml, and 40 μg/ml concentrations suggesting its anti-oxidant, and anti-inflammatory activities. Conclusions: Data depicted here suggest that formulation of these well-known botanicals at a specific ratio perhaps may yield a composition with a much wider spectrum of mechanisms of actions to impact the multiple pathways involved in cellulite onset, continuation, or exacerbations. SUMMARY Cellulite represents one of the main esthetic concerns of women with a likely cause of psychological insecurities. Its pathophysiology involves multiple pathways that include vascular, adipose tissues, inflammation, structural and physiological.Treatment strategies for cellulite comprises increasing microcirculation flow, reducing lipogenesis, promoting lipolysis, free radicals scavenging or formation reduction, anti-inflammation and other invasive procedures.We screened our plant library for extracts that reduces cellular lipid accumulation, improves microcirculation, possesses high total antioxidant capacity, inhibits platelet aggregation, and moderates inflammation.Botanical extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as leads and formulated to yield a standardized composition designated as UP1307 and suggested its usage for cellulite. Abbreviations Used: GMP: Good Manufacturing Practice; CA: Carnosic acid; NF-kB: nuclear factor-kB; HPLC: high-performance liquid chromatography; EtOH: Ethanol; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; SD: Sprague Dawley; RAC: recto-anus coefficient; LPS: Lipopolysaccharide; DPPH: 1,1-diphenyl-2-picryl-hydrazyl; TNF-α: tumor necrosis factor; NO: Nitric oxide PMID:29263624

An examination of the phenol-croton oil peel: Part II. The lay peelers and their croton oil formulas.

PubMed

Hetter, G P

2000-01-01

From the turn of the century, lay face peelers, known as "skinners," ran "beautifier" salons. Beginning in the 1920s, lay peelers were using croton oil-phenol formulas in Hollywood. These persons were renowned, made a good living, and treated many, if not most, of the leading "stars" of the day. They had a treatment, a "secret," that physicians did not. Physicians brought their own wives to the peelers for their expertise. The leading lay peel personalities from the 1920s through to our time are presented. The lay peelers dominated the field until the 1960s, when legal attacks on them, often directly instigated by the newly educated physician peelers, put them at a legal disadvantage. Nevertheless, there was considerable interaction with many plastic surgeons along the way. Some plastic surgeons came into possession of the techniques and some also into knowledge of the ingredients in a formula. The author has presented the recipes of four of the renowned lay peelers, two from Hollywood, Gradé and Kelsen, and two from Miami, Coopersmith and Maschek. These recipes all have 80 to 90 percent less croton oil than the "classic" Baker formula and, therefore, wound less deeply. The Hollywood formulas were used on many celebrities both inside and outside the film world from the 1920s to the early 1990s. These lay recipes are cumbersome to prepare. The author has simplified the preparation of these lay recipes by using USP liquid phenol instead of crystals. These simple formulas are provided in a table and are as easy to prepare as the Baker formula.

Infrared spectroscopic analysis of skin tumor of mice treated with several medicinal plants

PubMed Central

Ali, Huma; Dixit, Savita

2013-01-01

Objective To evaluate the differences between cancerous tissue, drug treated tissue and its corresponding normal tissue by infrared spectroscopic analysis. Methods Methanolic extracts of Azadirachta indica, Ocimum sanctum, Aloe barbandesis, Tinospora cordifolia and Triticum aestivum were assessed for the isolation and purification of active compound. After that, combine crude and combine isolated samples were prepared. Skin tumor was induced by topical application of 7, 12-dimethyl benz (a) anthracene and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of different drugs, it was administered at a concentration of 400 mg/kg body weight daily up to 16 weeks. Fourier transform infrared spectroscopy analysis was used to differentiate the drug treated tissues with the normal and cancerous tissue. In the present study, spectra of different tissues were recorded in the range of 400-4 000 cm−1. Results The results of the present study have shown that the remarkable difference exists between the IR spectra of normal, drugs treated and cancerous tissue in terms of frequencies and intensities of prominent bands of cellular biomolecules. Conclusions Fourier transform infrared spectroscopy analysis suggests the chemopreventive effect of above treated drugs and the best result was observed in combine crude sample and in combine isolated sample or synergistic effect of individual crude and isolated extract in 7, 12-dimethyl benz (a) anthracene croton oil induced skin carcinogenesis in Swiss albino mice.

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice.

PubMed

Borrelli, F; Capasso, R; Severino, B; Fiorino, F; Aviello, G; De Rosa, G; Mazzella, M; Romano, B; Capasso, F; Fasolino, I; Izzo, A A

2011-08-01

Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice. Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin. Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6)  mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6)  mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner. Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes. © 2011 Blackwell Publishing Ltd.

Essential oil of Croton Zehntneri attenuates lung injury in the OVA-induced asthma model.

PubMed

Serra, Daniel Silveira; Gomes, Maria Diana Moreira; Cavalcante, Francisco Sales Ávila; Leal-Cardoso, José Henrique

2018-02-13

Croton zehntneri Pax et Hoffm. is a Euphorbiaceae species, popularly known as "canela de cunhã," a native plant of northeastern Brazil, whose essential oil (EOCZ) shows relatively specific myorelaxant action for the smooth muscle of the airways and in the respiratory tract. Based on this information, EOCZ figures as a candidate for testing in the treatment of asthma, and the present study investigated the benefits of using EOCZ in an ovalbumin-induced asthma model. 48 male BALB/c mice were divided into six groups (n = 8). In the ST, SO100, and SO300 groups, mice were sensitized and challenged with saline, and then treated with 200 µL of 0.1% Tween 80, 100 mg/kg EOCZ and 300 mg/kg EOCZ, respectively. In the OT, OO100, and OO300 groups, mice were sensitized and challenged with OVA, and then treated with 200 µL of 0.1% Tween 80, 100 mg/kg EOCZ and 300 mg/kg EOCZ, respectively. Our results demonstrated significant changes in all respiratory mechanics variables analyzed between the OO300 and OT groups demonstrating the effectiveness of EOCZ to attenuate the OVA-induced lung injury. In addition, the use of EOCZ at a dose of 300 mg/kg showed an antioxidant effect and decreased inflammatory cells in the pulmonary parenchyma. In conclusion, our results demonstrated that EOCZ was able to improve the lesion in the respiratory system of mice subjected to OVA-induced asthma. The antioxidant action of EOCZ was likely the main mechanism of action in the reversal of this lesion, so more tests should be performed for its confirmation.

Chemical composition and modulation of bacterial drug resistance of the essential oil from leaves of Croton grewioides.

PubMed

de Medeiros, Vivianne Marcelino; do Nascimento, Yuri Mangueira; Souto, Augusto Lopes; Madeiro, Sara Alves Lucena; Costa, Vicente Carlos de Oliveira; Silva, Suellen Maria P M; Falcão Silva, Vivyanne Dos Santos; Agra, Maria de Fátima; de Siqueira-Júnior, José Pinto; Tavares, Josean Fechine

2017-10-01

The essential oil from leaves of Croton grewioides Baill was obtained by hydrodistillation using Clevenger apparatus, and its chemical composition was analyzed by GC-MS, where 18 compounds were identified, mostly as monoterpenes (55.56%) and sesquiterpenes (44.44%), in which the major constituent was the α-pinene (47.43%). The essential oil of Croton grewioides (EOCg) and its major compound (α-pinene) were evaluated as modulators of antibiotic resistance in strain SA-1199B and IS-58 of Staphylococcus aureus that overexpresses efflux protein. The minimum inhibitory concentrations (MICs) of the antibiotics were determined by the microdilution assay in the absence and in the presence of sub-inhibitory concentration of EOCg and α-pinene. Although the EOCg and α-pinene did not indicate relevant antibacterial activity in vitro, they acted as antibiotic resistance modulators, i.e., EOCg in combination with norfloxacin, reducted its MIC, by 64× whereas in combination with tetracycline it was observed a reduction of 4×. Additionally, it was observed a MIC reduction of tetracycline by 32×, when combined with α-pinene. The results suggest that EOCg and α-pinene modulate or even reverse bacterial resistance as a putative efflux pump inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemoprevention of skin cancer by the flavonoid fraction of Saraca asoka.

PubMed

Cibin, T R; Devi, D Gayathri; Abraham, Annie

2010-05-01

Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin carcinogenesis. Histological data also support the chemopreventive potential of S. asoka. Copyright (c) 2009 John Wiley & Sons, Ltd.

Elimination of deleterious effects of DMBA-induced skin carcinogenesis in mice by Syzygium cumini seed extract.

PubMed

Parmar, Jyoti; Sharma, Priyanka; Verma, Preeti; Sharma, Priyanka; Goyal, Pradeep K

2011-09-01

The inhibition of tumor incidence by hydro-alcoholic extract of S.cumini seed was evaluated in mice on two stage process of skin carcinogenesis induced by single application of 7, 12-dimethyl benz(a)anthracene (100 µg/100µl of acetone), and 2 weeks later promoted by repeated application of croton oil (1% acetone/thrice in a week) till the end of the experiment (i.e. 16 weeks). Oral administration of extract at a dose of 250mg/kg b.wt./day at the peri-initiational stage (i.e. 7 days before and 7 days after DMBA application), promotional stage (i.e. from the time of croton oil application) and at both the stages (i.e. 7 days prior to DMBA application & continued till the end of experiment) to the mice, recorded a significant reduction in tumor incidence to 37.5, 50 & 25% respectively in comparison to the carcinogen treated control, where tumor incidence was found as 100%. Tumor yield and Tumor burden were also significantly reduced by SCE. Similarly, the cumulative number of papillomas after 16 weeks was 68 in the control group, which was reduced to 15, 21 & 8 in the animals treated with the SCE continuously at peri-, post- and peri- & post- initiation stage respectively. A significant impairment was noticed in the levels of reduced glutathione, superoxide dismutase, catalase & protein and enhancement in LPO in liver and skin of carcinogen treated control mice as compared with vehicle treated mice. All such parameters were returned to near normal value by administration of SCE to DMBA treated mice. These results suggest a possible chemopreventive property of S.cumini against DMBA induced skin carcinogenesis in mice.

Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract.

PubMed

Sharma, Jyoti; Goyal, Pradeep K

2015-07-01

Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticancer and antioxidative potential of Panax ginseng against chemical-induced skin carcinogenesis in mammals. Skin tumors were induced in Swiss albino mice by a single topical application of 7,12-dimethylbenz(a)anthracene (100 μg/100 μL acetone) and, 2 wks later, promoted by repeated applications of croton oil (thrice in a wk in 1% acetone) till the end of the experiment (i.e., 16 wk). Hydroalcoholic ginseng root extract at a dose of 25 mg/kg body weight/d was orally administered at the peri-initiation, postinitiation, and peri-post-initiation stages. Ginseng root extract treatment caused a significant reduction in tumor incidence, cumulative number of tumors, tumor yield, and tumor burden, as compared to the 7,12-dimethylbenz(a)anthracene-croton oil-treated control group. Further, biochemical assays revealed a significant enhancement in the levels of reduced glutathione, superoxide dismutase, catalase, vitamin C, and total proteins but a significant reduction in lipid peroxidation levels in both the liver and skin with ginseng root extract treatment, as compared to carcinogen-treated control group. These results suggest that P. ginseng has the potential to become a pivotal chemopreventive agent that can reduce cancer in mammals.

Evidence of anti-inflammatory effect and percutaneous penetration of a topically applied fish oil preparation: a photoacoustic spectroscopy study

NASA Astrophysics Data System (ADS)

Ames, Franciele Q.; Sato, Francielle; de Castro, Lidiane V.; de Arruda, Laura L. M.; da Rocha, Bruno A.; Cuman, Roberto K. N.; Baesso, Mauro L.; Bersani-Amado, Ciomar A.

2017-05-01

This paper investigates the topical anti-inflammatory effect of a fish oil preparation (FOP) in a croton oil (CO) model of skin inflammation. The photoacoustic spectroscopy (PAS) was applied to estimate the percutaneous penetration of the FOP and as a model to evaluate the topical inflammatory response. After applying CO, the groups of mice received a topical application of a FOP on the left ear. The right ear received the vehicle that was used to dilute the CO. After 6 h, ear tissue was collected to determine the percent inhibition of edema, myeloperoxidase (MPO) activity, and cytokine levels and to perform PAS measurements. Treatment with FOP reduced edema and MPO activity, which was at least partially attributed to a decrease in the levels of tumor necrosis factor, interleukin-1β, interleukin-6, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. The topically applied FOP penetrated into the tissue and decreased the area of the bands that characterize inflamed tissue. The present results demonstrated the topical anti-inflammatory effect of the FOP. PAS suggests that FOP anti-inflammatory activity is linked with its ability to penetrate through the skin.

Chemopreventive effect of Lagenaria siceraria in two stages DMBA plus croton oil induced skin papillomagenesis.

PubMed

Kumar, Navneet; Kale, Raosaheb K; Tiku, Ashu B

2013-01-01

Cancer chemoprevention is a dietary or therapeutic strategy to prevent, suppress, or delay carcinogenesis either at initiation or progression level with nontoxic agents. Use of natural dietary compounds has been a major chemopreventive approach to modulate tumorigenic pathways. In the present study, we have evaluated Lagenaria siceraria (bottle gourd), a common vegetable of Indian household for its chemomodulatory potential. The fruit has been used in traditional medicine for a very long time for health benefits and to cure pain, ulcers, fever, cough, asthma, and other bronchial disorders. However, despite its reported beneficial effect the chemo modulatory potential of this plant has not been reported. Therefore chemopreventive effect of bottle gourd juice (BGJ) was studied against 7,12-dimethylbenz(a)anthracene (DMBA) plus croton oil induced skin papillomagenesis in Swiss albino mice. The effect was studied both at antiinitiation and antiinitiation/promotion level followed by histopathological study. A dose of 2.5% and 5% given in drinking water showed significant decrease in papilloma number, papilloma incidence, papilloma multiplicity, papilloma latency, papilloma volume, and papilloma size in different size range. Histopathological study showed chemopreventive effect by minimizing loss of stratification, a decrease in number of epithelial layers, reducing dermal infiltration and protection for various cytoplasmic changes. Higher dose of BGJ was found to be more effective than lower dose and the chemopreventive effect was maximum for antiinitiation/promotion treatment. Altogether, this study reports the chemopreventive effect of Lagenaria siceraria on skin papillomagenesis for the first time and suggests that its consumption may help in suppression of skin cancer.

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

PubMed

Dutta, Somit; Chakraborty, Arnab Kumar; Dey, Priyankar; Kar, Pallab; Guha, Pokhraj; Sen, Subhajit; Kumar, Anoop; Sen, Arnab; Chaudhuri, Tapas Kumar

2018-01-01

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above.

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

PubMed Central

Dutta, Somit; Chakraborty, Arnab Kumar; Dey, Priyankar; Kar, Pallab; Guha, Pokhraj; Sen, Subhajit; Kumar, Anoop; Sen, Arnab

2018-01-01

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above. PMID:29709010

Mosquito (Diptera: Culicidae) repellency field tests of essential oils from plants traditionally used in Laos.

PubMed

Vongsombath, Chanda; Pålsson, Katinka; Björk, Lars; Borg-Karlson, Anna-Karin; Jaenson, Thomas G T

2012-11-01

Essential oils of Hyptis suaveolens (Lamiaceae), Croton roxburghii (Euphorbiaceae), and Litsea cubeba (Lauraceae) were tested in the field near Vientiane city, Lao PDR, on humans for repellent activity against mosquitoes. Landing mosquitoes were collected and later identified. The most abundant mosquitoes captured belonged to the genera Armigeres, Culex, and Aedes. All the plant oils tested at concentrations of 1.7 microg/cm(2), 3.3 microg/cm(2), and 6.3 microg/cm(2) were significantly more mosquito repellent than the negative control. Croton oil was significantly repellent against mosquitoes of the three genera at the highest (6.3 microg/cm(2)) concentration tested. Litsea oil was significantly repellent against Armigeres at all (1.7 microg/cm(2), 3.3 microg/cm(2), and 6.3 microg/cm(2)) concentrations tested. Hyptis oil was significantly repellent against Armigeres at 3.3 microg/cm(2) and 6.3 microg/cm(2) and against Culex at 1.7 microg/cm(2) and 6.3 microg/cm(2). The oils were analyzed for chemical content of volatiles, mainly terpenes. Main constituents were beta-pinene, sabinene, and 1,8-cineol from oils of the green parts of H. suaveolens; alpha-pinene, beta-pinene, and alpha-phellandrene from fresh bark of C. roxburghii; and alpha-pinene, beta-phellandrene, sabinene, and 1,8-cineol from fresh fruits of L. cubeba.

Anthelmintic activity of Croton zehntneri and Lippia sidoides essential oils.

PubMed

Camurça-Vasconcelos, A L F; Bevilaqua, C M L; Morais, S M; Maciel, M V; Costa, C T C; Macedo, I T F; Oliveira, L M B; Braga, R R; Silva, R A; Vieira, L S

2007-09-30

Because of the development of anthelmintic resistant populations, the search for new drugs is essential to maintain the productivity of small ruminants. The aim of this study was to evaluate the anthelmintic activity of Croton zehntneri and Lippia sidoides essential oils and their major constituents, anethole and thymol. The effects of these oils and their constituents were determined by in vitro assays with the eggs and larvae of the sheep gastrointestinal nematode Haemonchus contortus. The two essential oils were evaluated on intestinal nematodes of mice at 800 mg kg(-1) dose. In the last experiment, the mice were treated with larger doses of L. sidoides, 1200 and 1600 mg kg(-1). The essential oils and their constituents prevented more than 98% of the H. contortus eggs from hatching at a concentration of 1.25 mg ml(-1) and inhibited more than 90% of H. contortus larval development at a concentration of 10 mg ml(-1). At a concentration of 800 mg kg(-1), the two essential oils were 46.3% and 11.64% effective against Syphacia obvelata and Aspiculuris tetraptera. At 1200 and 1600 mg kg(-1), L. sidoides essential oil's efficacy on the mouse worm burden was 57.6% and 68.9%, respectively. The fact that L. sidoides essential oil was almost 70% effective against mouse intestinal nematodes indicates it should be evaluated against gastrointestinal nematodes of sheep and goats.

Treatment with Aqueous Extract from Croton cajucara Benth Reduces Hepatic Oxidative Stress in Streptozotocin-Diabetic Rats

PubMed Central

Rodrigues, Graziella Ramos; Di Naso, Fábio Cangeri; Porawski, Marilene; Marcolin, Éder; Kretzmann, Nélson Alexandre; Ferraz, Alexandre de Barros Falcão; Richter, Marc Francois; Marroni, Cláudio Augusto; Marroni, Norma Possa

2012-01-01

Croton cajucara Benth is a plant found in Amazonia, Brazil and the bark and leaf infusion of this plant have been popularly used to treat diabetes and hepatic disorders. The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Croton cajucara Benth (1.5 mL of the C. cajucara extract i.g.) in rats with streptozotocin-induced diabetes. Croton cajucara Benth was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipid peroxidation and superoxide dismutase, catalase, and glutathione reductase activities were measured in the hepatic tissue, as well as the presence activation of p65 (NF-κB), through western blot. Phytochemical screening of Croton cajucara Benth detected the presence of flavonoids, coumarins and alkaloids. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hypoxanthine/xanthine oxidase assays. Liver lipid peroxidation increased in diabetic animals followed by a reduction in the Croton-cajucara-Benth-treated group. There was activation of p65 nuclear expression in the diabetic animals, which was attenuated in the animals receiving the Croton cajucara Benth aqueous extract. The liver tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. In conclusion the Croton cajucara Benth aqueus extract treatment effectively reduced the oxidative stress and contributed to tissue recovery. PMID:22811599

Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved.

PubMed

Oliveira Júnior, Raimundo Gonçalves de; Ferraz, Christiane Adrielly Alves; Silva, Juliane Cabral; de Andrade Teles, Roxana Braga; Silva, Mariana Gama; Diniz, Tâmara Coimbra; Dos Santos, Uiliane Soares; de Souza, Ana Valéria Vieira; Nunes, Carlos Eduardo Pereira; Salvador, Marcos José; Lorenzo, Vitor Prates; Quintans Júnior, Lucindo José; Almeida, Jackson Roberto Guedes da Silva

2018-07-15

Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p < 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole - 21.42%, spathulenol - 15.47%, p-cymene - 12.41% and caryophyllene oxide - 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p < 0.05), indicating possible involvement of GABA A receptors. Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used. Copyright © 2018 Elsevier B.V. All rights reserved.

Ozone-Induced Vascular Contractility and Pulmonary Injury Are Differentially Impacted by Diets Enriched With Coconut Oil, Fish Oil, and Olive Oil.

PubMed

Snow, Samantha J; Cheng, Wan-Yun; Henriquez, Andres; Hodge, Myles; Bass, Virgina; Nelson, Gail M; Carswell, Gleta; Richards, Judy E; Schladweiler, Mette C; Ledbetter, Allen D; Chorley, Brian; Gowdy, Kymberly M; Tong, Haiyan; Kodavanti, Urmila P

2018-05-01

Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.

Radical scavenging and antimicrobial activities of Croton zehntneri, Pterodon emarginatus and Schinopsis brasiliensis essential oils and their major constituents: estragole, trans-anethole, β-caryophyllene and myrcene.

PubMed

Donati, Maddalena; Mondin, Andrea; Chen, Zheng; Miranda, Fabricio Mendes; do Nascimento, Baraquizio Braga; Schirato, Giulia; Pastore, Paolo; Froldi, Guglielmina

2015-01-01

The essential oils (EOs) from the Brazilian species Croton zehntneri, Pterodon emarginatus and Schinopsis brasiliensis were examined for their chemical constituents, and antioxidant and antimicrobial activities. The composition of EOs was determined by using gas chromatography coupled with mass spectrometry analysis, while the antioxidant activity was evaluated through the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays. Furthermore, the antimicrobial activity was investigated against Escherichia coli and Pseudomonas aeruginosa (both Gram-negative), Staphylococcus aureus (Gram-positive) and Candida parapsilosis (fungus). The main components of C. zehntneri, P. emarginatus and S. brasiliensis were identified as estragole, trans-anethole, β-caryophyllene and myrcene. Among the EOs, P. emarginatus showed the highest antioxidant activity, with an IC50 of 7.36 mg/mL and a Trolox equivalent antioxidant capacity of 3748 μmol/g determined by DPPH and ORAC assays, respectively. All EOs showed low activities against the bacterial strains tested, whereas the C. zehntneri oil and its main constituent estragole exhibited an appreciable antifungal activity against C. parapsilosis.

Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.

PubMed

De Petrocellis, L; Orlando, P; Moriello, A Schiano; Aviello, G; Stott, C; Izzo, A A; Di Marzo, V

2012-02-01

Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other 'thermo-TRP's', the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract. TRP activity was assessed by evaluating elevation of [Ca(2+)](i) in rat recombinant TRPV3- and TRPV4-expressing HEK-293 cells. TRP channel mRNA expression was measured by quantitative RT-PCR in the jejunum and ileum of mice treated with vehicle or the pro-inflammatory agent croton oil. (i) CBD and tetrahydrocannabivarin (THCV) stimulated TRPV3-mediated [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and potency (EC(50∼) 3.7 μm), whereas cannabigerovarin (CBGV) and cannabigerolic acid (CBGA) were significantly more efficacious at desensitizing this channel to the action of carvacrol than at activating it; (ii) cannabidivarin and THCV stimulated TRPV4-mediated [Ca(2+)](i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC(50) 0.9-6.4 μm), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-α-phorbol 12,13-didecanoate (4α-PDD) than at activating it; (iii) CBC reduced TRPV1β, TRPV3 and TRPV4 mRNA in the jejunum, and TRPV3 and TRPV4 mRNA in the ileum of croton oil-treated mice. Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

Essential oil of Croton zehntneri and its main constituent anethole block excitability of rat peripheral nerve.

PubMed

da Silva-Alves, Kerly Shamyra; Ferreira-da-Silva, Francisco Walber; Coelho-de-Souza, Andrelina Noronha; Albuquerque, Aline Alice Cavalcante; do Vale, Otoni Cardoso; Leal-Cardoso, José Henrique

2015-03-01

Croton zehntneri is an aromatic plant native to Northeast Brazil and employed by local people to treat various diseases. The leaves of this plant have a rich content of essential oil. The essential oil of C. zehntneri samples, with anethole as the major constituent and anethole itself, have been reported to have several pharmacological activities such as antispasmodic, cardiovascular, and gastroprotective effects and inducing the blockade of neuromuscular transmission and antinociception. Since several works have demonstrated that essential oils and their constituents block cell excitability and in view of the multiple effects of C. zehntneri essential oil and anethole on biological tissues, we undertook this investigation aiming to characterize and compare the effects of this essential oil and its major constituent on nerve excitability. Sciatic nerves of Wistar rats were used. They were mounted in a moist chamber, and evoked compound action potentials were recorded. Nerves were exposed in vitro to the essential oil of C. zehntneri and anethole (0.1-1 mg/mL) up to 180 min, and alterations in excitability (rheobase and chronaxie) and conductibility (peak-to-peak amplitude and conduction velocity) parameters of the compound action potentials were evaluated. The essential oil of C. zehntneri and anethole blocked, in a concentration-dependent manner with similar pharmacological potencies (IC50: 0.32 ± 0.07 and 0.22 ± 0.11 mg/mL, respectively), rat sciatic nerve compound action potentials. Strength-duration curves for both agents were shifted upward and to the right compared to the control curve, and the rheobase and chronaxie were increased following essential oil and anethole exposure. The time courses of the essential oil of C. zehntneri and anethole effects on peak-to-peak amplitude of compound action potentials followed an exponential decay and reached a steady state. The essential oil of C. zehntneri and anethole caused a similar reduction in conduction velocities of the compound action potential waves investigated. In conclusion, we demonstrated here that the essential oil of C. zehntneri blocks neuronal excitability and that this effect, which can be predominantly attributable to its major constituent, anethole, is important since these agents have several pharmacological effects likely related to the alteration of excitability. This finding is relevant due to the use of essential oils in aromatherapy and the low acute toxicity of this agent, which exhibits other effects of potential therapeutic usefulness. Georg Thieme Verlag KG Stuttgart · New York.

Toxicological Evaluation of Essential Oil From the Leaves of Croton argyrophyllus (Euphorbiaceae) on Aedes aegypti (Diptera: Culicidae) and Mus musculus (Rodentia: Muridae).

PubMed

Cruz, R C D; Silva, S L C E; Souza, I A; Gualberto, S A; Carvalho, K S; Santos, F R; Carvalho, M G

2017-07-01

Plant-derived essential oils can be used as insecticides for vector control. However, to establish their safety, it is necessary to perform toxicological studies. Herein, we evaluated the chemical composition and insecticidal activity of the essential oil from the leaves of Croton argyrophyllus on the third- and fourth-instar larvae and adult Aedes aegypti (L., 1762). We also evaluated the acute toxicity of the essential oil in adult female Mus musculus. The lethal concentration 50 (LC50) and 90 (LC90) of C. argyrophyllus essential oil on larvae of Ae. aegypti were 0.31 and 0.70 mg ml-1, respectively, and 5.92 and 8.94 mg ml-1, respectively, on Ae. aegypti adults. The major components of the essential oil were spathulenol (22.80%), (E)-caryophyllene (15.41%), α-pinene (14.07%), and bicyclogermacrene (10.43%). It also displayed acute toxicity in adults of Mus musculus; the intraperitoneal and oral lethal dose 50 (LD50) were 2,000 mg kg-1 and 2,500 mg kg-1, respectively. The results showed that the essential oil from C. argyrophyllus leaves has insecticidal activity on Ae. aegypti larvae and adults at an average lethal concentration below the median lethal dose needed to cause acute toxicity in the common mouse. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analysis of the Potential Topical Anti-Inflammatory Activity of Averrhoa carambola L. in Mice

PubMed Central

Cabrini, Daniela Almeida; Moresco, Henrique Hunger; Imazu, Priscila; da Silva, Cíntia Delai; Pietrovski, Evelise Fernandes; Mendes, Daniel Augusto Gasparin Bueno; Prudente, Arthur da Silveira; Pizzolatti, Moacir Geraldo; Brighente, Inês Maria Costa; Otuki, Michel Fleith

2011-01-01

Inflammatory skin disorders, such as psoriasis and atopic dermatitis, are very common in the population; however, the treatments currently available are not well tolerated and are often ineffective. Averrhoa carambola L. (Oxalidaceae) is an Asian tree that has been used in traditional folk medicine in the treatment of several skin disorders. The present study evaluates the topical anti-inflammatory effects of the crude ethanolic extract of A. carambola leaves, its hexane, ethyl acetate, and butanol fractions and two isolated flavonoids on skin inflammation. Anti-inflammatory activity was measured using a croton oil-induced ear edema model of inflammation in mice. Topically applied ethanolic extract reduced edema in a dose-dependent manner, resulting in a maximum inhibition of 73 ± 3% and an ID50 value of 0.05 (range: 0.02–0.13) mg/ear. Myeloperoxidase (MPO) activity was also inhibited by the extract, resulting in a maximum inhibition of 60 ± 6% (0.6 mg/ear). All of the fractions tested caused inhibition of edema formation and of MPO activity. Treatment with the ethyl acetate fraction was the most effective, resulting in inhibition levels of 75 ± 5 and 54 ± 8% for edema formation and MPO activity, respectively. However, treatment of mice with isolated compounds [apigenin-6-C-β-l-fucopyranoside and apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-β-l-fucopyranoside] did not yield successful results. Apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-β-l-fucopyranoside caused only a mild reduction in edema formation (28 ± 11%). Taken together, these preliminary results support the popular use of A. carambola as an anti-inflammatory agent and open up new possibilities for its use in skin disorders. PMID:21785638

Analysis of the Potential Topical Anti-Inflammatory Activity of Averrhoa carambola L. in Mice.

PubMed

Cabrini, Daniela Almeida; Moresco, Henrique Hunger; Imazu, Priscila; da Silva, Cíntia Delai; Pietrovski, Evelise Fernandes; Mendes, Daniel Augusto Gasparin Bueno; da Silveira Prudente, Arthur; Pizzolatti, Moacir Geraldo; Brighente, Inês Maria Costa; Otuki, Michel Fleith

2011-01-01

Inflammatory skin disorders, such as psoriasis and atopic dermatitis, are very common in the population; however, the treatments currently available are not well tolerated and are often ineffective. Averrhoa carambola L. (Oxalidaceae) is an Asian tree that has been used in traditional folk medicine in the treatment of several skin disorders. The present study evaluates the topical anti-inflammatory effects of the crude ethanolic extract of A. carambola leaves, its hexane, ethyl acetate, and butanol fractions and two isolated flavonoids on skin inflammation. Anti-inflammatory activity was measured using a croton oil-induced ear edema model of inflammation in mice. Topically applied ethanolic extract reduced edema in a dose-dependent manner, resulting in a maximum inhibition of 73 ± 3% and an ID(50) value of 0.05 (range: 0.02-0.13) mg/ear. Myeloperoxidase (MPO) activity was also inhibited by the extract, resulting in a maximum inhibition of 60 ± 6% (0.6 mg/ear). All of the fractions tested caused inhibition of edema formation and of MPO activity. Treatment with the ethyl acetate fraction was the most effective, resulting in inhibition levels of 75 ± 5 and 54 ± 8% for edema formation and MPO activity, respectively. However, treatment of mice with isolated compounds [apigenin-6-C-β-l-fucopyranoside and apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-β-l-fucopyranoside] did not yield successful results. Apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-β-l-fucopyranoside caused only a mild reduction in edema formation (28 ± 11%). Taken together, these preliminary results support the popular use of A. carambola as an anti-inflammatory agent and open up new possibilities for its use in skin disorders.

Anti-inflammatory activity of methanol extract and n-hexane fraction mojabanchromanol b from Myagropsis myagroides.

PubMed

Jeong, Da-Hyun; Kim, Koth-Bong-Woo-Ri; Kim, Min-Ji; Kang, Bo-Kyeong; Ahn, Dong-Hyun

2014-09-26

This study was carried out to verify the anti-inflammatory effect of methanol extract from Myagropsis myagroides (MMME) and its n-hexane fraction mojabanchromanol b. The murine macrophages Raw264.7 cells were used. The pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and the expression of iNOS, COX-2, and NF-κB p65 were examined by ELISA and immunoblotting. To investigate the inhibitory effect of MMME in an animal model of inflammation, an assay to determine croton oil-induced ear edema in mice was performed. NO levels decreased with increasing concentration of MMME, and were inhibited up to 50%. The secretion of IL-6, TNF-α, and IL-1β was suppressed in a dose-dependent manner, especially at 50μg/mL, inhibition activities of cytokines were over 50%. MMME also suppressed the expression of COX-2, iNOS, and NF-κB p65, suggesting that MMME could affect the expression of inflammation related cytokines and proteins through the deregulation of NF-κB. Moreover, the formation of mouse ear edema was reduced at the highest dose tested compared to that in the control, and generated similar effects compared with prednisolone at 250mg/kg in mice ear edema evaluation test. In addition, the results in photomicrograph of mice ear tissue and mast cells also showed the same effect. After purification of fractions of MMME, it indicated that n-hexane fraction mojabanchromanol b was the most active fraction showing the inhibitory effect of IL-6 and TNF-α. These results suggested that MMME and mojabanchromanol b may have great effects on inflammatory factors and be potential anti-inflammatory therapeutic materials. Copyright © 2014 Elsevier Inc. All rights reserved.

Topical anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica.

PubMed

Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A; Martínez-Vitela, Carlos; Serna-Saldívar, Sergio O

2015-01-01

Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO production in vitro (73.5 ± 4.8% and 68.7 ± 5.0%, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4 ± 5.7%) equating the indomethacin effects (69.5 ± 5.3%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient.

Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis.

PubMed

Scholzen, T E; Steinhoff, M; Bonaccorsi, P; Klein, R; Amadesi, S; Geppetti, P; Lu, B; Gerard, N P; Olerud, J E; Luger, T A; Bunnett, N W; Grady, E F; Armstrong, C A; Ansel, J C

2001-01-15

Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP(-/-) knockout and NEP(+/+) wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP(-/-) animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP(-/-) mice, the acute inhibition of NEP in NEP(+/+) animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP(-/-) compared with NEP(+/+) animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.

Topical Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated from Opuntia ficus-indica

PubMed Central

Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A.; Martínez-Vitela, Carlos; Serna-Saldívar, Sergio O.

2015-01-01

Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO production in vitro (73.5 ± 4.8% and 68.7 ± 5.0%, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4 ± 5.7%) equating the indomethacin effects (69.5 ± 5.3%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient. PMID:25821823

Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response

PubMed Central

Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Cassarotti, Larissa Laila; Salvadego, Valter Eduardo Cocco; Spironello, Ricardo Alexandre; Bersani-Amado, Ciomar Aparecida

2018-01-01

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 μg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine. PMID:29743918

Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.

PubMed

Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo

2016-02-01

Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.

Improvement of skin condition in striae distensae: development, characterization and clinical efficacy of a cosmetic product containing Punica granatum seed oil and Croton lechleri resin extract

PubMed Central

Bogdan, Cătălina; Iurian, Sonia; Tomuta, Ioan; Moldovan, Mirela

2017-01-01

Striae distensae are a frequent skin condition associated with pregnancy, weight change or lack of skin elasticity. The aim of this research was to obtain a topical product containing herbal active ingredients with documented antioxidant and anti-inflammatory activity (Punica granatum seed oil and Croton lechleri resin extract) and demonstrate its positive effect on prevention and treatment of striae distensae. First, the cream base formulation was optimized through experimental design. Secondly, the cream containing the two active ingredients was investigated in an interventional nonrandomized clinical trial. The clinical outcome was assessed through biophysical parameters and ultrasonographic evaluation. The state of the skin was evaluated by biophysical measurements and ultrasonography at the beginning of the study and after 3 and 6 weeks. The experimental design was successfully used to set the best ranges for the technological and formulation factors to obtain a cosmetic formulation with optimal characteristics. The study of clinical efficacy on the optimal formulation revealed an increase in the dermis thickness, hydration and elasticity values in both groups after 6 weeks of cream application. The new oil-in-water cream containing P. granatum seed oil and C. lechleri resin extract can be helpful in the prevention or improving of skin changes associated with striae. PMID:28280300

Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Essential Oil from Leaves of Mentha piperita Grown in China

PubMed Central

Wang, Jing; Zhou, Lianming; Yang, Peiming

2014-01-01

The chemical composition, anti-inflammatory, cytotoxic and antioxidant activities of essential oil from leaves of Mentha piperita (MEO) grown in China were investigated. Using GC-MS analysis, the chemical composition of MEO was characterized, showing that it was mainly composed of menthol, menthone and menthy acetate. MEO exhibited potent anti-inflammatory activities in a croton oil-induced mouse ear edema model. It could also effectively inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The cytotoxic effect was assessed against four human cancer cells. MEO was found to be significantly active against human lung carcinoma SPC-A1, human leukemia K562 and human gastric cancer SGC-7901 cells, with an IC50 value of 10.89, 16.16 and 38.76 µg/ml, respectively. In addition, MEO had moderate antioxidant activity. The results of this study may provide an experimental basis for further systematic research, rational development and clinical utilization of peppermint resources. PMID:25493616

Chemical Composition and Anti-Inflammatory, Cytotoxic and Antioxidant Activities of Essential Oil from Leaves of Mentha piperita Grown in China.

PubMed

Sun, Zhenliang; Wang, Huiyan; Wang, Jing; Zhou, Lianming; Yang, Peiming

2014-01-01

The chemical composition, anti-inflammatory, cytotoxic and antioxidant activities of essential oil from leaves of Mentha piperita (MEO) grown in China were investigated. Using GC-MS analysis, the chemical composition of MEO was characterized, showing that it was mainly composed of menthol, menthone and menthy acetate. MEO exhibited potent anti-inflammatory activities in a croton oil-induced mouse ear edema model. It could also effectively inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The cytotoxic effect was assessed against four human cancer cells. MEO was found to be significantly active against human lung carcinoma SPC-A1, human leukemia K562 and human gastric cancer SGC-7901 cells, with an IC50 value of 10.89, 16.16 and 38.76 µg/ml, respectively. In addition, MEO had moderate antioxidant activity. The results of this study may provide an experimental basis for further systematic research, rational development and clinical utilization of peppermint resources.

Dietary olive oil induces cannabinoid CB2 receptor expression in adipose tissue of ApcMin/+ transgenic mice

PubMed Central

Notarnicola, Maria; Tutino, Valeria; Tafaro, Angela; Bianco, Giusy; Guglielmi, Emilia; Caruso, Maria Gabriella

2016-01-01

BACKGROUND: Cannabinoid- 2 (CB2) receptor is known for its anti-obesity effects silencing the activated immune cells that are key drivers of metabolic syndrome and inflammation. Nutritional interventions in experimental models of carcinogenesis have been demonstrated to modulate tissue inflammation state and proliferation. OBJECTIVE: Aim of this study was to test, in ApcMin/+ mice, whether a diet enriched with olive oil, omega- 3 and omega-6- PUFAs affects the adipose tissue inflammation status. METHODS: Four groups of animal were studied: ST group, receiving a standard diet; OO group, receiving the standard diet in which soybean oil (source of fats) was replaced with olive oil; OM-3 group, receiving the standard diet in which soybean oil was replaced with salmon oil; OM-6 group, receiving the standard diet in which soybean oil was replaced with oenothera oil. Gene and protein expression, in adipose tissue, were evaluated by RT-PCR and Western Blotting, respectively. Enzymatic activities were assayed by fluorescent and radiometric method, where appropriated. RESULTS: The diet enriched with olive oil significantly induced CB2 receptor expression and it was able to control inflammatory and proliferative activity of mice adipose tissue. CONCLUSIONS: The present findings open opportunities for developing novel nutritional strategies considering olive oil a key ingredient of a healthy dietary pattern. PMID:28035344

Antiinflammatory effect of Japanese horse chestnut (Aesculus turbinata) seeds.

PubMed

Sato, Itaru; Kofujita, Hisayoshi; Suzuki, Tadahiko; Kobayashi, Haruo; Tsuda, Shuji

2006-05-01

The antiinflammatory effects of Japanese horse chestnut (Aesculus turbinata) seeds were examined in vivo and in vitro. The extract of this seed (HCSE) inhibited croton oil-induced swelling of the mouse concha. HCSE inhibited cyclooxygenase (COX) -1 and -2 activities, but had no effect on 15-lipoxygenase and phospholipase A2 activities. Inhibition of COX-2 occurred at a lower concentration of HCSE than for COX-1. Japanese horse chestnut seeds contain coumarins and saponins, but these chemicals did not inhibit COX activities. These results suggest that the antiinflammatory effect of Japanese horse chestnut seeds is caused, at least partly, by the inhibition of COX. The inhibitor of COX in this seed may be a chemical(s) other than coumarins and saponins.

Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis.

PubMed

Elgebaly, Hassan A; Mosa, Nermeen M; Allach, Mariam; El-Massry, Khaled F; El-Ghorab, Ahmed H; Al Hroob, Amir M; Mahmoud, Ayman M

2018-02-01

Olive oil and leaf extract have several health benefits; however, their beneficial effect against fluoxetine-induced liver injury has not been investigated. The present study aimed to scrutinize the impact of fluoxetine on the liver of rats and to evaluate the protective effects of olive oil and leaf extract. Rats received fluoxetine orally at dose of 10 mg/kg body weight for 7 consecutive days. The fluoxetine-induced rats were concurrently treated with olive oil or leaf extract. At the end of the experiment, blood and liver samples were collected for analysis. Fluoxetine administration significantly increased circulating ALT, AST, ALP and the pro-inflammatory cytokines TNF-α and IL-1β levels in rats. Histological analysis showed several alterations, such as inflammatory cells infiltration, hepatocyte vacuolation and dilated sinusoids in the liver of fluoxetine-induced rats. Concurrent supplementation of olive oil and olive leaf extract significantly reduced circulating liver function marker enzymes and pro-inflammatory cytokines, and prevented fluoxetine-induced histological alterations. Both olive oil and leaf extract significantly decreased liver lipid peroxidation and nitric oxide, and ameliorated liver glutathione, superoxide dismutase, catalase and glutathione peroxidase. In addition, olive oil and leaf extract prevented fluoxetine-induced apoptosis in the liver of rats as evidenced by decreased expression of Bax and caspase-3, and up-regulated expression of Bcl-2. In conclusion, olive oil and leaf extract protect against fluoxetine-induced liver injury in rats through attenuation of oxidative stress, inflammation and apoptosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Ethnopharmacological Uses, Phytochemistry, and Pharmacological Properties of Croton macrostachyus Hochst. Ex Delile: A Comprehensive Review

PubMed Central

2017-01-01

Croton macrostachyus is widely used as herbal medicine by the indigenous people of tropical Africa. The potential of C. macrostachyus as herbal medicine, the phytochemistry, and pharmacological properties of its parts used as herbal medicines are reviewed. The extensive literature survey revealed that C. macrostachyus is traditionally used to treat or manage at least 81 human and animal diseases and ailments. The species is used as herbal medicine for diseases and ailments such as abdominal pains, cancer, gastrointestinal disorders, malaria, pneumonia, sexually transmitted infections, skin infections, typhoid, and wounds and as ethnoveterinary medicine. Multiple classes of phytochemicals such as alkaloids, amino acids, anthraquinones, carbohydrates, cardiac glycosides, coumarins, essential oil, fatty acids, flavonoids, phenolic compounds, phlobatannins, polyphenols, phytosteroides, saponins, sterols, tannins, terpenoids, unsaturated sterol, vitamin C, and withanoides have been isolated from the species. Pharmacological studies on C. macrostachyus indicate that it has a wide range of pharmacological activities such as anthelmintic, antibacterial, antimycobacterial, antidiarrhoeal, antifungal, anticonvulsant and sedative, antidiabetic, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, and larvicidal effects. Croton macrostachyus has potential as a possible source of a wide range of pharmaceutical products for the treatment of a wide range of both human and animal diseases and ailments. PMID:29234365

Phytochemical Analysis and Antimicrobial, Antinociceptive, and Anti-Inflammatory Activities of Two Chemotypes of Pimenta pseudocaryophyllus (Myrtaceae)

PubMed Central

de Paula, Joelma Abadia Marciano; Silva, Maria do Rosário Rodrigues; Costa, Maysa P.; Diniz, Danielle Guimarães Almeida; Sá, Fabyola A. S.; Alves, Suzana Ferreira; Costa, Élson Alves; Lino, Roberta Campos; de Paula, José Realino

2012-01-01

Preparations from Pimenta pseudocaryophyllus (Gomes) L.R. Landrum (Myrtaceae) have been widely used in Brazilian folk medicine. This study aims to evaluate the antimicrobial activity of the crude ethanol extracts, fractions, semipurified substances, and essential oils obtained from leaves of two chemotypes of P. pseudocaryophyllus and to perform the antinociceptive and anti-inflammatory screening. The ethanol extracts were purified by column chromatography and main compounds were spectrally characterised (1D and 2D 1H and 13C NMR). The essential oils constituents were identified by GC/MS. The broth microdilution method was used for testing the antimicrobial activity. The abdominal contortions induced by acetic acid and the ear oedema induced by croton oil were used for screening of antinociceptive and anti-inflammatory activities, respectively. The phytochemical analysis resulted in the isolation of pentacyclic triterpenes, flavonoids, and phenol acids. The oleanolic acid showed the best profile of antibacterial activity for Gram-positive bacteria (31.2–125 μg mL−1), followed by the essential oil of the citral chemotype (62.5–250 μg mL−1). Among the semipurified substances, Ppm5, which contained gallic acid, was the most active for Candida spp. (31.2 μg mL−1) and Cryptococcus spp. (3.9–15.6 μg mL−1). The crude ethanol extract and fractions from citral chemotype showed antinociceptive and anti-inflammatory effects. PMID:23082081

Dragon's blood Croton palanostigma induces genotoxic effects in mice.

PubMed

Maistro, Edson Luis; Ganthous, Giulia; Machado, Marina da Silva; Zermiani, Tailyn; Andrade, Sérgio Faloni de; Rosa, Paulo Cesar Pires; Perazzo, Fabio Ferreira

2013-05-20

Dragon's blood is a dark-red sap produced by species from the genus Croton (Euphorbiaceae), which has been used as a famous traditional medicine since ancient times in many countries, with scarce data about its safe use in humans. In this research, we studied genotoxicity and clastogenicity of Croton palanostigma sap using the comet assay and micronucleus test in cells of mice submitted to acute treatment. HPLC analysis was performed to identify the main components of the sap. The sap was administered by oral gavage at doses of 300 mg/kg, 1,000 mg/kg and 2,000 mg/kg. For the analysis, the comet assay was performed on the leukocytes and liver cells collected 24h after treatment, and the micronucleus test (MN) on bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The alkaloid taspine was the main compound indentified in the crude sap of Croton palanostigma. The results of the genotoxicity assessment show that all sap doses tested produced genotoxic effects in leukocytes and liver cells and also produced clastogenic/aneugenic effects in bone marrow cells of mice at the two higher doses tested. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution in the use of Croton palanostigma sap by humans considering its risk of carcinogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The essential oil from Citrus limetta Risso peels alleviates skin inflammation: In-vitro and in-vivo study.

PubMed

Maurya, Anil Kumar; Mohanty, Shilpa; Pal, Anirban; Chanotiya, Chandan Singh; Bawankule, Dnyaneshawar Umrao

2018-02-15

Citrus fruit peels are traditionally used in folk medicine for the treatment of skin disorders but it lacks proper pharmacological intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit crops used by juice processing industries in all continents. Ethnopharmacological validation of an essential oil isolated from its peels may play a key role in converting the fruit waste materials into therapeutic value added products. To evaluate the chemical and pharmacological (in-vitro and in-vivo) profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin inflammation for its ethnopharmacological validation. Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. Chemical fingerprint of Clp-EO revealed the presence of monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp-EO to the macrophages was able to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in LPS-induced inflammation as well as the production of reactive oxygen species (ROS) in H 2 O 2 -induced oxidative stress. In in-vivo study, topical application of Clp-EO was also able to reduce the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid peroxidation, pro-inflammatory cytokines production and ameliorate the histological damage in the ear tissue. In-vitro and in-vivo toxicity study indicate that it is safe for topical application on skin. These findings suggested the preventive potential of Clp-EO for the treatment of inflammation linked skin diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Initiation-promotion skin carcinogenesis and immunological competence.

PubMed

Curtis, G L; Stenbäck, F; Ryan, W L

1975-10-01

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

Toxicological evaluation of essential oil from the leaves of Croton tetradenius (Euphorbiaceae) on Aedes aegypti and Mus musculus.

PubMed

Carvalho, Karine da Silva; E Silva, Sandra Lúcia da Cunha; de Souza, Ivone Antonia; Gualberto, Simone Andrade; da Cruz, Rômulo Carlos Dantas; Dos Santos, Frances Regiane; de Carvalho, Mário Geraldo

2016-09-01

For control of Aedes aegypti, the main vector of dengue, botanical insecticides can be a viable alternative. Herein, we evaluated the chemical composition and insecticidal activity of the essential oils of the leaves of Croton tetradenius on Ae. aegypti larvae and adults. We also evaluated the acute toxicity in Mus musculus. The essential oil chemical analysis was performed using chromatography coupled with mass spectrometry and flame ionization detection. Female mice were used for assessing toxicity according to the Organization for Economic Cooperation and Development's Test Guideline 423/2001. Doses administered to mice orally and intraperitoneally were 5, 50, 300, and 2000 mg kg(-1). There was a greater toxic effect on larvae (LC50 = 0.152 mg mL(-1) and LC90 = 0.297 mg mL(-1)) and on adults (LC50 = 1.842 mg mL(-1) and LC90 = 3.156 mg mL(-1)) of Ae. aegypti after 24 h of exposure, when compared to other periods of exposure. Chemical analysis revealed 26 components, with camphor (25.49 %) as the major component. The acute toxicity via the intraperitoneal route identified an LD50 = 200 mg kg(-1) and by the oral route an LD50 = 500 mg kg(-1). Thus, the essential oil of C. tetradenius presents insecticidal potential for Ae. aegypti and has high safety threshold at the concentrations evaluated in this study.

Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

PubMed

Kumar, Anant; Agarwal, Karishma; Singh, Monika; Saxena, Archana; Yadav, Pankaj; Maurya, Anil Kumar; Yadav, Anju; Tandon, Sudeep; Chanda, Debabrata; Bawankule, Dnyaneshwar U

2018-02-10

Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.

Intestinal antispasmodic effects of Helichrysum italicum (Roth) Don ssp. italicum and chemical identification of the active ingredients.

PubMed

Rigano, Daniela; Formisano, Carmen; Senatore, Felice; Piacente, Sonia; Pagano, Ester; Capasso, Raffaele; Borrelli, Francesca; Izzo, Angelo A

2013-12-12

In the Mediterranean Area, the flowers of Helichrysum italicum ssp. italicum are a traditional remedy for the treatment of intestinal complaints and are used as herbal tea for curing digestive, stomachic and intestinal diseases. In order to find scientific evidence for the traditional utilization of this plant, the effect of an ethanolic extract of Helichrysum italicum was investigated by using in vivo and in vitro experimental models. Then, through bioassay-guided fractionation procedures, active component(s) were identified. Contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with acetylcholine and barium chloride; motility in vivo was evaluated by measuring upper gastrointestinal transit, both in control mice and in mice with experimental intestinal inflammation induced by croton oil. Chromatographic separation techniques such as HPLC and silica gel columns have yielded the active principles of Helichrysum italicum. We found that the ethanolic extract of Helichrysum italicum ssp. italicum flowers elicited antispasmodic actions in the isolated mouse ileum and inhibited transit preferentially in the inflamed gut. A bioassay guided fractionation of the extract yielded the known compounds 12-acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2). Present study supported the traditional use of Helichrysum italicum ssp. italicum flowers for intestinal complaints and through bioassay-guided fractionation procedures from the crude extract we showed that 12-acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2) acted in a synergistic way to produce an intestinal antispasmodic effect. © 2013 Elsevier Ireland Ltd. All rights reserved.

Bioactivity-guided fractionation for anti-inflammatory and analgesic properties and constituents of Xanthium strumarium L.

PubMed

Han, T; Li, H-L; Zhang, Q-Y; Han, P; Zheng, H-C; Rahman, K; Qin, L-P

2007-12-01

The aim of this study was to fractionate an extract of Xanthium strumarium L. (EXS) and to investigate the anti-inflammatory and analgesic properties of the extract and its fractions. The ethanol extract of X. strumarium (EXS) was fractionated on the basis of polarity. Among the different fractions, the n-butanol fraction showed the highest anti-inflammatory activity in the croton-oil-induced ear edema test and furthermore reduced the number of writhings induced by acetic acid in mice in a dose-dependent manner. This indicates that the n-butanol fraction of X. strumarium possesses potent analgesic effects which are likely to be mediated by its anti-inflammatory activity. Bioassay-guided fractionation of EXS led to the isolation and identification of ten caffeoylquinic acids and three heterocyclics by HPLC-DAD-MS(n) from the active n-butanol fraction, implying that the active compounds are polar in nature. The isolated caffeoylquinic acids could partially explain the antinociceptive effect of X. strumarium polar extract.

Anti-inflammatory Hydrolyzable Tannins from Myricaria bracteata.

PubMed

Liu, Jia-Bao; Ding, Ya-Si; Zhang, Ying; Chen, Jia-Bao; Cui, Bao-Song; Bai, Jin-Ye; Lin, Ming-Bao; Hou, Qi; Zhang, Pei-Cheng; Li, Shuai

2015-05-22

Twelve hydrolyzable tannins were obtained from the twigs of Myricaria bracteata, including two new hellinoyl-type dimers, bracteatinins D1 (1) and D2 (2); a new hellinoyl-type trimer, bracteatinin T1 (3); two known monomers, nilotinin M4 (4) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-β-d-glucose (5); six known dimers, tamarixinin A (6), nilotinin D8 (7), hirtellins A (10), B (9), and E (8), and isohirtellin C (11); and a known trimer, hirtellin T3 (12). The structures of the tannins were elucidated by spectroscopic data analysis and comparisons to known tannins. All compounds were evaluated as free radical scavengers using 1,1-diphenyl-2-picrylhydrazyl and hydroxy radicals and compared to the activity of BHT and Trolox. Compound 6 showed a significant anti-inflammatory effect on croton oil-induced ear edema in mice (200 mg/kg, inhibition rate 69.8%) and on collagen-induced arthritis in DBA/1 mice (20 mg/kg, inhibition rate 46.0% at day 57).

Sunflower Oil Supplementation Has Proinflammatory Effects and Does Not Reverse Insulin Resistance in Obesity Induced by High-Fat Diet in C57BL/6 Mice

PubMed Central

Masi, Laureane Nunes; Martins, Amanda Roque; Neto, José César Rosa; do Amaral, Cátia Lira; Crisma, Amanda Rabello; Vinolo, Marco Aurélio Ramirez; de Lima Júnior, Edson Alves; Hirabara, Sandro Massao; Curi, Rui

2012-01-01

High consumption of polyunsaturated fatty acids, such as sunflower oil has been associated to beneficial effects in plasma lipid profile, but its role on inflammation and insulin resistance is not fully elucidated yet. We evaluated the effect of sunflower oil supplementation on inflammatory state and insulin resistance condition in HFD-induced obese mice. C57BL/6 male mice (8 weeks) were divided in four groups: (a) control diet (CD), (b) HFD, (c) CD supplemented with n-6 (CD + n-6), and (d) HFD supplemented with n-6 (HFD + n-6). CD + n-6 and HFD + n-6 were supplemented with sunflower oil by oral gavage at 2 g/Kg of body weight, three times per week. CD and HFD were supplemented with water instead at the same dose. HFD induced whole and muscle-specific insulin resistance associated with increased inflammatory markers in insulin-sensitive tissues and macrophage cells. Sunflower oil supplementation was not efficient in preventing or reducing these parameters. In addition, the supplementation increased pro-inflammatory cytokine production by macrophages and tissues. Lipid profile, on the other hand, was improved with the sunflower oil supplementation in animals fed HFD. In conclusion, sunflower oil supplementation improves lipid profile, but it does not prevent or attenuate insulin resistance and inflammation induced by HFD in C57BL/6 mice. PMID:22988427

Improved anti-inflammatory activity of three new terpenoids derived, by systematic chemical modifications, from the abundant triterpenes of the flowery plant Calendula officinalis.

PubMed

Neukirch, Hannes; D'Ambrosio, Michele; Sosa, Silvio; Altinier, Gianmario; Della Loggia, Roberto; Guerriero, Antonio

2005-05-01

Rings A, D and E of faradiol (1), and ring E of both arnidiol (10) and calenduladiol (4) have been subjected to various selective chemical manipulations to modify polarity, water affinity, H-bonding, sterics, and number of aromatic groups of these anti-inflammatory natural compounds. A total of 15 new and four known pentacyclic triterpenoids have been obtained in this way. Some 13 terpenoids were evaluated for their topical anti-inflammatory activities with respect to inhibition of croton oil induced ear oedema in mouse. Three derivatives of 1, the C(16) benzyl ether 15, the C(30) aldehyde 24, and the C(30) primary alcohol 25 showed significantly improved anti-inflammatory potencies, which is relevant for (future) structure-activity-relationship (SAR) studies.

Revealing anti-inflammation mechanism of water-extract and oil of forsythiae fructus on carrageenan-Induced edema rats by serum metabolomics.

PubMed

Yuan, An; Gong, Lihong; Luo, Lin; Dang, Jue; Gong, Xiaohong; Zhao, Mengjie; Li, Yan; Li, Yunxia; Peng, Cheng

2017-11-01

Forsythiae Fructus is an important Chinese medicine which shows a significant effect against inflammation. This study aimed to investigate the preventive anti-inflammation mechanism of Forsythiae Fructus by serum metabolomics strategy and compare the difference of the metabolism pathways between Forsythia extract and Forsythia oil in rat. Four groups (control group, model group, Forsythia extract group and Forsythia oil group) were orally administered 10mL/kg 0.5% Tween 80 solution, 10mL/kg 0.5% Tween 80 solution, 5g/kg Forsythia extract and 0.48mL/kg Forsythia oil respectively. 30min after drug administration, rat acute inflammation was induced by subcutaneous injection of carrageenan in the right paw in model group, Forsythia extract group and Forsythia oil group. After being administered Forsythia extract and Forsythia oil, the percentage of rat paw edema was significantly decreased (P<0.05) compared with model group. Metabolomics based on UPLC-Q-TOF-MS/MS was used to analyze the collected serum sample. Multivariate analysis was established for metabolomics analysis. According to Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) results, four groups were clearly separated. And thirteen alterative biomarkers were identified in the serum, namely PC (19:0/0:0), LysoPC (20:0), LysoPC (20:1), LysoPC (17:0), Sphingosine, Linoleic acid, 3R-hydroxy-butanoic acid (3-HB), 2-hydroxyhexadecanoic acid, Lactic acid, L-Threonine, L-Leucine, Maleic acid, Adipic acid. The change of biomarkers suggested that Forsythia extract affected Linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, Sphingolipid metabolism and Glycerophospholipid metabolism. Forsythia oil affected Sphingolipid metabolism and Glycerophospholipid metabolism. It indicated that Forsythia extract and Forsythia oil both showed significant preventive anti-inflammatory effect through acting on different metabolism pathways. Moreover, efficacy mechanism of Forsythiae Fructus could recover metabolites disturb in the body through affecting particular drug targets associated with the inflammatory pathway. Copyright © 2017. Published by Elsevier Masson SAS.

Emu oil based nano-emulgel for topical delivery of curcumin.

PubMed

Jeengar, Manish Kumar; Rompicharla, Sri Vishnu Kiran; Shrivastava, Shweta; Chella, Naveen; Shastri, Nalini R; Naidu, V G M; Sistla, Ramakrishna

2016-06-15

Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis. Copyright © 2016 Elsevier B.V. All rights reserved.

IMMUNO-DETECTION OF SIGNALING INTERMEDIATES IN AN INTACT LUNG PREPARATION FOLLOWING METALLIC EXPOSURE

EPA Science Inventory

Residual oil fly ash (ROFA) is a particulate pollutant produced during the combustion of fuel oil. ROFA exposure causes adverse respiratory effects in humans and induces lung inflammation in animals and inflammatory mediator expression in cultured human airway epithelial cells....

Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats.

PubMed

Moreira, Eduardo L G; Rial, Daniel; Duarte, Filipe S; de Carvalho, Cristiane Ribeiro; Horst, Heros; Pizzolatti, Moacir G; Prediger, Rui D S; Ribeiro-do-Valle, Rosa Maria

2010-08-01

The aim of the present study was to evaluate the possible neurobehavioural effects in rats of the proanthocyanidin-rich fraction (PRF) isolated from the bark of Croton celtidifolius (Euphorbiaceae). Adult Wistar rats were treated with the PRF (0.3-30 mg/kg) and evaluated in different behavioural paradigms classically used for the screening of drugs with psychoactive effects. Acute intraperitoneal (i.p.) administration of PRF decreased spontaneous locomotor activity (open field arena and activity cage), enhanced the duration of ethyl ether-induced hypnosis, increased the latency to the first convulsion induced by pentylenetetrazole (60 mg/kg, i.p.) and attenuated apomorphine-induced (0.5 mg/kg, i.p.) stereotyped behaviour. In lower doses, PRF (0.3 or 3 mg/kg, i.p.) increased the frequency of open arm entries in the elevated plus-maze test. The present findings suggest that the systemic administration of PRF induces a wide spectrum of behavioural alterations in rats, consistent with the putative existence of hypnosedative, anticonvulsant and anxiolytic compounds.

Impairment of α(2)-macroglobulin synthesis in experimental hepatopathic rats treated with turpentine oil.

PubMed

Kuribayashi, Takashi; Seita, Testuro; Honjo, Toshio; Yamazaki, Shunsuke; Momotani, Eiichi; Yamamoto, Shizuo

2012-01-01

The aim of this study was to investigate the synthesis of α(2)-macroglobulin (α2M) in hepatopathic rats injected with turpentine oil to induce acute inflammation. Hepatopathy was induced by oral administration of acetaminophen at a dose of 1 g/kg daily for 2 weeks or a 25% solution of carbon tetrachloride (CCl(4)) at 2 ml/kg body weight three times per week for 7 weeks. Acute inflammation was induced by intramuscular injection of turpentine oil at a dose of 1.0 ml/kg body weight. Serum concentrations of α2M were measured by enzyme-linked immunosorbent assay. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total protein differed significantly between acetaminophen or CCl(4)-induced hepatopathic rats and acetaminophen control (AA-control) or CCl(4) control (CC-control) rats. Furthermore, pathological examination confirmed hepatopathy in rat livers. Peak serum concentrations and area under the time-concentration curve for α2M showed significant differences between hepatopathic rats and AA-control or CC-control rats. Thus, serum concentrations of α2M did not increase when compared with nontreated rats.

Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability.

PubMed

Boisramé-Helms, Julie; Delabranche, Xavier; Klymchenko, Andrey; Drai, Jocelyne; Blond, Emilie; Zobairi, Fatiha; Mely, Yves; Hasselmann, Michel; Toti, Florence; Meziani, Ferhat

2014-11-01

The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)-induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell-growth medium was supplemented with three different industrial lipid emulsions: Intralipid(®), containing long-chain triglycerides (LCT--soybean oil); Medialipid(®), containing LCT (soybean oil) and medium-chain triglycerides (MCT--coconut oil); and SMOFlipid(®), containing LCT, MCT, omega-9 and -3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid(®) compared to Intralipid(®), SMOFlipid(®) and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid-treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n-3 and n-9 fatty acids have no effect on endotoxin-induced cell death and inflammation.

Turpentine oil induced inflammation decreases absorption and increases distribution of phenacetin without altering its elimination process in rats.

PubMed

Prasad, V G N V; Vivek, Ch; Anand Kumar, P; Ravi Kumar, P; Rao, G S

2015-03-01

Plasma concentrations and pharmacokinetics of phenacetin, a CYP1A2 substrate were determined in normal and experimentally induced inflamed rats by turpentine oil to know the role of inflammation on the pharmacokinetics of phenacetin and formation of its active metabolite (paracetamol) by CYP1A2 in wistar albino rats, weighing about 200-250 g that were randomly divided into two groups consisting six in each group. Rats in group I (control) received phenacetin (150 mg kg(-1), PO) where as group II received phenacetin 12 h after induction of inflammation by turpentine oil (0.4 mL, i.m). Blood samples were collected from retro orbital plexus at pre-determined time intervals prior to and at 0.166, 0.33, 0.67, 1.5, 2, 4, 8 and 12 h post-administration of phenacetin. Plasma was separated and analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on plasma concentrations of phenacetin and its metabolite paracetamol, the pharmacokinetic parameters were determined by compartmental methods. C(max) of phenacetin was significantly (p < 0.01) decreased to 19.50 ± 2.74 μg mL(-1) in inflamed conditions compared to 38.13 ± 2.20 μg mL(-1) obtained in normal rats. Except, for significant (p < 0.001) increase in volume of distribution at steady state (V(dss)) from 2.87 ± 0.37 to 8.03 ± 1.26 L kg(-1) and increased the rate of absorption with shorter absorption half-life (t(1/2ka)) for phenacetin in inflammation. None of the pharmacokinetic parameters of either phenacetin or its metabolite paracetamol were affected. It can be concluded that turpentine oil induced inflammation has no role on the activity of CYP1A2 in rats, as the plasma concentrations and pharmacokinetic parameters of paracetamol were found unaltered.

Houttuynia cordata Thunb. volatile oil exhibited anti-inflammatory effects in vivo and inhibited nitric oxide and tumor necrosis factor-α production in LPS-stimulated mouse peritoneal macrophages in vitro.

PubMed

Li, Weifeng; Fan, Ting; Zhang, Yanmin; Fan, Te; Zhou, Ping; Niu, Xiaofeng; He, Langchong

2013-11-01

Houttuynia cordata Thunb. (HC) is a medicinal herb that generally used in traditional Chinese medicine for treating allergic inflammation. The present study investigated the inhibitory effect of the volatile oil from HC Thunb. on animal models of inflammation and the production of inflammatory mediators in vivo and in vitro. In vivo, xylene-induced mouse ear edema, formaldehyde-induced paw edema and carrageenan-induced mice paw edema were significantly decreased by HC volatile oil. HC volatile oil showed pronounced inhibition of prostaglandin (PG) E2 and malondialdehyde production in the edematous exudates. In vitro exposure of mouse resident peritoneal macrophages to 1, 10, 100 and 1000 µg/mL of HC volatile oil significantly suppressed lipopolysaccharide (LPS)-stimulated production of NO and tumor necrosis factor-α (TNF-α) in a dose-dependent manner. Exposure to HC volatile oil had no effect on cell viability and systemic toxicity. Furthermore, HC volatile oil inhibited the production of NO and TNF-α by down-regulating LPS-stimulated iNOS and TNF-α mRNA expression. Western blot analysis showed that HC volatile oil attenuated LPS-stimulated synthesis of iNOS and TNF-α protein in the macrophages, in parallel. These findings add a novel aspect to the biological profile of HC and clarify its anti-inflammatory mechanism. Copyright © 2012 John Wiley & Sons, Ltd.

Ultraviolet carcinogenesis in the hairless mouse skin. Influence of the sunscreen 2-ethylhexyl-p-methoxycinnamate.

PubMed

Gallagher, C H; Greenoak, G E; Reeve, V E; Canfield, P J; Baker, R S; Bonin, A M

1984-10-01

The mutagenicity of some samples of a commonly used sunscreen, 2-ethylhexyl-p-methoxycinnamate (2-EHMC), led to these studies of its potential carcinogenicity in the HRA/Skh hairless mouse. In a daily treatment regime, repeated for 9 weeks, groups of mice were painted on the dorsum with 2-EHMC, and were then exposed to low doses of one of two artificial ultraviolet (UV) light sources. Mice were also treated with UV alone and with 2-EHMC alone. The accumulated UV exposure alone produced tumours in 40-100% of mice. However, 2-EHMC-treated mice were protected. Subsequent treatment of the 2-EHMC-protected mice, and mice previously treated with 2-EHMC alone, with the tumour promoter, croton oil, produced tumours on a significant number of animals. We conclude that 2-EHMC protects from UV tumorigenesis in the absence of a tumour promoter. However, although tumours appeared on only 4 out of 160 2-EHMC-treated mice exposed to UV, the carcinogenic process had been initiated in others, as application of the tumour promoter, croton oil, produced tumours. Statistical analysis of the incidence of promoted tumours inferred that prior irradiation with UV may not have been implicated. Therefore, 2-EHMC itself may initiate tumours in this strain of hairless mouse.

Docosahexaenoic Acid Attenuates Hepatic Inflammation, Oxidative Stress, and Fibrosis without Decreasing Hepatosteatosis in a Ldlr−/− Mouse Model of Western Diet-Induced Nonalcoholic Steatohepatitis123

PubMed Central

Depner, Christopher M.; Philbrick, Kenneth A.; Jump, Donald B.

2013-01-01

The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with the incidence of obesity. While both NAFLD and NASH are characterized by hepatosteatosis, NASH is characterized by hepatic damage, inflammation, oxidative stress, and fibrosis. We previously reported that feeding Ldlr−/− mice a high-fat, high-cholesterol diet containing menhaden oil attenuated several markers of NASH, including hepatosteatosis, inflammation, and fibrosis. Herein, we test the hypothesis that DHA [22:6 (n-3)] is more effective than EPA [20:5 (n-3)] at preventing Western diet (WD)-induced NASH in Ldlr−/− mice. Mice were fed the WD supplemented with either olive oil (OO), EPA, DHA, or EPA + DHA for 16 wk. WD + OO feeding induced a severe NASH phenotype, characterized by robust hepatosteatosis, inflammation, oxidative stress, and fibrosis. Whereas none of the C20–22 (n-3) fatty acid treatments prevented WD-induced hepatosteatosis, all 3 (n-3) PUFA-containing diets significantly attenuated WD-induced inflammation, fibrosis, and hepatic damage. The capacity of dietary DHA to suppress hepatic markers of inflammation (Clec4F, F4/80, Trl4, Trl9, CD14, Myd88), fibrosis (Procol1α1, Tgfβ1), and oxidative stress (NADPH oxidase subunits Nox2, p22phox, p40phox, p47phox, p67phox) was significantly greater than dietary EPA. The effects of DHA on these markers paralleled DHA-mediated suppression of hepatic Fads1 mRNA abundance and hepatic arachidonic acid content. Because DHA suppression of NASH markers does not require a reduction in hepatosteatosis, dietary DHA may be useful in combating NASH in obese humans. PMID:23303872

South American plants II: taspine isolation and anti-inflammatory activity.

PubMed

Perdue, G P; Blomster, R N; Blake, D A; Farnsworth, N R

1979-01-01

Croton lechleri L. (Euphorbiaceae), a plant from the Upper Amazon Valley of Peru, yielded the alkaloid taspine. The anti-inflammatory activity of taspine hydrochloride was studied using the carrageenan-induced pedal edema method, the cotton pellet-induced granuloma method, and the adjuvant polyarthritis model.

Shrimp oil extracted from the shrimp processing waste reduces the development of insulin resistance and metabolic phenotypes in diet-induced obese rats.

PubMed

Nair, Sandhya; Gagnon, Jacques; Pelletier, Claude; Tchoukanova, Nadia; Zhang, Junzeng; Ewart, H Stephen; Ewart, K Vanya; Jiao, Guangling; Wang, Yanwen

2017-08-01

Diet-induced obesity, insulin resistance, impaired glucose tolerance, chronic inflammation, and oxidative stress represent the main features of type 2 diabetes mellitus. The present study was conducted to examine the efficacy and mechanisms of shrimp oil on glucose homeostasis in obese rats. Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control. Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation. The results demonstrated that shrimp oil dose-dependently improved glycemic control in obese rats through multiple mechanisms.

Anti-inflammatory and antinociceptive activities of Croton urucurana Baillon bark.

PubMed

Cordeiro, Kátia Wolff; Felipe, Josyelen Lousada; Malange, Kauê Franco; do Prado, Pâmela Rafaela; de Oliveira Figueiredo, Patrícia; Garcez, Fernanda Rodrigues; de Cássia Freitas, Karine; Garcez, Walmir Silva; Toffoli-Kadri, Mônica Cristina

2016-05-13

Croton urucurana (Euphorbiaceae) is popularly used in Brazil to treat inflammatory processes, pain, and gastric ulcers. To evaluate the anti-inflammatory and antinociceptive properties of the methanol extract from the bark of C. urucurana (MECu) in mice and identify its chemical constituents. The extract was characterized by UHPLC-DAD-ESI-Q-TOF-MS/MS. Extract doses of 25, 100, and 400mg/kg were employed in the biological assays. Evaluation of anti-inflammatory activity was based on paw edema and leukocyte recruitment into the peritoneal cavity of mice, both induced by carrageenan. Abdominal writhing caused by acetic acid and duration of formalin-induced paw-licking were the models employed to evaluate antinociceptive activity. Ten compounds were identified in the extract: (+)-gallocatechin (1), procyanidin B3 (2), (+)-catechin (3), (-)-epicatechin (4), tembetarine (5), magnoflorine (6), taspine (7), methyl-3-oxo-12-epi-barbascoate (8), methyl-12-epi-barbascoate (9), and hardwickiic acid (10). This is the first report of compounds 2, 4, 6, 7, and 10 in C. urucurana and compound 5 in the genus Croton. In addition to inhibiting paw edema and leukocyte recruitment (particularly of polymorphonuclear cells) into the peritoneal cavity of mice, MECu reduced the number of abdominal writhings induced by acetic acid and the duration of formalin-induced paw licking. The methanol extract of C. urucurana bark exhibited anti-inflammatory and antinociceptive properties, corroborating its use in folk medicine. These effects may be related to the presence of diterpenes, alkaloids, and flavonoids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Induction of steatohepatitis (NASH) with insulin resistance in wildtype B6 mice by a western-type diet containing soybean oil and cholesterol.

PubMed

Henkel, Janin; Coleman, Charles Dominic; Schraplau, Anne; Jӧhrens, Korinna; Weber, Daniela; Castro, José Pedro; Hugo, Martin; Schulz, Tim Julius; Krämer, Stephanie; Schürmann, Annette; Püschel, Gerhard Paul

2017-03-21

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g. high-fat diets) or overweight and insulin resistance (e.g. methionine-choline-deficient diets) or they are based on monogenetic defects (e.g. ob/ob mice). In the current study, a western-type diet containing soybean oil with high n 6-PUFA and 0.75% cholesterol (SOD+Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast a soybean oil-containing western-type diet without cholesterol (SOD) induced only mild steatosis but neither hepatic inflammation nor fibrosis, weight gain or insulin resistance. Another high-fat diet mainly consisting of lard and supplemented with fructose in drinking water (LAD+Fru) resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD+Cho but livers were devoid of inflammation and fibrosis. Although both LAD+Fru- and SOD+Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD+Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. Summarizing, dietary cholesterol in SOD+Cho diet may trigger hepatic inflammation and fibrosis. SOD+Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH.

Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis.

PubMed

Lazic, Milos; Inzaugarat, Maria Eugenia; Povero, Davide; Zhao, Iris C; Chen, Mark; Nalbandian, Madlena; Miller, Yury I; Cherñavsky, Alejandra C; Feldstein, Ariel E; Sears, Dorothy D

2014-01-01

Obesity is associated with metabolic perturbations including liver and adipose tissue inflammation, insulin resistance, and type 2 diabetes. Omega-6 fatty acids (ω6) promote and omega-3 fatty acids (ω3) reduce inflammation as they can be metabolized to pro- and anti-inflammatory eicosanoids, respectively. 12/15-lipoxygenase (12/15-LO) enzymatically produces some of these metabolites and is induced by high fat (HF) diet. We investigated the effects of altering dietary ω6/ω3 ratio and 12/15-LO deficiency on HF diet-induced tissue inflammation and insulin resistance. We examined how these conditions affect circulating concentrations of oxidized metabolites of ω6 arachidonic and linoleic acids and innate and adaptive immune system activity in the liver. For 15 weeks, wild-type (WT) mice were fed either a soybean oil-enriched HF diet with high dietary ω6/ω3 ratio (11∶1, HFH), similar to Western-style diet, or a fat Kcal-matched, fish oil-enriched HF diet with a low dietary ω6/ω3 ratio of 2.7∶1 (HFL). Importantly, the total saturated, monounsaturated and polyunsaturated fat content was matched in the two HF diets, which is unlike most published fish oil studies in mice. Despite modestly increased food intake, WT mice fed HFL were protected from HFH-diet induced steatohepatitis, evidenced by decreased hepatic mRNA expression of pro-inflammatory genes and genes involved in lymphocyte homing, and reduced deposition of hepatic triglyceride. Furthermore, oxidized metabolites of ω6 arachidonic acid were decreased in the plasma of WT HFL compared to WT HFH-fed mice. 12/15-LO knockout (KO) mice were also protected from HFH-induced fatty liver and elevated mRNA markers of inflammation and lymphocyte homing. 12/15-LOKO mice were protected from HFH-induced insulin resistance but reducing dietary ω6/ω3 ratio in WT mice did not ameliorate insulin resistance or adipose tissue inflammation. In conclusion, lowering dietary ω6/ω3 ratio in HF diet significantly reduces steatohepatitis.

Anti-oedematous activities of the main triterpendiol esters of marigold (Calendula officinalis L.).

PubMed

Zitterl-Eglseer, K; Sosa, S; Jurenitsch, J; Schubert-Zsilavecz, M; Della Loggia, R; Tubaro, A; Bertoldi, M; Franz, C

1997-07-01

Separation and isolation of the genuine faradiol esters (1, 2) from flower heads of Marigold (Calendula (officinalis L., Asteraceae) could be achieved by means of repeated column chromatography (CC) and HPLC for the first time. Structure elucidation of faradiol-3-myristic acid ester 1, faradiol-3-palmitic acid ester 2 and psi-taraxasterol 3 has been also performed, without any previous degradation by means of MS, 1H-NMR, 13C-NMR and 2D-NMR experiments. The anti-oedematous activities of these three compounds were tested by means of inhibition of Croton oil-induced oedema of the mouse ear. Both faradiol esters showed nearly the same dose dependent anti-oedematous activity and no significant synergism appeared with their mixture. The free monol, psi-taraxasterol, had a slightly lower effect. Furthermore, faradiol was more active than its esters and than psi-taraxasterol and showed the same effect as an equimolar dose of indomethacin.

Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice.

PubMed

Varghese, C D; Nair, S C; Panikkar, B; Panikkar, K R

1993-04-15

The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (-)-epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil was inhibited by the topical application of 100 mg/kg body weight (b.w.) of (-)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2-4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 microgram/ml of (-)-epicatechin, further highlighting its antiproliferative effect.

Menhaden Oil Decreases High-Fat Diet–Induced Markers of Hepatic Damage, Steatosis, Inflammation, and Fibrosis in Obese Ldlr−/− Mice123

PubMed Central

Depner, Christopher M.; Torres-Gonzalez, Moises; Tripathy, Sasmita; Milne, Ginger; Jump, Donald B.

2012-01-01

The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20–22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20–22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet–induced fatty liver disease in mice. Wild-type (WT) and Ldlr−/− C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF–high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1α1), and oxidative stress (heme oxygenase-1) (P ≤ 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr−/− mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr−/− mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20–22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet–induced markers of fatty liver disease in mice. PMID:22739374

40 CFR 180.341 - 2,4-Dinitro-6-octylphenyl crotonate and 2,6-dinitro-4-octylphenyl crotonate; tolerances for...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false 2,4-Dinitro-6-octylphenyl crotonate and 2,6-dinitro-4-octylphenyl crotonate; tolerances for residues. 180.341 Section 180.341 Protection... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.341 2,4-Dinitro-6-octylphenyl...

The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Zamzami, Mazin A; Alnefayee, Abeer M

2016-11-04

Liver disease is the major cause of serious health problem leading to morbidity and mortality worldwide and the problem has increased in search for hepatotherapeutic agents from plants. The present study was designed to compare the probable hepatoprotective activity of olive oil and N. sativa oil on CCl 4 induced liver damage in male rats. Forty males of a new model of albino rats (Wistar strain) (175-205 g) were divided into four groups. The 1st Group (G1) was the negative control group, the remaining rats were injected with CCl 4 (1 ml/kg body weight) with equal amount of olive oil on the 1st and 4th day of every week for 4 weeks. The 2nd group (G2) was the positive control, the 3rd group (G3) and the fourth group (G4) were treated orally with N. sativa oil and olive oils using stomach tube. The positive control group showed an increase in hepatic enzymes, total bilirubin, creatinine, uric acid, lipid peroxide total cholesterol, triglyceride, low density lipoprotein, very low density lipoproteins, interleukin-6, and a decrease in antioxidant enzymes, high density lipoprotein cholesterol, a decrease in total protein and albumin an when compared with negative control group. Histology of the CCl 4 treated group revealed inflammation and damage of liver cells. Treating the hepatotoxic rats with olive oil and N. sativa oil showed a significant improvement in all biochemical tests compared with the positive CCl 4 control group. In addition, the liver tissues of olive oil treated group showed mild improvement in inflammatory infiltration and in N. sativa oil treated group showed normal hepatocytes with no evidence of inflammation. This study revealed that olive oil and N. sativa oil have a protective effect against CCl 4 -induced hepatotoxicity in male rats. Nigella sativa oil was more effective than olive oil.

Perilla Oil Has Similar Protective Effects of Fish Oil on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Gut Dysbiosis.

PubMed

Tian, Yu; Wang, Hualin; Yuan, Fahu; Li, Na; Huang, Qiang; He, Lei; Wang, Limei; Liu, Zhiguo

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries. Recent studies indicated that the modification of gut microbiota plays an important role in the progression from simple steatosis to steatohepatitis. Epidemiological studies have demonstrated consumption of fish oil or perilla oil rich in n-3 polyunsaturated fatty acids (PUFAs) protects against NAFLD. However, the underlying mechanisms remain unclear. In the present study, we adopted 16s rRNA amplicon sequencing technique to investigate the impacts of fish oil and perilla oil on gut microbiomes modification in rats with high-fat diet- (HFD-) induced NAFLD. Both fish oil and perilla oil ameliorated HFD-induced hepatic steatosis and inflammation. In comparison with the low-fat control diet, HFD feeding significantly reduced the relative abundance of Gram-positive bacteria in the gut, which was slightly reversed by either fish oil or perilla oil. Additionally, fish oil and perilla oil consumption abrogated the elevated abundance of Prevotella and Escherichia in the gut from HFD fed animals. Interestingly, the relative abundance of antiobese Akkermansia was remarkably increased only in animals fed fish oil compared with HFD group. In conclusion, compared with fish oil, perilla oil has similar but slightly weaker potency against HFD-induced NAFLD and gut dysbiosis.

Effects of Testosterone on Erythropoiesis in a Female Mouse Model of Anemia of Inflammation

PubMed Central

Schmidt, Paul J.; Fleming, Mark D.; Bhasin, Shalender

2016-01-01

The anemia of inflammation is a common problem in inflammatory and autoimmune diseases. We characterized a mouse model of anemia of chronic inflammation induced by repeated injections of low doses of heat-killed Brucella abortus (HKBA), and determined the effects of T administration on erythropoiesis in this model. Female C57BL/6NCrl mice were injected weekly with HKBA for 10 wk. Weekly injections of T or vehicle oil were started 4 wk later. Control mice were injected with saline and vehicle oil in parallel. HKBA-injected mice had significantly lower hemoglobin, hematocrit, mean corpuscular volume, reticulocyte hemoglobin, transferrin saturation (TSAT), and tissue nonheme iron in liver and spleen, enlarged spleen, and up-regulated hepatic expression of inflammatory markers, serum amyloid A1, and TNFα, but down-regulated IL-6, bone morphogenic protein 6, and hepcidin compared with saline controls. HKBA also reduced serum hepcidin and increased serum erythropoietin. Bone marrow erythroid precursors were substantially reduced in HKBA-injected mice. Cotreatment with T increased the percentage of late-stage erythroid precursors in the bone marrow relative to HKBA-injected and saline controls and reversed HKBA-induced suppression of hemoglobin and hematocrit. T also normalized serum erythropoietin, TSAT, and reticulocyte hemoglobin without correcting the expression of the hepatic inflammation markers. Conclusions are that low-dose HKBA induces moderate anemia characterized by chronic inflammation, decreased iron stores, and suppression of erythroid precursors in the bone marrow. T administration reverses HKBA-induced anemia by stimulating erythropoiesis, which is associated with a shift toward accelerated maturation of erythroid precursors in the bone marrow. PMID:27074351

Involvement of Inflammation and Adverse Vascular Remodelling in the Blood Pressure Raising Effect of Repeatedly Heated Palm Oil in Rats

PubMed Central

Ng, Chun-Yi; Kamisah, Yusof; Faizah, Othman; Jubri, Zakiah; Qodriyah, Hj Mohd Saad; Jaarin, Kamsiah

2012-01-01

Oil thermoxidation during deep frying generates harmful oxidative free radicals that induce inflammation and increase the risk of hypertension. This study aimed to investigate the effect of repeatedly heated palm oil on blood pressure, aortic morphometry, and vascular cell adhesion molecule-1 (VCAM-1) expression in rats. Male Sprague-Dawley rats were divided into five groups: control, fresh palm oil (FPO), one-time-heated palm oil (1HPO), five-time-heated palm oil (5HPO), or ten-time-heated palm oil (10HPO). Feeding duration was six months. Blood pressure was measured at baseline and monthly using tail-cuff method. After six months, the rats were sacrificed and the aortic arches were dissected for morphometric and immunohistochemical analyses. FPO group showed significantly lower blood pressure than all other groups. Blood pressure was increased significantly in 5HPO and 10HPO groups. The aortae of 5HPO and 10HPO groups showed significantly increased thickness and area of intima-media, circumferential wall tension, and VCAM-1 than other groups. Elastic lamellae were disorganised and fragmented in 5HPO- and 10HPO-treated rats. VCAM-1 expression showed a significant positive correlation with blood pressure. In conclusion, prolonged consumption of repeatedly heated palm oil causes blood pressure elevation, adverse remodelling, and increased VCAM-1, which suggests a possible involvement of inflammation. PMID:22778962

The effects of dietary fish oil on inflammation, fibrosis and oxidative stress associated with obstructive renal injury in rats.

PubMed

Peake, Jonathan M; Gobe, Glenda C; Fassett, Robert G; Coombes, Jeff S

2011-03-01

We examined whether dietary supplementation with fish oil modulates inflammation, fibrosis and oxidative stress following obstructive renal injury. Three groups of Sprague-Dawley rats (n=16 per group) were fed for 4 wk on normal rat chow (oleic acid), chow containing fish oil (33 g eicosapentaenoic acid and 26 g docosahexaenoic acid per kg diet), or chow containing safflower oil (60 g linoleic acid per kg diet). All diets contained 7% fat. After 4 wk, the rats were further subdivided into four smaller groups (n=4 per group). Unilateral ureteral obstruction was induced in three groups (for 4, 7 and 14 days). The fourth group for each diet did not undergo surgery, and was sacrificed as controls at 14 days. When rats were sacrificed, plasma and portions of the kidneys were removed and frozen; other portions of kidney tissue were fixed and prepared for histology. Compared with normal chow and safflower oil, fish oil attenuated collagen deposition, macrophage infiltration, TGF-β expression, apoptosis, and tissue levels of arachidonic acid, MIP-1α, IL-1β, MCP-1 and leukotriene B(4). Compared with normal chow, fish oil increased the expression of HO-1 protein in kidney tissue. Fish oil intake reduced inflammation, fibrosis and oxidative stress following obstructive renal injury. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil.

PubMed

Intahphuak, S; Khonsung, P; Panthong, A

2010-02-01

This study investigated some pharmacological properties of virgin coconut oil (VCO), the natural pure oil from coconut [Cocos nucifera Linn (Palmae)] milk, which was prepared without using chemical or high-heat treatment. The anti-inflammatory, analgesic, and antipyretic effects of VCO were assessed. In acute inflammatory models, VCO showed moderate anti-inflammatory effects on ethyl phenylpropiolate-induced ear edema in rats, and carrageenin- and arachidonic acid-induced paw edema. VCO exhibited an inhibitory effect on chronic inflammation by reducing the transudative weight, granuloma formation, and serum alkaline phosphatase activity. VCO also showed a moderate analgesic effect on the acetic acid-induced writhing response as well as an antipyretic effect in yeast-induced hyperthermia. The results obtained suggest anti-inflammatory, analgesic, and antipyretic properties of VCO.

Anti-inflammatory activity of leaf essential oil from Cinnamomum longepaniculatum (Gamble) N. Chao.

PubMed

Du, Yong-Hua; Feng, Rui-Zhang; Li, Qun; Wei, Qin; Yin, Zhong-Qiong; Zhou, Li-Jun; Tao, Cui; Jia, Ren-Yong

2014-01-01

The anti-inflammatory activity of the essential oil from C. longepaniculatum was evaluated by three experimental models including the dimethyl benzene-induced ear edema in mice, the carrageenan-induced paw edema in rat and the acetic acid-induced vascular permeability in mice. The influence of the essential oil on histological changes and prostaglandin E2 (PGE2), histamine and 5-hydroxytryptamine (5-HT) production associated with carrageenan-induced rat paw edema was also investigated. The essential oil (0.5, 0.25, 0.13 ml/kg b.w.) showed significantly inhibition of inflammation along with a dose-dependent manner in the three experimental models. The anti-inflammatory activity of essential oil was occurred both in early and late phase and peaked at 4 h after carrageenan injection. The essential oil resulted in a dose dependent reduction of the paw thickness, connective tissue injury and the infiltration of inflammatory cell. The essential oil also significantly reduced the production of PGE2, histamine and 5-HT in the exudates of edema paw induced by carrageenan. Both the essential oil and indomethacin resulted relative lower percentage inhibition of histamine and 5-HT than that of PGE2 at 4 h after carrageenan injection.

Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats.

PubMed

Shahzad, Muhammad; Yang, Xudong; Raza Asim, M B; Sun, Qingzhu; Han, Yan; Zhang, Fujun; Cao, Yongxiao; Lu, Shemin

2009-02-01

The black seeds, from the Ranunculaceae family, have been traditionally used by various cultures as a natural remedy for several ailments. In this study, we examined the effect of black seed oil as an immunomodulator in a rat model of allergic airway inflammation. Rats sensitized to ovalbumin and challenged intranasally with ovalbumin to induce an allergic inflammatory response were compared to ovalbumin-sensitized, intranasally ovalbumin-exposed rats pretreated with intraperitoneally administered black seed oil and to control rats. The levels of IgE, IgG1 and ova-specific T-cell proliferation in spleen were measured by ELISA. The pro-inflammatory cytokine IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression levels were measured by reverse transcription polymerase chain reaction. The intraperitoneal administration of black seed oil inhibited the Th2 type immune response in rats by preventing inflammatory cell infiltration and pathological lesions in the lungs. It significantly decreased the nitric oxide production in BALF, total serum IgE, IgG1 and OVA-specific IgG1 along with IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression. Black seed oil treatment resulted in decreased T-cell response evident by lesser delayed type hypersensitivity and lower T-cell proliferation in spleen. In conclusion, black seed oil exhibited a significant reduction in all the markers of allergic inflammation mainly by inhibiting the delayed type hypersensitivity and T-cell proliferation. The data suggests that inhibition of T-cell response may be responsible for immunomodulatory effect of black seed oil in the rat model of allergic airway inflammation.

APOPTOTIC AND INFLAMMATORY EFFECTS INDUCED BY DIFFERENT PARTICLES IN HUMAN ALVEOLAR MACROPHAGES

EPA Science Inventory

Pollutant particles induce apoptosis and inflammation, but the relationship between these two biological processes is not entirely clear. In this study, we compared the proapoptotic and proinflammatory effects of four particles: residual oil fly ash (ROFA), St. Louis particles SR...

18. Photocopied October 1976, from b.f.Tower, Illistrations of the Croton ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. Photocopied October 1976, from b.f.Tower, Illistrations of the Croton Aqueduct, New York, Wiley and Putnam, 1843. ENTRANCE VENTILATOR, PLATE VI, PAGE 88. - Old Croton Aqueduct, New York County, NY

Corn oil enhancing hepatic lipid peroxidation induced by CCl4 does not aggravate liver fibrosis in rats.

PubMed

Fang, Hsun-Lang; Lin, Wen-Chuan

2008-06-01

Lipid peroxidation (LPO) is known to be associated with liver fibrosis in chronic liver injury. However, direct effects of the products of LPO on liver fibrogenesis have not been demonstrated. In this study, we examined the LPO products of carbon tetrachloride (CCl4)+corn oil to evaluate the effect of LPO products on liver fibrosis. CCl4 was given twice a week for 8 weeks. Corn oil was given daily to rats at a dose of 2 or 10ml/kg via gastrogavage throughout the whole experiment period. CCl4 induced both cyclooxygenase (COX)-2 independent and COX-2 dependent LPO. COX-2 independent LPO was enhanced by corn oil treatment while no effect was reflected on COX-2 dependent LPO. CCl4-induced liver fibrosis in rats was not aggravated by corn oil treatment. In addition, the amount of fatty liver induced by CCl4 was increased by corn oil treatment. Though the inflammation-related UCP-2 mRNA expression was induced by CCl4, it was not aggravated by the enhancement of corn oil. corn oil enriches polyunsaturated fatty acids through COX-2 independent pathways to increase LPO products that do not enhance liver fibrosis induced by CCl4.

Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury.

PubMed

Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

2017-01-01

Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Production of 68Ga-citrate Based on a SnO2 Generator for Short-Term Turpentine Oil-Induced Inflammation Imaging in Rats.

PubMed

Mirzaei, Alireza; Jalilian, Amir R; Akhlaghi, Mehdi; Beiki, Davood

2016-01-01

Gallium-68 citrate has been successfully applied in the PET imaging of infections and inflammation in some centers; however further evaluation of the tracer in inflammation models is of great importance. 68Ga-citrate prepared from [68Ga]GaCl3 (eluted form an SnO2 based 68Ge/68Ga generator) and sodium citrate at optimized conditions followed by quality control tests was injected to normal and turpentine-oil induced rats PET/CT imaging studies up to 290 min. 68Ga-citrate was prepared with acceptable radiochemical purity (>99 ITLC, >99% HPLC), specific activity (28-30 GBq/mM), chemical purity (Sn, Fe <0.3 ppm; Zn<0.2 ppm) in 15 min at 50°C. PET/CT imaging of the tracer demonstrated early detection of inflamed site in animal models in 60-80 min. This study demonstrated possible early detection of inflammation foci in vivo using 68Ga-citrate prepared using commercially available 68Ge/68Ga generators for PET imaging. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediated synovial neurogenic plasma extravasation.

PubMed

Pietruck, Christian; Grond, Stefan; Xie, Guo-Xi; Palmer, Pamela P

2003-05-01

Local anesthetics are used for local irrigation after many types of operations. However, recent evidence of toxic effects of local anesthetics at large concentrations during continuous administration suggests an advantage of using decreased local anesthetic concentrations for irrigation solutions. In this study, we determined whether smaller concentrations of local anesthetics may maintain an antiinflammatory and, therefore, analgesic effect without the risk of possible toxicity. Lidocaine and bupivacaine were studied for their ability to inhibit both components of neurogenic inflammation-C fiber-mediated and sympathetic postganglionic neuron (SPGN)-mediated inflammation-in the rat knee joint. Intraarticular lidocaine 0.02% reduced 5-hydroxytryptamine (5-HT)-induced (SPGN-mediated) plasma extravasation (PE) by 35%, and further decreases were obtained by perfusing larger concentrations of lidocaine. Intraarticular bupivacaine 0.025% inhibited 5-HT-induced PE by 60%, and a 95% inhibition was obtained with bupivacaine 0.05%. Larger local anesthetic concentrations were necessary to inhibit C fiber-mediated PE than those required to inhibit SPGN-mediated PE. Lidocaine 0.4% was required to reduce mustard oil-induced PE by 60%. Lidocaine 2% inhibited mustard oil-induced PE to baseline levels. Bupivacaine 0.1% was required for an 80% reduction of PE. Bupivacaine 0.25% inhibited mustard oil-induced PE to baseline levels. Our results demonstrate differential effects of local anesthetics on SPGN- and C fiber-mediated PE but confirm the concept of using smaller concentrations of local anesthetics to achieve inhibition of postoperative inflammation. Local anesthetic wound irrigation is often used to treat postoperative surgical pain. Large concentrations of local anesthetics are usually used, and these concentrations may have possible neurotoxic and myotoxic effects. Our results demonstrate antiinflammatory effects of lidocaine and bupivacaine at concentrations smaller than used clinically.

Perilla Oil Has Similar Protective Effects of Fish Oil on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Gut Dysbiosis

PubMed Central

Tian, Yu; Wang, Hualin; Yuan, Fahu; Li, Na; Huang, Qiang; He, Lei; Wang, Limei

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries. Recent studies indicated that the modification of gut microbiota plays an important role in the progression from simple steatosis to steatohepatitis. Epidemiological studies have demonstrated consumption of fish oil or perilla oil rich in n-3 polyunsaturated fatty acids (PUFAs) protects against NAFLD. However, the underlying mechanisms remain unclear. In the present study, we adopted 16s rRNA amplicon sequencing technique to investigate the impacts of fish oil and perilla oil on gut microbiomes modification in rats with high-fat diet- (HFD-) induced NAFLD. Both fish oil and perilla oil ameliorated HFD-induced hepatic steatosis and inflammation. In comparison with the low-fat control diet, HFD feeding significantly reduced the relative abundance of Gram-positive bacteria in the gut, which was slightly reversed by either fish oil or perilla oil. Additionally, fish oil and perilla oil consumption abrogated the elevated abundance of Prevotella and Escherichia in the gut from HFD fed animals. Interestingly, the relative abundance of antiobese Akkermansia was remarkably increased only in animals fed fish oil compared with HFD group. In conclusion, compared with fish oil, perilla oil has similar but slightly weaker potency against HFD-induced NAFLD and gut dysbiosis. PMID:27051672

47. Photocopied October 1976, from b.f.Tower, Illistrations of the Croton ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

47. Photocopied October 1976, from b.f.Tower, Illistrations of the Croton Aqueduct, New York, Wiley and Putnam, 1843. ISOMETRICAL VIEW OF THE DISTRIBUTING RESERVIOR, PLATE XXIV, PAGE 119. - Old Croton Aqueduct, New York County, NY

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

PubMed

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-06-01

Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings.

An Evaluation of NEPTUNE - A Program for Estimating Life-Cycle Cost of Oily Waste/Waste Oil Collection, Transportation and Treatment Systems.

DTIC Science & Technology

1981-04-01

are listed in Appendix B. There was a significant problem with the formal auditing of the NEPTUNE predictions since a complete manual checking effort...WRSE R. Z. ien BROKLY ! ACcA BSTON SATH CROTON SAT VALJLJO OUZ~A 5.3. NW AD AX A’s AMS AOFT AG! AZ AOSS AD "’s A AS& ASI AT! A’S AVM cc C"~ Cv DC OD963

Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

PubMed

Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-01-14

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

Sesame oil mitigates nutritional steatohepatitis via attenuation of oxidative stress and inflammation: a tale of two-hit hypothesis.

PubMed

Periasamy, Srinivasan; Chien, Se-Ping; Chang, Po-Cheng; Hsu, Dur-Zong; Liu, Ming-Yie

2014-02-01

Nonalcoholic fatty liver disease, the most common chronic liver disorder worldwide, comprises conditions from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular carcinoma. Sesame oil, a healthful food, increases resistance to oxidative stress, inflammation and protects against multiple organ injury in various animal models. We investigated the protective effect of sesame oil against nutritional steatohepatitis in mice. C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 28 days to induce NASH. Sesame oil (1 and 2 ml/kg) was treated from 22nd to 28th day. Body weight, steatosis, triglycerides, aspartate transaminase, alanine transaminase, nitric oxide, malondialdehyde, tumor necrosis factor-α, interlukin-6, interleukin-1β, leptin, and transforming growth factor-β1 (TGF-β1) were assessed after 28 days. All tested parameters were higher in MCD-fed mice than in normal control mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with steatosis, oxidative stress, and necrotic inflammation. In sesame-oil-treated mice, all tested parameters were significantly attenuated compared with MCD-alone mice. Sesame oil inhibited oxidative stress, inflammatory cytokines, leptin, and TGF-β1 in MCD-fed mice. In addition, histological analysis showed that sesame oil provided significant protection against fibrotic collagen. We conclude that sesame oil protects against steatohepatitic fibrosis by decreasing oxidative stress, inflammatory cytokines, leptin and TGF-β1. Copyright © 2014 Elsevier Inc. All rights reserved.

Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice.

PubMed

Jia, Qian; Ivanov, Ivan; Zlatev, Zlatomir Z; Alaniz, Robert C; Weeks, Brad R; Callaway, Evelyn S; Goldsby, Jennifer S; Davidson, Laurie A; Fan, Yang-Yi; Zhou, Lan; Lupton, Joanne R; McMurray, David N; Chapkin, Robert S

2011-08-01

Both fish oil (FO) and curcumin have potential as anti-tumour and anti-inflammatory agents. To further explore their combined effects on dextran sodium sulphate (DSS)-induced colitis, C57BL/6 mice were randomised to four diets (2 × 2 design) differing in fatty acid content with or without curcumin supplementation (FO, FO+2 % curcumin, maize oil (control, MO) or MO+2 % curcumin). Mice were exposed to one or two cycles of DSS in the drinking-water to induce either acute or chronic intestinal inflammation, respectively. FO-fed mice exposed to the single-cycle DSS treatment exhibited the highest mortality (40 %, seventeen of forty-three) compared with MO with the lowest mortality (3 %, one of twenty-nine) (P = 0·0008). Addition of curcumin to MO increased (P = 0·003) mortality to 37 % compared with the control. Consistent with animal survival data, following the one- or two-cycle DSS treatment, both dietary FO and curcumin promoted mucosal injury/ulceration compared with MO. In contrast, compared with other diets, combined FO and curcumin feeding enhanced the resolution of chronic inflammation and suppressed (P < 0·05) a key inflammatory mediator, NF-κB, in the colon mucosa. Mucosal microarray analysis revealed that dietary FO, curcumin and FO plus curcumin combination differentially modulated the expression of genes induced by DSS treatment. These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon.

Near-infrared and ultraviolet induced isomerization of crotonic acid in N{sub 2} and Xe cryomatrices: First observation of two high-energy trans C–O conformers and mechanistic insights

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuş, Nihal; Department of Physics, Anadolu University, 26470 Eskişehir; Fausto, Rui, E-mail: rfausto@ci.uc.pt

2014-12-21

E-crotonic acid was isolated in cryogenic solid N{sub 2} and xenon matrices, and subjected to Laser ultraviolet (UV) and near-infrared (NIR) irradiations. In the deposited matrices, the two low-energy cis C–O E-cc and E-ct conformers, which are the only forms significantly populated in the gas phase, were observed. UV irradiation (λ= 250 nm) of the compound in N{sub 2} matrix allows for experimental detection, not just of the two low-energy cis C–O isomers of Z-crotonic acid previously observed in the experiments carried out in argon matrix [Z-cc and Z-ct; R. Fausto, A. Kulbida, and O. Schrems, J. Chem. Soc., Faradaymore » Trans. 91, 3755–3770 (1995)] but also of the never observed before high-energy forms of both E- and Z-crotonic acids bearing the carboxylic acid group in the trans arrangement (E-tc and Z-tc conformers). In turn, NIR irradiation experiments in the N{sub 2} matrix allow to produce the high-energy E-tc trans C–O conformer in a selective way, from the initially deposited E-cc form. The vibrational signatures of all the 6 rotameric structures of the crotonic acids experimentally observed, including those of the new trans C–O forms, were determined and the individual spectra fully assigned, also with support of theoretically obtained data. On the other hand, as found before for the compound isolated in argon matrix, the experiments performed in xenon matrix failed to experimental detection of the trans C–O forms. This demonstrates that in noble gas matrices these forms are not stable long enough to allow for their observation by steady state spectroscopy techniques. In these matrices, the trans C–O forms convert spontaneously into their cis C–O counterparts, by tunnelling. Some mechanistic details of the studied processes were extracted and discussed.« less

Geraniol attenuates 2-acetylaminofluorene induced oxidative stress, inflammation and apoptosis in the liver of wistar rats.

PubMed

Hasan, Syed Kazim; Sultana, Sarwat

2015-01-01

2-Acetylaminofluorene (2-AAF), is a well-known liver toxicant, generally used to induce tumors in laboratory animals. Geraniol (GE), a monoterpene found in essential oils of herbs and fruits, has been known to possess preventive efficacy against chemically induced toxicities. The present study was designed to analyze the protective effect of GE against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic tissue damage in the liver of female Wistar rats. 2-AAF (0.02% w/w in diet) was administered and subjected to partial hepatectomy, as a mitogenic stimulus for the induction of hyperproliferation of liver tissue. GE was pre-treated orally at two different doses (100 and 200 mg/kg b.wt.) dissolved in corn oil. GE pre-treatment significantly ameliorated 2-AAF induced oxidative damage by diminishing tissue lipid peroxidation accompanied by the increase in enzymatic activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase and reduced glutathione content. The level of serum toxicity markers (AST, ALT, LDH) was found to be decreased. Pre-treatment with GE downregulated the expression of caspase-3,9, COX-2, NFkB, PCNA, iNOS, VEGF and significantly decreased disintegration of DNA. Histological findings further revealed that GE significantly restores the architecture of liver tissue. In the light of the above observations it may be concluded that GE may be used as preventive agent against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic damage.

7. Photocopied December 1977, form F.B. Tower, Illustrations of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Photocopied December 1977, form F.B. Tower, Illustrations of the Croton Aqueduct, New York: Wiley and Putnam, 1843. CROTON AQUEDUCT AT SING SING, PLATE XIII, PAGE 101. - Old Croton Aqueduct, Sing Sing Kill Bridge, Spanning Aqueduct Street & Broadway, Ossining, Westchester County, NY

Anti-inflammatory, antiproliferative and cytoprotective potential of the Attalea phalerata Mart. ex Spreng. pulp oil

PubMed Central

Lescano, Caroline Honaiser; Arrigo, Jucicléia da Silva; Cardoso, Cláudia Andrea Lima; Coutinho, Janclei Pereira; Moslaves, Iluska Senna Bonfá; Ximenes, Thalita Vieira do Nascimento; Kadri, Monica Cristina Toffoli; Weber, Simone Schneider; Perdomo, Renata Trentin; Kassuya, Cândida Aparecida Leite; Vieira, Maria do Carmo; Sanjinez-Argandoña, Eliana Janet

2018-01-01

The anti-inflammatory, antiproliferative and cytoprotective activity of the Attalea phalerata Mart. ex Spreng pulp oil was evaluated by in vitro and in vivo methods. As for the chemical profile, the antioxidant activity was performed by spectrophotometry, and the profile of carotenoids and amino acids by chromatography. Our data demonstrated that A. phalerata oil has high carotenoid content, antioxidant activity and the presence of 5 essential amino acids. In the in vitro models of inflammation, the oil demonstrated the capacity to inhibit COX1 and COX2 enzymes, the production of nitric oxide and also induces macrophages to spreading. In the in vivo models of inflammation, the oil inhibited edema and leukocyte migration in the Wistar rats. In the in vitro model of antiproliferative and cytoprotective activity, the oil was shown inactive against the kidney carcinoma and prostate carcinoma lineage cells and with cytoprotective capacity in murine fibroblast cells, inhibiting the cytotoxic action of doxorubicin. Therefore, it is concluded that A. phalerata pulp oil has anti-inflammatory effects with nutraceutical properties potential due to the rich composition. Moreover, the oil also has cytoprotective activity probably because of its ability to inhibit the action of free radicals. PMID:29634766

Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri.

PubMed

Risco, Ester; Ghia, Felipe; Vila, Roser; Iglesias, José; Alvarez, Elida; Cañigueral, Salvador

2003-09-01

The immunomodulatory activity of the latex from Croton lechleri (sangre de drago) was determined by in vitro assays. Classical (CP) and alternative (AP) complement pathways activities were determined in human serum. Intracellular generation of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and monocytes, and phagocytosis of opsonised fluorescent microspheres were measured by flow cytometry. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes was also investigated. In addition, anti-inflammatory activity was assayed in vivo by carrageenan-induced rat paw oedema test. Some of the activities were compared with those of the isolated alkaloid taspine. Sangre de drago from Croton lechleri showed immunomodulatory activity. It exhibited a potent inhibitory activity on CP and AP of complement system and inhibited the proliferation of activated T-cells. The latex showed free radical scavenging capacity. Depending on the concentration, it showed antioxidant or prooxidant properties, and stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti-inflammatory activity when administered i. p. Taspine cannot be considered the main responsible for these activities, and other constituents, probably proanthocyanidins, should be also involved.

Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

PubMed

Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

2012-06-01

The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer.

Olive oil-induced reduction of oxidative damage and inflammation promotes wound healing of pressure ulcers in mice.

PubMed

Donato-Trancoso, Aline; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

2016-07-01

The overproduction of reactive oxygen species (ROS) and exacerbated inflammatory response are the main events that impair healing of pressure ulcers. Therefore, olive oil may be a good alternative to improve the healing of these chronic lesions due to its anti-inflammatory and antioxidant properties. This study investigated the effect of olive oil administration on wound healing of pressure ulcers in mice. Male Swiss mice were daily treated with olive oil or water until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induced pressure ulcer formation. The olive oil administration accelerated ROS and nitric oxide (NO) synthesis and reduced oxidative damage in proteins and lipids when compared to water group. The inflammatory cell infiltration, gene tumor necrosis factor-α (TNF-α) expression and protein neutrophil elastase expression were reduced by olive oil administration when compared to water group. The re-epithelialization and blood vessel number were higher in the olive oil group than in the water group. The olive oil administration accelerated protein expression of TNF-α, active transforming growth factor-β1 and vascular endothelial growth factor-A when compared to water group. The collagen deposition, myofibroblastic differentiation and wound contraction were accelerated by olive oil administration when compared to water group. Olive oil administration improves cutaneous wound healing of pressure ulcers in mice through the acceleration of the ROS and NO synthesis, which reduces oxidative damage and inflammation and promotes dermal reconstruction and wound closure. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Isolation of a dihydrobenzofuran lignan from South American dragon's blood (Croton spp.) as an inhibitor of cell proliferation.

PubMed

Pieters, L; de Bruyne, T; Claeys, M; Vlietinck, A; Calomme, M; vanden Berghe, D

1993-06-01

Dragon's blood is a red viscous latex extracted from the cortex of various Croton spp. (Euphorbiaceae), most commonly Croton lechleri, Croton draconoides (or Croton palanostigma), and Croton erythrochilus. It is used in South American popular medicine for several purposes, including wound healing. Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3',4-O-dimethylcedrusin or 4-O-methyldihydrodehydrodiconiferyl alcohol [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-methoxybenzo furan-5- propan-1-ol] [1] as the biologically active principle. A related compound, 4-O-methylcedrusin [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzo furan-5- propan-1-ol] [2], and the alkaloid taspine [3], also isolated from dragon's blood, were not active in the same assay. A cell proliferation assay, measuring the incorporation of tritiated thymidine in endothelial cells, showed that compound 1 did not stimulate cell proliferation, but rather inhibited thymidine incorporation, while protecting cells against degradation in a starvation medium.

Anti-oxidative, anti-inflammatory and hepato-protective effects of Ligustrum robustum.

PubMed

Lau, Kit-Man; He, Zhen-Dan; Dong, Hui; Fung, Kwok-Pui; But, Paul Pui-Hay

2002-11-01

Aqueous extract of processed leaves of Ligustrum robustum could dose-dependently scavenge superoxide radicals, inhibit lipid peroxidation, and prevent AAPH-induced hemolysis of red blood cells. In comparison with green tea, oolong tea and black tea, processed leaves of L. robustum exhibited comparable antioxidant potency in scavenging superoxide radicals and in preventing red blood cell hemolysis. By activity-guided fractionation, a glycoside-rich fraction named fraction B2 was separated and demonstrated to possess strong antioxidant effect. It was evaluated for its anti-inflammatory and hepato-protective activities. A single oral dose of fraction B2 at 0.5 g/kg could provide 51.5% inhibition on the vascular permeability change induced by intraperitoneal injection of acetic acid, but it could not inhibit croton oil-induced ear edema. On the other hand, fraction B2 exhibited moderate hepato-protective effect. Intragastric application of fraction B2 at 1.25, 2.5 or 5 g/kg 6 h after carbon tetrachloride administration could reduce the elevations of serum levels of aminotransferases (AST and ALT). Also, liver integrity was preserved, as liver sections from rats post-treated with fraction B2 showed a milder degree of fatty accumulation and necrosis. These results offer partial support to the traditional uses of the leaves of L. robustum as Ku-Ding-Cha.

Biochemical characterization, anti-inflammatory properties and ulcerogenic traits of some cold-pressed oils in experimental animals.

PubMed

Ibrahim, Faten M; Attia, Hanan Naeim; Maklad, Yousreya Aly Aly; Ahmed, Kawkab A; Ramadan, Mohamed F

2017-12-01

Cold-pressed oils (CPO) are commercially available in the market and characterized by their health-promoting properties. Clove oil (CLO), coriander seed oil (COO) and black cumin oil (BCO) were evaluated for their bioactive lipids. Pharmacological screening was performed to evaluate acute toxicity, anti-inflammatory and ulcerogenic effects as well as histopathological changes in tissues of albino rats fed with CPO. Fatty acids, tocols and total phenolics were analyzed. The acute toxicity test for each CPO was estimated during 14 d. Carrageenan-induced rat paw oedema was used for assessment of anti-inflammatory activity of CPO. Animals were fasted overnight, and via oral gavage given indomethacin (10 mg/kg) or CPO (400 mg/kg) to investigate ulcerogenecity. Histopathological changes in liver, kidney, heart, spleen and stomach were screened. Amounts of α-, β-, γ- and δ-tocopherols in CLO were 1495, 58, 4177 and 177 mg/kg oil, respectively. In COO, α, β, γ and δ-tocopherols were 10.0, 18.2, 5.1 and 34.8%, respectively. In BCO, β-tocotrienol was the main constituent. CLO, COO and BCO contained 4.6, 4.2 and 3.6 mg GAE/g, respectively. Acute toxicity test determined that 400 mg/kg of CPO to be used. In the carrageenan model of inflammation, pretreatment of rats with indomethacin (10 mg/kg) or CLO (400 mg/kg) induced a significant (p < 0.05) reduction by 31.3 and 27.4%, respectively, in rat paw oedema as compared with the carrageenan-treated group. Indomethacin induced a significant ulcerogenic effect with an ulcer index of 19. Oral treatment of CPO showed no ulcerogenic effect, wherein no histopathological changes were observed. CPO, particularly CLO, could minimize acute inflammation.

Extraction Optimization of Tinospora cordifolia and Assessment of the Anticancer Activity of Its Alkaloid Palmatine

PubMed Central

Ali, Huma; Dixit, Savita

2013-01-01

Objective. To optimize the conditions for the extraction of alkaloid palmatine from Tinospora cordifolia by using response surface methodology (RSM) and study its anticancerous property against 7,12-dimethylbenz(a)anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. Methods. The effect of three independent variables, namely, extraction temperature, time, and cycles was investigated by using central composite design. A single topical application of DMBA (100 μg/100 μL of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) for 16 weeks, exhibited 100 percent tumor incidence (Group 2). Results. The highest yield of alkaloid from Tinospora cordifolia could be achieved at 16 hours of extraction time under 40°C with 4 extraction cycles. Alkaloid administration significantly decreases tumor size, number, and the activity of serum enzyme when compared with the control (Group 2). In addition, depleted levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase and increased DNA damage were restored in palmatine treated groups. Conclusion. The data of the present study clearly indicate the anticancer potential of palmatine alkaloid in DMBA induced skin cancer model in mice. PMID:24379740

Protective Effect of Camellia Oil (Camellia oleifera Abel.) against Ethanol-Induced Acute Oxidative Injury of the Gastric Mucosa in Mice.

PubMed

Tu, Pang-Shuo; Tung, Yu-Tang; Lee, Wei-Ting; Yen, Gow-Chin

2017-06-21

Camellia oil, a common edible oil in Taiwan and China, has health effects for the gastrointestinal tract in folk medicine, and it contains abundant unsaturated fatty acids and phytochemicals. However, the preventive effect of camellia oil on ethanol-induced gastric ulcers remains unclear. This study was aimed to evaluate the preventive effect of camellia oil on ethanol-induced gastric injury in vitro and in vivo as well as its mechanisms of action. In an in vitro study, our results showed that pretreatment of RGM-1 cells with camellia oil enhanced the migration ability as well as increased heat shock protein expression and reduced apoptotic protein expression. In animal experiments, mice pretreated with camellia oil effectively showed improved ethanol-induced acute injury of the gastric muscosa and oxidative damage through the enhancement of antioxidant enzyme activities and heat shock protein and PGE 2 production, as well as the suppression of lipid peroxidation, apoptosis-related proteins, pro-inflammatory cytokines, and NO production. Histological injury score and hemorrhage score in ethanol-induced gastric mucosal damage dramatically elevated from the control group (0.00 ± 0.0) to 3.40 ± 0.7 and 2.60 ± 0.5, respectively. However, treatments with camellia oil or olive oil (2 mL/kg bw) and lansoprazole (30 mg/kg bw) showed significant decreases in elevation of injury score and hemorrhage score (p < 0.05). Therefore, camellia oil has the potential to ameliorate ethanol-induced acute gastric mucosal injury through the inhibition of inflammation and oxidative stress.

Vitex negundo inhibits cyclooxygenase-2 inflammatory cytokine-mediated inflammation on carrageenan-induced rat hind paw edema

PubMed Central

Chattopadhyay, Pronobesh; Hazarika, Soilyadhar; Dhiman, Sunil; Upadhyay, Aadesh; Pandey, Anurag; Karmakar, Sanjeev; Singh, Lokendra

2012-01-01

Background: Vitex negundo L. (Verbenaceae) is a hardy plant widely distributed in the Indian subcontinent and used for treatment of a wide spectrum of health disorders in traditional and folk medicine, some of which have been experimentally validated. In present study, we aimed to investigate the anti-inflammatory effects of V. negundo in carrageenan-induced paw edema in rats, and to investigate the probable mechanism of anti-inflammatory action. Materials and Methods: Paw edema was produced by injecting 1% solution of carrageenan, and the paw volume was measured before and after carrageenan injection up to 5 h. V. negundo leaf oil was extracted using a Clevenger apparatus and administered by a trans-dermal route to Wistar rats and the percentage of inhibition of inflammation was observed using a Plethysmometer by comparing a compound aerosol-based formulation with 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP/kg body weight served as a standard drug whereas paraffin oil served as the placebo group. After withdrawing of blood, serum was separated and cyclooxygenase (COX)-1 and COX-2 inhibitory activities were measured by the enzyme immuno assay (EIA) method by using a COX inhibitor screening assay kit. Results and Discussion: V. negundo leaf oil significantly (P < 0.05) reduced the carrageenan-induced paw edema as compared to the placebo group (paraffin oil) and 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP showed the maximum inhibition of paw edema as compared to the V. negundo leaf oil treated group and the control group. Also in the present study V. negundo leaf oil showed significantly (P < 0.05) inhibits COX-1 pathways rather than COX-2 pathways as compared to the V. negundo leaf oil treated group. Conclusion: It is suggested that the V. negundo leaf oil is a potent anti-inflammatory agent and acts via inhibition of COX-2 without much interfering COX-1 pathways. PMID:22923950

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat

PubMed Central

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-01-01

Background & objectives: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation & conclusions: High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings. PMID:26205026

Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

PubMed

Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

2016-02-01

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties. © The Author(s) 2015.

Effects of coconut oil on glycemia, inflammation, and urogenital microbial parameters in female Ossabaw mini-pigs.

PubMed

Newell-Fugate, Annie E; Lenz, Katherine; Skenandore, Cassandra; Nowak, Romana A; White, Bryan A; Braundmeier-Fleming, Andrea

2017-01-01

Forty percent of American women are obese and at risk for type II diabetes, impaired immune function, and altered microbiome diversity, thus impacting overall health. We investigated whether obesity induced by an excess calorie, high fat diet containing hydrogenated fats, fructose, and coconut oil (HFD) altered glucose homeostasis, peripheral immunity, and urogenital microbial dynamics. We hypothesized that HFD would cause hyperglycemia, increase peripheral inflammation, and alter urogenital microbiota to favor bacterial taxonomy associated with inflammation. We utilized female Ossabaw mini-pigs to model a 'thrifty' metabolic phenotype associated with increased white adipose tissue mass. Pigs were fed HFD (~4570 kcal/pig/day) or lean (~2000 kcal/pig/day) diet for a total of 9 estrous cycles (~6 months). To determine the effect of cycle stage on cytokines and the microbiome, animals had samples collected during cycles 7 and 9 on certain days of the cycle: D1, 4, 8, 12, 16, 18. Vaginal swabs or cervical flushes assessed urogenital microbiota. Systemic fatty acids, insulin, glucose, and cytokines were analyzed. Pig weights and morphometric measurements were taken weekly. Obese pigs had increased body weight, length, heart and belly girth but similar glucose concentrations. Obese pigs had decreased cytokine levels (IL-1β, TNF-α, IL-4, IL-10), arachidonic acid and plasma insulin, but increased levels of vaccenic acid. Obese pigs had greater urogenital bacterial diversity, including several taxa known for anti-inflammatory properties. Overall, induction of obesity did not induce inflammation but shifted the microbial communities within the urogenital tract to an anti-inflammatory phenotype. We postulate that the coconut oil in the HFD oil may have supported normal glucose homeostasis and modulated the immune response, possibly through regulation of microbial community dynamics and fatty acid metabolism. This animal model holds promise for the study of how different types of obesity and high fat diets may affect metabolism, immune phenotype, and microbial dynamics.

Effects of coconut oil on glycemia, inflammation, and urogenital microbial parameters in female Ossabaw mini-pigs

PubMed Central

Skenandore, Cassandra; Nowak, Romana A.; White, Bryan A.; Braundmeier-Fleming, Andrea

2017-01-01

Forty percent of American women are obese and at risk for type II diabetes, impaired immune function, and altered microbiome diversity, thus impacting overall health. We investigated whether obesity induced by an excess calorie, high fat diet containing hydrogenated fats, fructose, and coconut oil (HFD) altered glucose homeostasis, peripheral immunity, and urogenital microbial dynamics. We hypothesized that HFD would cause hyperglycemia, increase peripheral inflammation, and alter urogenital microbiota to favor bacterial taxonomy associated with inflammation. We utilized female Ossabaw mini-pigs to model a ‘thrifty’ metabolic phenotype associated with increased white adipose tissue mass. Pigs were fed HFD (~4570 kcal/pig/day) or lean (~2000 kcal/pig/day) diet for a total of 9 estrous cycles (~6 months). To determine the effect of cycle stage on cytokines and the microbiome, animals had samples collected during cycles 7 and 9 on certain days of the cycle: D1, 4, 8, 12, 16, 18. Vaginal swabs or cervical flushes assessed urogenital microbiota. Systemic fatty acids, insulin, glucose, and cytokines were analyzed. Pig weights and morphometric measurements were taken weekly. Obese pigs had increased body weight, length, heart and belly girth but similar glucose concentrations. Obese pigs had decreased cytokine levels (IL-1β, TNF-α, IL-4, IL-10), arachidonic acid and plasma insulin, but increased levels of vaccenic acid. Obese pigs had greater urogenital bacterial diversity, including several taxa known for anti-inflammatory properties. Overall, induction of obesity did not induce inflammation but shifted the microbial communities within the urogenital tract to an anti-inflammatory phenotype. We postulate that the coconut oil in the HFD oil may have supported normal glucose homeostasis and modulated the immune response, possibly through regulation of microbial community dynamics and fatty acid metabolism. This animal model holds promise for the study of how different types of obesity and high fat diets may affect metabolism, immune phenotype, and microbial dynamics. PMID:28704429

Muscadine grape seed oil as a novel source of tocotrienols to reduce adipogenesis and adipocyte inflammation.

PubMed

Zhao, Lu; Yagiz, Yavuz; Xu, Changmou; Lu, Jiang; Chung, Soonkyu; Marshall, Maurice R

2015-07-01

Tocotrienols are unsaturated forms of vitamin E previously shown to reduce adipogenesis and adipose inflammation. In this study, muscadine grape seed oil (MGSO) was identified as a novel source of tocotrienols containing significant amounts of α- and γ-tocotrienol (T3) with minor seasonal changes. The aim of this study was to assess the anti-adipogenic and anti-inflammatory potential of MGSO by using primary human adipose-derived stem cells (hASCs). Differentiating hASCs were treated with MGSO and compared with rice bran and olive oil. Accumulation of triglyceride was significantly lower in MGSO-treated hASCs than rice bran and olive oils. A tocotrienol rich fraction (TRF) from MGSO was prepared by solid phase extraction and eluted with 15% 1,4-dioxane in hexane. The MGSO-derived TRF treatment significantly reduced mRNA and protein expression that are crucial to adipogenesis (e.g., PPARγ and aP2) in hASCs. Furthermore, TRF from MGSO markedly reduced LPS-induced proinflammatory gene expression in human adipocytes and cytokine secretion to the medium (IL-6 and IL-8). Collectively, our work suggests that MGSO is a stable and reliable natural source of T3 and MGSO may constitute a new dietary strategy to attenuate obesity and its associated adipose inflammation.

Hepatic protection and anticancer activity of curcuma: a potential chemopreventive strategy against hepatocellular carcinoma.

PubMed

Li, Yan; Shi, Xue; Zhang, Jingwen; Zhang, Xiang; Martin, Robert C G

2014-02-01

Malignant transformation of hepatocellular carcinoma (HCC) occurs through repetitive liver injury in a context of inflammation and oxidative DNA damage. A spectrum of natural sesquiterpenoids from curcuma oil has displayed antioxidant, anti-inflammatory and anti-carcinogenic properties. The aim of the study was to investigate the hepatoprotective and anti-HCC effects of curcuma oil in vivo and in vitro. Mice were pretreated with curcuma oil (100 mg/kg) for 3 days, then treated with Concanavalin A (30 mg/kg). The hepatic tissue was evaluated for histology, CD4+ cell, interferon-γ, apoptosis, lipid peroxidation, 8-hydroxy-deoxyguanosine and MnSOD. C57L/J mice were treated with curcuma oil and 107 Hepa1-6 cells directly inoculated into liver lobes. The effects of curcuma oil on cell growth and cell death were evaluated. In addition, MnSOD, HSP60, catalase, NF-κB and caspase-3 were also investigated in the Hepa1-6 cells treated with curcuma oil. Pretreatment with curcuma oil significantly attenuates inflammation and oxidative damage by Concanavalin A. Treatment with curcuma oil can decrease the incidence of HCC. Curcuma oil inhibits cell growth and induces cell death in Hepa1-6 cells. Curcuma protected mice with hepatic injury from inflammatory and oxidative stress. Curcuma oil can inhibit hepatoma cell growth in vivo and in vitro.

Hepatic protection and anticancer activity of curcuma: A potential chemopreventive strategy against hepatocellular carcinoma

PubMed Central

LI, YAN; SHI, XUE; ZHANG, JINGWEN; ZHANG, XIANG; MARTIN, ROBERT C.G.

2014-01-01

Malignant transformation of hepatocellular carcinoma (HCC) occurs through repetitive liver injury in a context of inflammation and oxidative DNA damage. A spectrum of natural sesquiterpenoids from curcuma oil has displayed anti-oxidant, anti-inflammatory and anti-carcinogenic properties. The aim of the study was to investigate the hepatoprotective and anti-HCC effects of curcuma oil in vivo and in vitro. Mice were pretreated with curcuma oil (100 mg/kg) for 3 days, then treated with Concanavalin A (30 mg/kg). The hepatic tissue was evaluated for histology, CD4+ cell, interferon-γ, apoptosis, lipid peroxidation, 8-hydroxy-deoxyguanosine and MnSOD. C57L/J mice were treated with curcuma oil and 107 Hepa1-6 cells directly inoculated into liver lobes. The effects of curcuma oil on cell growth and cell death were evaluated. In addition, MnSOD, HSP60, catalase, NF-κB and caspase-3 were also investigated in the Hepa1-6 cells treated with curcuma oil. Pretreatment with curcuma oil significantly attenuates inflammation and oxidative damage by Concanavalin A. Treatment with curcuma oil can decrease the incidence of HCC. Curcuma oil inhibits cell growth and induces cell death in Hepa1-6 cells. Curcuma protected mice with hepatic injury from inflammatory and oxidative stress. Curcuma oil can inhibit hepatoma cell growth in vivo and in vitro. PMID:24270742

Pine Oil Effects on Chemical and Thermal Injury in Mice and Cultured Mouse Dorsal Root Ganglion Neurons

PubMed Central

Clark, SP; Bollag, WB; Westlund, KN; Ma, F; Falls, G; Xie, D; Johnson, M; Isales, CM; Bhattacharyya, MH

2013-01-01

A commercial resin-based pine oil derived from Pinus palustris and Pinus elliottii was the major focus of this investigation. Extracts of pine resins, needles and bark are folk medicines commonly used to treat skin ailments, including burns. The American Burn Association estimates that 500,000 people with burn injuries receive medical treatment each year; one-half of US burn victims are children, most with scald burns. This systematic study was initiated as follow-up to personal anecdotal evidence acquired over more than 10 years by MH Bhattacharyya regarding pine oil’s efficacy for treating burns. The results demonstrate that pine oil counteracted dermal inflammation in both a mouse ear model of contact irritant-induced dermal inflammation and a 2nd degree scald burn to the mouse paw. Furthermore, pine oil significantly counteracted the tactile allodynia and soft tissue injury caused by the scald burn. In mouse dorsal root ganglion (DRG) neuronal cultures, pine oil added to the medium blocked ATP-activated, but not capsaicin-activated, pain pathways, demonstrating specificity. These results together support the hypothesis that a pine-oil-based treatment can be developed to provide effective in-home care for 2nd degree burns. PMID:23595692

Inhibitory effects of citronellol and geraniol on nitric oxide and prostaglandin E₂production in macrophages.

PubMed

Su, Yu-Wen; Chao, Shiou-Huei; Lee, Meng-Hwan; Ou, Tsang-Yow; Tsai, Ying-Chieh

2010-10-01

Geranium oil has been used traditionally for diarrhea, dermatitis, and intestinal inflammation in East Asia. The aim of this study was to determine the effects of geranium oil's characteristic components, citronellol and geraniol, on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Citronellol and geraniol suppressed NO and PGE(2) production in a dose-dependent manner. The inhibitory efficacy of geraniol was concomitant with decreases in protein and mRNA expression levels of inducible nitric oxide synthase (iNOS), whereas citronellol inhibited only iNOS enzymatic activity. By adding citronellol and geraniol, the LPS-induced cyclooxygenase-2 (COX-2) protein and mRNA expression levels were significantly attenuated, whereas cytosolic degradation of I κB α and upregulation of NF-κB p65 in the nucleus were reversed. These results suggested that citronellol and geraniol exhibit anti-inflammatory activities, supporting their common use and demonstrating their therapeutic potential for inflammation-associated disorders. © Georg Thieme Verlag KG Stuttgart · New York.

Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis

PubMed Central

Brown, Kirsty; Rajendiran, Ethendhar; Estaki, Mehrbod; Dai, Chuanbin; Yip, Ashley; Gibson, Deanna L.

2013-01-01

Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, ω-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival. PMID:23405155

Fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs LPS dephosphorylation activity causing sepsis.

PubMed

Ghosh, Sanjoy; DeCoffe, Daniella; Brown, Kirsty; Rajendiran, Ethendhar; Estaki, Mehrbod; Dai, Chuanbin; Yip, Ashley; Gibson, Deanna L

2013-01-01

Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, ω-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival.

Amelioration of FCA induced arthritis on topical application of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Mouli Veeravalli, S Chandra; Naidu, V G M; Sistla, Ramakrishna

2016-09-01

The aim of the present study was to investigate the skin penetration potential of emu oil and the possibility of enhancing the antiarthritic potential of lipophilic bioactive curcumin, which has poor permeability through biological membranes. Solubility and ex vivo skin permeation studies were performed with water, corn oil, and emu oil as a vehicle using curcumin as a model drug. Carrageenan induced inflammation and Freund's complete adjuvant-induced arthritic rat models were used to evaluate enhanced antiinflammatory and antiarthritic effect of curcumin in combination of emu oil via topical route. The skin permeation study resulted in the combination of emu oil with curcumin enhancing the flux 1.84 and 4.25 times through the rat skin compared to corn oil and water, respectively. Results of carrageenan induced rat paw edema model demonstrated that percentage of paw inhibition shown by curcumin-emu oil combination was 1.42-fold more compared to the total effect shown by both groups treated with curcumin aqueous suspension and emu oil per se. In Freund's complete adjuvant-induced arthritic model, the combined treatment was effective in bringing significant changes in the functional, biochemical, histopathologic, and radiologic parameters. Topical application of curcumin-emu oil combination resulted in significant reduced levels of proinflammatory mediators TNF-α, IL-1 β, and IL-6 (P < 0.05, 0.001, and 0.01, respectively) compared to arthritic animals. Topical delivery of curcumin with emu oil holds promise as a noninvasive and efficacious intervention for the treatment of inflammatory arthritis and it assists in further development of a topical formulation of curcumin using emu oil as a vehicle. Copyright © 2016 Elsevier Inc. All rights reserved.

Beneficial Effects of Silymarin After the Discontinuation of CCl4-Induced Liver Fibrosis.

PubMed

Clichici, Simona; Olteanu, Diana; Filip, Adriana; Nagy, Andras-Laszlo; Oros, Adrian; Mircea, Petru A

2016-08-01

Silymarin (Si) is a herbal product with hepatoprotective potential, well-known for its antioxidant, anti-inflammatory, and immunomodulatory properties. We have recently demonstrated that the usual therapeutic doses of Si are capable of inhibiting the progression of incipient liver fibrosis. We aimed at further investigating the benefits of Si administration upon liver alterations after the hepatotoxin discontinuation, using CCl4 to induce liver injuries on rats. CCl4 administration induces first of all oxidative stress, but other mechanisms, such as inflammation and liver fibrosis are also triggered. Fifty Wistar rats were randomly divided into five groups (n = 10). The control group received sunflower oil twice a week for 8 weeks. Carboxymethyl cellulose group received sunflower oil twice a week, for 8 weeks and CMC daily, for the next 2 weeks. CCl4 group received CCl4 in sunflower oil, by gavage, twice a week, for 8 weeks. CCl4 + Si 50 group received CCl4 twice a week, for 8 weeks, and then 50 mg/body weight (b.w.) Silymarin for the next 2 weeks. CCl4 + Si 200 group was similar to the previous group, but with Si 200 mg/b.w. Ten weeks after the experiment had begun, we assessed inflammation (IL-6, MAPK, NF-κB, pNF-κB), fibrosis (hyaluronic acid), TGF-β1, MMP-9, markers of hepatic stellate cell activation (α-SMA expression), and proliferative capacity (proliferating cell nuclear antigen). Our data showed that Silymarin administered after the toxic liver injury is capable of reducing inflammation and liver fibrosis. The benefits were more important for the higher dose than for the usual therapeutic dose.

Turpentine-induced inflammation reduces the hepatic expression of the multiple drug resistance gene, the plasma cholesterol concentration and the development of atherosclerosis in apolipoprotein E deficient mice.

PubMed

Tous, Mònica; Ribas, Vicent; Ferré, Natàlia; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco; Alonso-Villaverde, Carlos; Coll, Blai; Camps, Jordi; Joven, Jorge

2005-04-15

We aimed to investigate the effect of turpentine-induced inflammation in an atherosclerosis-prone murine model. We have induced a chronic aseptic inflammation in apolipoprotein E-deficient mice, with or without a dietary supplement of aspirin (n = 10, each), by the injection of a mixture (1:1) of turpentine and olive oil in the hind limb twice weekly for a period of 12 weeks. Control animals were injected with olive oil alone (n = 10). The control mice did show any alteration neither in plasma nor at the site of injection. Turpentine-treated mice showed a significant increase in plasma TNF-alpha and SAA concentrations which indicated a systemic inflammatory response that was not substantially affected by aspirin. Also, turpentine injections significantly reduced the plasma cholesterol concentration, probably decreasing intestinal cholesterol re-absorption, and attenuated the size of atherosclerotic lesion. Both effects were minimally influenced by aspirin. The burden of atherosclerosis correlated with plasma lipid levels but not with plasma inflammatory markers. Finally, there was a concomitant decrease in the expression of the hepatic mdr1b gene that correlated with the decrease in plasma cholesterol concentration. Therefore, we conclude that mdr1 is an additional factor to consider in the complexity of alterations in cholesterol metabolism that occur in this model.

Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice.

PubMed

Lam, Yan Y; Ha, Connie W Y; Hoffmann, Jenny M A; Oscarsson, Jan; Dinudom, Anuwat; Mather, Thomas J; Cook, David I; Hunt, Nicholas H; Caterson, Ian D; Holmes, Andrew J; Storlien, Len H

2015-07-01

To distinguish the effects of dietary fat profile on gut parameters and their relationships with metabolic changes and to determine the capacity of n-3 fatty acids to modify gut variables in the context of diet-induced metabolic dysfunctions. Mice received control or high-fat diets emphasizing saturated (HFD-sat), n-6 (HFD-n6), or n-3 (HFD-n3) fatty acids for 8 weeks. In another cohort, mice that were maintained on HFD-sat received n-3-rich fish oil or resolvin D1 supplementation. HFD-sat and HFD-n6 induced similar weight gain, but only HFD-sat increased index of insulin resistance (HOMA-IR), colonic permeability, and mesenteric fat inflammation. Hydrogen sulfide-producing bacteria were one of the major groups driving the diet-specific changes in gut microbiome, with the overall microbial profile being associated with changes in body weight, HOMA-IR, and gut permeability. In mice maintained on HFD-sat, fish oil and resolvin D1 restored barrier function and reduced inflammation in the colon but were unable to normalize HOMA-IR. Different dietary fat profiles led to distinct intestinal and metabolic outcomes that are independent of obesity. Interventions targeting inflammation successfully restored gut health but did not reverse systemic aspects of diet-induced metabolic dysfunction, implicating separation between gut dysfunctions and disease-initiating and/or -maintaining processes. © 2015 The Obesity Society.

Hydrogeology of the Croton-Ossining area, Westchester County, New York

USGS Publications Warehouse

Reynolds, Richard J.

1988-01-01

The hydrogeology of a 29-sq-mi area surrounding the village of Croton-on-Hudson, New York, is summarized on 6 sheets at 1:12 ,000 scale that show locations of wells and test holes, surficial geology, geologic sections, bedrock geology, land use, and soil permeability. The primary stratified-drift aquifer in this area is the Croton River aquifer, which consists of outwash sand and gravel that partly fills the Croton River valley from the New Croton Dam to the Hudson River--a distance of approximately 3 miles. The valley is narrow and ranges in width from 100 to 1,900 ft, and its v-notch bedrock floor ranges from 30 to 50 ft below sea level. Detailed hydrogeologic studies during 1936-38 showed the stratigraphy to consist of an upper water-table aquifer with a saturated thickness of about 35 ft, underlain by a silt and clay confining unit 8 to o0 ft in thickness that in turn is underlain by a lower confined outwash aquifer up to 40 ft thick. Aquifer-test data and laboratory permeability tests show that the average hydraulic conductivity of the upper outwash aquifer is 475 ft/d, and that of the lower confined aquifer is about 300 ft/d. The aquifer is recharged through direct precipitation, runoff from adjacent hillsides, and leakage under the new Croton Dam. Previous studies estimate the average leakage under the dam to be 0.65 Mgal/d and the total average daily recharge to the aquifer between New Croton Dam and Quaker Bridge to be 1.73 Mgal/d. (USGS)

Effects of subclinical inflammation on C-reactive protein and haptoglobin levels as well as specific humoral immunity in dogs vaccinated against canine distemper and parvovirus.

PubMed

Romiszewski, Przemysław; Kostro, Krzysztof; Lisiecka, Urszula

2018-03-05

The aim of the present study was to assess the effects of subclinical inflammation on specific humoral immunity in dogs vaccinated with Nobivac® DHP based on serum levels of CRP and Hp. Dogs from the group I were administered Nobivac® DHP, the vaccine against distemper, infectious hepatitis and parvovirus whereas group II animals received subcutaneous turpentine oil to induce subclinical inflammation, followed by Nobivac® DHP after 24 h. Animals in group III received only turpentine oil in the way and amount identical to that as in group II. Nobivac DHP relatively poorly induced the immune inflammatory response showing good immunogenic properties, which was evidenced by only a double increase in mean CRP and Hp levels associated with antigenic stimulation in group I. In group II, serum neutralization (SN) and haemagglutination inhibition (HI) results were quite closely correlated with serum levels of CPR and Hp. Our findings suggest that the efficacy of vaccinations in dogs can be significantly affected by subclinical inflammations, which is indicated by a correlation between serum CRP and Hp levels versus antibody titres for canine distemper and parvovirus in both experimental groups of dogs (group I and II). The correlation of mean CRP and Hp values in dogs with subclinical inflammation and after vaccination with the kinetics of increasing antibody titres against distemper and parvovirus in group II dogs reflects the severity of inflammatory response and the extent of specific humoral immunity. Routine determinations of serum CRP and Hp levels as the indices of inflammation severity can be the essential biochemical markers for assessment of dogs' health in the period preceding specific immunoprophylaxis and efficacy of the vaccine.

The Antioxidant Content and Protective Effect of Argan Oil and Syzygium aromaticum Essential Oil in Hydrogen Peroxide-Induced Biochemical and Histological Changes.

PubMed

Bakour, Meryem; Soulo, Najoua; Hammas, Nawal; Fatemi, Hinde El; Aboulghazi, Abderrazak; Taroq, Amal; Abdellaoui, Abdelfattah; Al-Waili, Noori; Lyoussi, Badiaa

2018-02-18

Oxidative stress is an important etiology of chronic diseases and many studies have shown that natural products might alleviate oxidative stress-induced pathogenesis. The study aims to evaluate the effect of Argan oil and Syzygium aromaticum essential oil on hydrogen peroxide (H₂O₂)-induced liver, brain and kidney tissue toxicity as well as biochemical changes in wistar rats. The antioxidant content of Argan oil and Syzygium aromaticum essential oil was studied with the use of gas chromatography. The animals received daily by gavage, for 21 days, either distilled water, Syzygium aromaticum essential oil, Argan oil, H₂O₂ alone, H₂O₂ and Syzygium aromaticum essential oil, or H₂O₂ and Argan oil. Blood samples were withdrawn on day 21 for the biochemical blood tests, and the kidney, liver and brain tissue samples were prepared for histopathology examination. The results showed that the content of antioxidant compounds in Syzygium aromaticum essential oil is higher than that found in Argan oil. H₂O₂ increased level of blood urea, liver enzymes, total cholesterol, Low Density Lipoprotein (LDL-C), Triglycerides (TG) and Very Low Density Lipoprotein (VLDL), and decreased the total protein, albumin and High Density Lipoprotein-cholesterol (HDL-C). There was no significant effect on blood electrolyte or serum creatinine. The histopathology examination demonstrated that H₂O₂ induces dilatation in the central vein, inflammation and binucleation in the liver, congestion and hemorrhage in the brain, and congestion in the kidney. The H₂O₂-induced histopathological and biochemical changes have been significantly alleviated by Syzygium aromaticum essential oil or Argan oil. It is concluded that the Argan oil and especially the mixture of Argan oil with Syzygium aromaticum essential oil can reduce the oxidative damage caused by H₂O 2, and this will pave the way to investigate the protective effects of these natural substances in the diseases attributed to the high oxidative stress.

"Ray-intrusive" laticifers in species of Croton section Cyclostigma (Euphorbiaceae)

Treesearch

Alex C. Wiedenhoeft; Ricarda Riina; Paul E. Berry

2009-01-01

A description of the occurrence and structure of “ray-intrusive” laticifers in the rays of species of Croton section Cyclostigma is provided. The systematic significance of laticifers within Croton section Cyclostigma is briefly discussed in relation to the section’s known production of red latex, commonly called “dragon’s blood”. A developmental hypothesis is offered...

Sectional rearrangement of arborescent clades of Croton (Euphorbiaceae) in South America : evolution of arillate seeds and a new species, Croton domatifer

Treesearch

Ricarda Riina; Benjamin van Ee; Alex C. Wiedenhoeft; Alfonso Cardozo; Paul E. Berry

2010-01-01

Most of the arborescent Croton species in the New World were treated by Webster as belonging either to C. sect. Cyclostigma Griseb. or C. sect. Luntia (Neck. ex Raf.) G.L. Webster. The circumscription of C. sect. Cyclostigma has been treated recently. In this paper we focus on C. sect. Luntia, which was subdivided by Webster into two subsections, C. subsect....

A Nomenclator of Croton (Euphorbiaceae) in Madagascar, the Comoros Archipelago, and the Mascarene Islands

PubMed Central

Berry, Paul E.; Kainulainen, Kent; van Ee, Benjamin W.

2017-01-01

Abstract All published names of Croton from Madagascar, the Comoros, and the Mascarenes are treated here. We indicate which names are currently accepted (123 native species and 1 introduced), which ones we consider to be heterotypic synonyms (188), which ones are doubtful (25), and which ones should be excluded (5). We newly designate lectotypes for 108 names, and epitypes for C. anisatus Baill., C. nobilis Baill., and C. submetallicus Baill. A total of 133 names are newly treated as synonyms. One new combination is made, Croton basaltorum (Leandri) P.E.Berry for C. antanosiensis var. basaltorum Leandri, and one new name is proposed, Croton toliarensis B.W.vanEe & Kainul. for C. tranomarensis var. rosmarinifolius Radcl.-Sm. PMID:29391851

Anti-inflammatory activity and chemical composition of the essential oils from Senecio flammeus

PubMed Central

Xiao, Kai-Jun; Wang, Wen-Xia; Dai, Jia-Li; Zhu, Liang

2014-01-01

Many species from Senecio genus have been used in traditional medicine, and their pharmacological activities have been demonstrated. This study investigated the chemical composition and anti-inflammatory activities of essential oils from Senecio flammeus. A total of 48 components representing 98.41 % of the total oils were identified. The main compounds in the oils were α-farnesene (11.26 %), caryophyllene (8.69 %), n-hexadecanoic acid (7.23 %), and α-pinene (6.36 %). The anti-inflammatory activity of the essential oils was evaluated in rodents (10–90 mg/kg bw) in classical models of inflammation [carrageenan-induced paw edema, 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema, and cotton pellet-induced granuloma]. The essential oils at doses of 10, 30, and 90 mg/kg bw significantly reduced carrageenan-induced paw edema by 17.42 % (P < 0.05), 52.90 % (P < 0.05), and 66.45 % (P < 0.05) 4 h after carrageenan injection, respectively, and significantly reduced myeloperoxidase activity (P < 0.05). The essential oils (10, 30, and 90 mg/kg) also produced a significant dose-dependent response to reduce TPA-induced ear edema by 20.27 % (P < 0.05), 33.06 % (P < 0.05), and 53.90 % (P < 0.05), respectively. The essential oils produced significant dose-response anti-inflammatory activity against cotton pellet-induced granuloma that peaked at the highest dose of 90 mg/kg (49.08 % wet weight and 47.29 % dry weight). Results demonstrate that the essential oils of S. flammeus were effective in the treatment of both acute and chronic inflammatory conditions, thereby supporting the traditional use of this herb. PMID:26417301

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

PubMed

Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

2017-11-01

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

PubMed

Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

2016-04-01

The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Fluorine bearing sydnones with styryl ketone group: synthesis and their possible analgesic and anti-inflammatory activities.

PubMed

Deshpande, Shreenivas Ramachandrarao; Pai, Karkala Vasantakumar

2012-04-01

In continuation of structure activity relationship studies, a panel of fluorine containing sydnones with styryl ketone group 4-[1-oxo-3-(substituted aryl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)sydnones 2a-i, was synthesized as better analgesic and anti-inflammatory agents. The title compounds were formed by condensing 4-acetyl-3-(3-chloro-4-fluorophenyl)sydnone with various substituted aryl aldehydes, characterized by spectral studies and evaluated at 100 mg\\kg b.w., p.o. for analgesic, anti-inflammatory and ulcerogenic activities. Compounds 2c and 2e showed good analgesic effect in acetic acid-induced writhing while none showed significant activity in hot plate assay in mice. In carrageenan-induced rat paw oedema test, compound 2c and 2f exhibited good anti-inflammatory effect at 3rd h, whereas compounds 2c, 2e, 2d, 2g and 2h showed activity in croton oil induced ear oedema assay in mice. Compounds 2c and 2e were less ulcerogenic than ibuprofen in rats, when tested by ulcer index method. Compounds with electron attracting substituents such as 2c and 2e were found to be promising in terms of the ratio of efficacy and adverse effect. These compounds generally exhibited better activity than those of earlier series signifying fluorine substitution.

Severe Intestinal Inflammation in the Small Intestine of Mice Induced by Controllable Deletion of Claudin-7.

PubMed

Li, Wen-Jing; Xu, Chang; Wang, Kun; Li, Teng-Yan; Wang, Xiao-Nan; Yang, Hui; Xing, Tiaosi; Li, Wen-Xia; Chen, Yan-Hua; Gao, Hong; Ding, Lei

2018-05-01

As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development. To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen. We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis. After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened. We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.

Gas chromatographic mass analysis and further pharmacological actions of Cymbopogon proximus essential oil.

PubMed

Al-Taweel, A M; Fawzy, G A; Perveen, S; El Tahir, K E H

2013-09-01

The present study reports Gas chromatographic mass analysis (GC-MS) as well as important biological activities of Cymbopogon proximus essential oil. The chemical composition of the essential oil of Cymbopogon proximus was investigated by GC-MS. Furthermore, the effects of Cymbopogon proximus essential oil on the cardiac parasympathetic ganglia in rats, the intra-tracheal pressure in guinea-pigs and on carrageenan-induced inflammation in the rats paw, were studied. The GC-MS study led to the identification of 22 components with Piperitone representing (73.81%), Elemol (9.32%), alpha-Eudesmol (5.21%) and alpha-Terpineol (3.01%) of the oils composition. The percentage protective effect of the oil on the vagus-induced bradycardia in rats was 90.1±3.1%, which represents a significant protection. As for the effect of Cymbopogon oil on bronchoconstrictors-induced increase in intra-tracheal pressure in guinea-pigs, the oil antagonized the actions of 5-HT and histamine by 80±3.7 and 93±8.3%, respectively. Pharmacological investigations using Cymbopogon oil revealed its inherent ability to possess a bronchodilator activity mediated via blockade of both histamine and serotonin receptors. It possessed a significant ganglionic blocking action and a limited anti-inflammatory activity that seemed to involve blockade of histamine and serotonin receptors in the rats' paws. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on several parameters of Epstein-Barr virus infection.

PubMed

Zhang, Z X; Liu, Y X; Chen, H C; Allaudeen, H S; De Clercq, E

1984-01-01

The selective and potent anti-herpesvirus drug, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU), has been examined for its inhibitory effects on several parameters of Epstein-Barr virus (EBV) infection in the lymphoblastoid cell lines Raji, P3HR-1, B-95-8 and P3 hybrid cells (a human embryo oropharyngeal cell line fused with a nasopharyngeal carcinoma cell line). At a dosage of 0.03 to 0.1 mM, BVdU caused a marked inhibition of (i) spontaneous viral capsid antigen (VCA) expression in B-95-8 and P3 hybrid cells, (ii) VCA expression and DNA synthesis in B-95-8 cells induced with croton oil and n-butyrate, (iii) early antigen (EA) expression and DNA synthesis in Raji cells superinfected with EBV, and (iv) VCA expression and DNA synthesis in B-95-8 cells superinfected with EBV. In its inhibitory effects on these various parameters of EBV infection, BVdU appears to be comparable to acyclovir [9-(2-hydroxyethoxymethyl)guanine], another selective anti-herpesvirus drug which has been previously recognized as an effective inhibitor of EBV replication.

Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts.

PubMed

Han, Xuesheng; Parker, Tory L

2017-12-01

Clove (Eugenia caryophyllata Thunb. [Myrtaceae]) essential oil (CEO) has been shown to possess antimicrobial, antifungal, antiviral, antioxidant, anti-inflammatory and anticancer properties. However, few studies have focused on its topical use. We investigated the biological activity of a commercially available CEO in a human skin disease model. We evaluated the effect of CEO on 17 protein biomarkers that play critical roles in inflammation and tissue remodelling in a validated human dermal fibroblast system, which was designed to model chronic inflammation and fibrosis. Four concentrations of CEO (0.011, 0.0037, 0.0012, and 0.00041%, v/v) were studied. The effect of 0.011% CEO on genome-wide gene expression was also evaluated. CEO at a concentration of 0.011% showed robust antiproliferative effects on human dermal fibroblasts. It significantly inhibited the increased production of several proinflammatory biomarkers such as vascular cell adhesion molecule-1 (VCAM-1), interferon γ-induced protein 10 (IP-10), interferon-inducible T-cell α chemoattractant (I-TAC), and monokine induced by γ interferon (MIG). CEO also significantly inhibited tissue remodelling protein molecules, namely, collagen-I, collagen-III, macrophage colony-stimulating factor (M-CSF), and tissue inhibitor of metalloproteinase 2 (TIMP-2). Furthermore, it significantly modulated global gene expression and altered signalling pathways critical for inflammation, tissue remodelling, and cancer signalling processes. CEO significantly inhibited VCAM-1 and collagen III at both protein and gene expression levels. This study provides important evidence of CEO-induced anti-inflammatory and tissue remodelling activity in human dermal fibroblasts. This study also supports the anticancer properties of CEO and its major active component eugenol.

Dietary fatty acids and inflammation in the vertebral column of Atlantic salmon, Salmo salar L., smolts: a possible link to spinal deformities.

PubMed

Gil Martens, L; Lock, E J; Fjelldal, P G; Wargelius, A; Araujo, P; Torstensen, B E; Witten, P E; Hansen, T; Waagbø, R; Ørnsrud, R

2010-12-01

Vegetable oils (Vo) are an alternative to fish oil (Fo) in aquaculture feeds. This study aimed to evaluate the effect of dietary soybean oil (Vo diet), rich in linoleic acid, and of dietary fish oil (Fo diet) on the development of spinal deformities under bacterial lipopolysaccharide (LPS)-induced chronic inflammation conditions in Atlantic salmon, Salmo salar L. Fish [25 g body weight (BW)] were fed the experimental diets for 99 days. On day 47 of feeding (40 g BW), fish were subjected to four experimental regimes: (i) intramuscular injections with LPS, (ii) sham-injected phosphate-buffered saline (PBS), (iii) intraperitoneally injected commercial oil adjuvant vaccine, or (iv) no treatment. The fish continued under a common feeding regime in sea water for 165 more days. Body weight was temporarily higher in the Vo group than in the Fo group prior to immunization and was also affected by the type of immunization. At the end of the trial, no differences were seen between the dietary groups. The overall prevalence of spinal deformities was approximately 14% at the end of the experiment. The Vo diet affected vertebral shape but did not induce spinal deformities. In groups injected with LPS and PBS, spinal deformities ranged between 21% and 38%, diet independent. Deformed vertebrae were located at or in proximity to the injection point. Assessment of inflammatory markers revealed high levels of plasma prostaglandin E₂ (PGE₂) in the Vo-fed and LPS-injected groups, suggesting an inflammatory response to LPS. Cyclooxigenase 2 (COX-2) mRNA expression in bone was higher in fish fed Fo compared to Vo-fed fish. Gene expression of immunoglobulin M (IgM) was up-regulated in bone of all LPS-injected groups irrespective of dietary oil. In conclusion, the study suggests that Vo is not a risk factor for the development of inflammation-related spinal deformities. At the same time, we found evidence that localized injection-related processes could trigger the development of vertebral body malformations. © 2010 Blackwell Publishing Ltd.

Environmental Impact Research Program. Doveweeds (Croton supp.) Section 7.4.2, US Army Corps of Engineers Wildlife Resources Management Manual.

DTIC Science & Technology

1986-07-01

inflorescences are formed. The inflorescence is an abbre-9viated terminal raceme with pistillate flowers below staminate flowers. The 3 -IC Figure 1...Distribution and distinguishing characteristics of woolly croton (Croton capitatus): (a) flowering branch, (b) fruit, and (c) seeds 4 ovary is 3- celled ...and the capsule is 3- celled and 3-seeded except for C. monanthogynus, which is 1-seeded. When seeds mature in late fall, they are forcefully ejected

The effect of flavonol glycosides on opiate withdrawal.

PubMed

Capasso, Anna

2007-07-01

Our interest has been centered on flavonol glycosides from Croton Menthodorus (Euphorbiaceae) and Aristeguietia discolor (Asteraceae). In this respect, the effect of flavonol glycosides from Croton Menthodorus (Euphorbiaceae) and Aristeguietia discolor (Asteraceae) was investigated on the naloxone-precipitated withdrawal contracture of the acute morphine-dependent guinea-pig ileum in vitro. Furthermore, the effect of these flavonol glycosides was also considered on DAGO (highly selective micro-agonist) and U50-488H (highly selective k-agonist) withdrawal to test whether the possible interaction of flavonol glycosides on opioid withdrawal involves micro- and/or k-opioid receptors. Flavonol glycosides from Croton Menthodorus (1 x 10(-5), 5 x 10(-5) and 1 x 10(-4) M) and from Aristeguietia discolor (1 x 10(-7)-1 x 10(-6)-1 x 10(-5) M) before or after the opioid agonists were able to both prevent and reverse the naloxone-induced contracture after exposure to micro (morphine and DAGO) or k (U50-488H) opiate agonists in a concentration-dependent fashion. Both acetylcholine response and electrical stimulation were reduced by flavonol glycosides treatment as well as the final opiate withdrawal was still reduced. The results of the present study indicate that flavonol glycosides were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at micro and k opioid agonists.

Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and cytokine profiles.

PubMed

Arancioglu, Seren; Ulker, Ozge Cemiloglu; Karakaya, Asuman

2015-01-01

Dermal exposure to chemicals may result in allergic or irritant contact dermatitis. In this study, we performed ex vivo local lymph node assay: bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare the differences between irritation and sensitization potency of some chemicals in terms of the 3 end points: lymphocyte proliferation, cytokine profiles (interleukin 2 [IL-2], interferon-γ (IFN-γ), IL-4, IL-5, IL-1, and tumor necrosis factor α [TNF-α]), and ear swelling. Different concentrations of the following well-known sensitizers and irritant chemicals were applied to mice: dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and croton oil. According to the lymph node results; the auricular lymph node weights and lymph node cell counts increased after application of both sensitizers and irritants in high concentrations. On the other hand, according to lymph node cell proliferation results, there was a 3-fold increase in proliferation of lymph node cells (stimulation index) for sensitizer chemicals and SLS in the applied concentrations; however, there was not a 3-fold increase for croton oil and negative control. The SLS gave a false-positive response. Cytokine analysis demonstrated that 4 cytokines including IL-2, IFN-γ, IL-4, and IL-5 were released in lymph node cell cultures, with a clear dose trend for sensitizers whereas only TNF-α was released in response to irritants. Taken together, our results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for discriminating irritants and allergens. © The Author(s) 2015.

Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine.

PubMed

Ueda, Toshihide; Hokari, Ryota; Higashiyama, Masaaki; Yasutake, Yuichi; Maruta, Koji; Kurihara, Chie; Tomita, Kengo; Komoto, Shunsuke; Okada, Yoshikiyo; Watanabe, Chikako; Usui, Shingo; Nagao, Shigeaki; Miura, Soichiro

2015-01-07

To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine

PubMed Central

Ueda, Toshihide; Hokari, Ryota; Higashiyama, Masaaki; Yasutake, Yuichi; Maruta, Koji; Kurihara, Chie; Tomita, Kengo; Komoto, Shunsuke; Okada, Yoshikiyo; Watanabe, Chikako; Usui, Shingo; Nagao, Shigeaki; Miura, Soichiro

2015-01-01

AIM: To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. METHODS: C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. RESULTS: In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked. PMID:25574090

Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

PubMed Central

da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

2016-01-01

Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiang, Y.-H.; Jen, L.-N.; Su, H.-Y.

Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg body weight diallyl disulfide or diallyl trisulfide, or the vehicle (corn oil; 2 ml/kg body weight) every other day for 2 weeks before being injected with endotoxin (i.p., 5 mg/kg body weight). Control rats were administered with corn oil and were injected with sterile saline. Samples for the measurement of proinflammatory cytokines weremore » collected 3 h after injection, and all other samples were collected 18 h after injection. The low dose of GO suppressed endotoxin-induced inducible nitric oxide synthase (iNOS) activity, ulceration, and apoptosis in the intestinal mucosa (P < 0.05). The high dose of GO significantly lowered the peripheral level of nitrate/nitrite and endotoxin-induced iNOS activity in the intestinal mucosa (P < 0.05) but worsened intestinal mucosal damage accompanied by elevated peripheral proinflammatory cytokines. Diallyl trisulfide but not diallyl disulfide showed similar toxic effect as that of high-dose GO. These results suggest the preventive effect and possible toxicity of garlic oil and its organosulfur compounds in endotoxin-induced systemic inflammation and intestinal damage.« less

Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters.

PubMed

Fayad, Walid; Fryknäs, Mårten; Brnjic, Slavica; Olofsson, Maria Hägg; Larsson, Rolf; Linder, Stig

2009-10-02

Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology. A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak and Bax, mitochondrial cytochrome c release and mitochondrial membrane permeabilization in HCT116 cells. Analysis of the gene expression signature of thaspine-treated cells suggested that thaspine is a topoisomerase inhibitor. Inhibition of both topoisomerase I and II was observed using in vitro assays, and thaspine was found to have a reduced cytotoxic effect on a cell line with a mutated topoisomerase II enzyme. Interestingly, in contrast to the topoisomerase II inhibitors doxorubicin, etoposide and mitoxantrone, thaspine was cytotoxic to cell lines overexpressing the PgP or MRP drug efflux transporters. We finally show that thaspine induces wide-spread apoptosis in colon carcinoma multicellular spheroids and that apoptosis is induced in two xenograft mouse models in vivo. The alkaloid thaspine from the cortex of Croton lechleri is a dual topoisomerase inhibitor effective in cells overexpressing drug efflux transporters and induces wide-spread apoptosis in multicellular spheroids.

Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation.

PubMed

Chen, Fan; Chen, Dandan; Zhao, Xinmei; Yang, Shuai; Li, Zhe; Sanchis, Daniel; Jin, Liang; Qiang, Xizhe; Wang, Kaiye; Xu, Yitao; Zhang, Yubin; Ye, Junmei

2017-12-01

Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

The Antioxidant Content and Protective Effect of Argan Oil and Syzygium aromaticum Essential Oil in Hydrogen Peroxide-Induced Biochemical and Histological Changes

PubMed Central

BAKOUR, Meryem; SOULO, Najoua; HAMMAS, Nawal; FATEMI, Hinde EL; ABOULGHAZI, Abderrazak; TAROQ, Amal; ABDELLAOUI, Abdelfattah; AL-WAILI, Noori; LYOUSSI, Badiaa

2018-01-01

Oxidative stress is an important etiology of chronic diseases and many studies have shown that natural products might alleviate oxidative stress-induced pathogenesis. The study aims to evaluate the effect of Argan oil and Syzygium aromaticum essential oil on hydrogen peroxide (H2O2)-induced liver, brain and kidney tissue toxicity as well as biochemical changes in wistar rats. The antioxidant content of Argan oil and Syzygium aromaticum essential oil was studied with the use of gas chromatography. The animals received daily by gavage, for 21 days, either distilled water, Syzygium aromaticum essential oil, Argan oil, H2O2 alone, H2O2 and Syzygium aromaticum essential oil, or H2O2 and Argan oil. Blood samples were withdrawn on day 21 for the biochemical blood tests, and the kidney, liver and brain tissue samples were prepared for histopathology examination. The results showed that the content of antioxidant compounds in Syzygium aromaticum essential oil is higher than that found in Argan oil. H2O2 increased level of blood urea, liver enzymes, total cholesterol, Low Density Lipoprotein (LDL-C), Triglycerides (TG) and Very Low Density Lipoprotein (VLDL), and decreased the total protein, albumin and High Density Lipoprotein-cholesterol (HDL-C). There was no significant effect on blood electrolyte or serum creatinine. The histopathology examination demonstrated that H2O2 induces dilatation in the central vein, inflammation and binucleation in the liver, congestion and hemorrhage in the brain, and congestion in the kidney. The H2O2-induced histopathological and biochemical changes have been significantly alleviated by Syzygium aromaticum essential oil or Argan oil. It is concluded that the Argan oil and especially the mixture of Argan oil with Syzygium aromaticum essential oil can reduce the oxidative damage caused by H2O2, and this will pave the way to investigate the protective effects of these natural substances in the diseases attributed to the high oxidative stress. PMID:29463041

Inflammation in Response to n3 Fatty Acids in a Porcine Obesity Model

PubMed Central

Faris, Richard J; Boddicker, Rebecca L; Walker-Daniels, Jennifer; Li, Jenny; Jones, Douglas E; Spurlock, Michael E

2012-01-01

Fatty acids have distinct cellular effects related to inflammation and insulin sensitivity. Dietary saturated fat activates toll-like receptor 4, which in turn can lead to chronic inflammation, insulin resistance, and adipose tissue macrophage infiltration. Conversely, n3 fatty acids are generally antiinflammatory and promote insulin sensitivity, in part via peroxisome proliferator-activated receptor γ. Ossabaw swine are a useful biomedical model of obesity. We fed Ossabaw pigs either a low-fat control diet or a diet containing high-fat palm oil with or without additional n3 fatty acids for 30 wk to investigate the effect of saturated fats and n3 fatty acids on obesity-linked inflammatory markers. The diet did not influence the inflammatory markers C-reactive protein, TNFα, IL6, or IL12. In addition, n3 fatty acids attenuated the increase in inflammatory adipose tissue CD16–CD14+ macrophages induced by high palm oil. High-fat diets with and without n3 fatty acids both induced hyperglycemia without hyperinsulinemia. The high-fat only group but not the high-fat group with n3 fatty acids showed reduced insulin sensitivity in response to insulin challenge. This effect was not mediated by decreased phosphorylation of protein kinase B. Therefore, in obese Ossabaw swine, n3 fatty acids partially attenuate insulin resistance but only marginally change inflammatory status and macrophage phenotype in adipose tissue. PMID:23561883

Radioiodine Labeled Anti-MIF McAb: A Potential Agent for Inflammation Imaging

PubMed Central

Zhang, Chao; Hou, Gui-hua; Han, Jian-kui; Song, Jing; Liang, Ting

2007-01-01

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with NaI125 by Iodogen method. Animal models were induced in the mice by intramuscular injection of S. aureus, E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of I125-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found in S. aureus group and the lowest was in E. coli group. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders. PMID:18317509

Intestinal alkaline phosphatase and sodium butyrate may be beneficial in attenuating LPS-induced intestinal inflammation.

PubMed

Melo, A D B; Silveira, H; Bortoluzzi, C; Lara, L J; Garbossa, C A P; Preis, G; Costa, L B; Rostagno, M H

2016-10-17

In this study, we evaluated the effect of intestinal alkaline phosphatase (IAP) and sodium butyrate (NaBu) on lipopolysaccharide (LPS)-induced intestinal inflammation. Intestinal alkaline phosphatase and RelA/p65 (NF-κB) gene expressions in porcine jejunum explants were evaluated following exposure to sodium butyrate (NaBu) and essential oil from Brazilian red pepper (EO), alone or in combination with NaBu, as well as exogenous IAP with or without LPS challenge. Five piglets weighing approximately 20 kg each were sacrificed, and their jejunum were extracted. The tissues were segmented into 10 parts, which were exposed to 10 treatments. Gene expressions of IAP and RelA/p65 (NF-κB) in jejunal explants were evaluated via RT-PCR. We found that EO, NaBu, and exogenous IAP were able to up-regulate endogenous IAP and enhance RelA/p65 (NF-κB) gene expression. However, only NaBu and exogenous IAP down-regulated LPS-induced inflammatory response via RelA/p65 (NF-κB). In conclusion, we demonstrated that exogenous IAP and NaBu may be beneficial in attenuating LPS-induced intestinal inflammation.

A Dietary Mixture Containing Fish Oil, Resveratrol, Lycopene, Catechins, and Vitamins E and C Reduces Atherosclerosis in Transgenic Mice123

PubMed Central

Verschuren, Lars; Wielinga, Peter Y.; van Duyvenvoorde, Wim; Tijani, Samira; Toet, Karin; van Ommen, Ben; Kooistra, Teake; Kleemann, Robert

2011-01-01

Chronic inflammation and proatherogenic lipids are important risk factors of cardiovascular disease (CVD). Specific dietary constituents such as polyphenols and fish oils may improve cardiovascular risk factors and may have a beneficial effect on disease outcomes. We hypothesized that the intake of an antiinflammatory dietary mixture (AIDM) containing resveratrol, lycopene, catechin, vitamins E and C, and fish oil would reduce inflammatory risk factors, proatherogenic lipids, and endpoint atherosclerosis. AIDM was evaluated in an inflammation model, male human C-reactive protein (CRP) transgenic mice, and an atherosclerosis model, female ApoE*3Leiden transgenic mice. Two groups of male human-CRP transgenic mice were fed AIDM [0.567% (wt:wt) powder and 0.933% (wt:wt oil)] or placebo for 6 wk. The effects of AIDM on basal and IL-1β–stimulated CRP expression were investigated. AIDM reduced cytokine-induced human CRP and fibrinogen expression in human-CRP transgenic mice. In the atherosclerosis study, 2 groups of female ApoE*3Leiden transgenic mice were fed an atherogenic diet supplemented with AIDM [0.567% (wt:wt) powder and 0.933% (wt:wt oil)] or placebo for 16 wk. AIDM strongly reduced plasma cholesterol, TG, and serum amyloid A concentrations compared with placebo. Importantly, long-term treatment of ApoE*3Leiden mice with AIDM markedly reduced the development of atherosclerosis by 96% compared with placebo. The effect on atherosclerosis was paralleled by a reduced expression of the vascular inflammation markers and adhesion molecules inter-cellular adhesion molecule-1 and E-selectin. Dietary supplementation of AIDM improves lipid and inflammatory risk factors of CVD and strongly reduces atherosclerotic lesion development in female transgenic mice. PMID:21411607

Lemongrass (Cymbopogon flexuosus) essential oil demonstrated anti-inflammatory effect in pre-inflamed human dermal fibroblasts.

PubMed

Han, Xuesheng; Parker, Tory L

2017-06-01

Lemongrass ( Cymbopogon flexuosus ) essential oil (LEO), which has citral as its main component, has exhibited anti-inflammatory effect in both animal and human cells. In this study, we evaluated the anti-inflammatory activity of a commercially available LEO in pre-inflamed human dermal fibroblasts. We first studied the impact of LEO on 17 protein biomarkers that are critically associated with inflammation and tissue remodeling. LEO significantly inhibited production of the inflammatory biomarkers vascular cell adhesion molecule 1 (VCAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG); decreased levels of the tissue remodeling biomarkers collagen-I and III, epidermal growth factor receptor (EGFR), and plasminogen activator inhibitor (PAI-1); and inhibited the immunomodulatory biomarker macrophage colony-stimulating factor (M-CSF). Furthermore, we studied the impact of LEO on genome-wide gene expression profiles. LEO significantly modulated global gene expression and robustly impacted signaling pathways, many of which are critical for inflammation and tissue remodeling processes. This study provides the first evidence of the anti-inflammatory activity of LEO in human skin cells and indicates that it is a good therapeutic candidate for treating inflammatory conditions of the skin.

3. Photocopied October 1976, from Theoph Schramke, Description of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Photocopied October 1976, from Theoph Schramke, Description of the New York Croton Aqueduct, New York: New York, 1843. PLATE VI, SING SING KILL BRIDGE. - Old Croton Aqueduct, Sing Sing Kill Bridge, Spanning Aqueduct Street & Broadway, Ossining, Westchester County, NY

Assessment of blood flow with 68Ga-DOTA PET in experimental inflammation: a validation study using 15O-water

PubMed Central

Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

2014-01-01

Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N‘,N‘‘,N‘‘‘-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog (68Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 15O) and 30-min 68Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 15O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of 68Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the 68Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 15O-based blood flow and 68Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that 68Ga-DOTA PET imaging is useful for the quantification of increased blood flow induced by inflammation. PMID:25250206

Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: a validation study using (15)O-water.

PubMed

Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

2014-01-01

Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog ((68)Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 (15)O) and 30-min (68)Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 (15)O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of (68)Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the (68)Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 (15)O-based blood flow and (68)Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that (68)Ga-DOTA PET imaging is useful for the quantification of increased blood flow induced by inflammation.

Hepatoprotective activity of dried- and fermented-processed virgin coconut oil.

PubMed

Zakaria, Z A; Rofiee, M S; Somchit, M N; Zuraini, A; Sulaiman, M R; Teh, L K; Salleh, M Z; Long, K

2011-01-01

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study.

Hepatoprotective Activity of Dried- and Fermented-Processed Virgin Coconut Oil

PubMed Central

Zakaria, Z. A.; Rofiee, M. S.; Somchit, M. N.; Zuraini, A.; Sulaiman, M. R.; Teh, L. K.; Salleh, M. Z.; Long, K.

2011-01-01

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study. PMID:21318140

Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium

PubMed Central

Wang, Hang; Li, Tsung-Lin; Hsia, Simon; Su, I-Li; Chan, Yi-Lin; Wu, Chang-Jer

2015-01-01

Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy. PMID:25797259

Identification of a Novel Topoisomerase Inhibitor Effective in Cells Overexpressing Drug Efflux Transporters

PubMed Central

Fayad, Walid; Fryknäs, Mårten; Brnjic, Slavica; Olofsson, Maria Hägg; Larsson, Rolf; Linder, Stig

2009-01-01

Background Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology. Method and Findings A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak and Bax, mitochondrial cytochrome c release and mitochondrial membrane permeabilization in HCT116 cells. Analysis of the gene expression signature of thaspine-treated cells suggested that thaspine is a topoisomerase inhibitor. Inhibition of both topoisomerase I and II was observed using in vitro assays, and thaspine was found to have a reduced cytotoxic effect on a cell line with a mutated topoisomerase II enzyme. Interestingly, in contrast to the topoisomerase II inhibitors doxorubicin, etoposide and mitoxantrone, thaspine was cytotoxic to cell lines overexpressing the PgP or MRP drug efflux transporters. We finally show that thaspine induces wide-spread apoptosis in colon carcinoma multicellular spheroids and that apoptosis is induced in two xenograft mouse models in vivo. Conclusions The alkaloid thaspine from the cortex of Croton lechleri is a dual topoisomerase inhibitor effective in cells overexpressing drug efflux transporters and induces wide-spread apoptosis in multicellular spheroids. PMID:19798419

Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines.

PubMed

Montopoli, Monica; Bertin, Riccardo; Chen, Zheng; Bolcato, Jenny; Caparrotta, Laura; Froldi, Guglielmina

2012-12-18

Croton lechleri Mull. Arg. (Euphorbiaceae) is a traditional medicinal plant which produces a red sap, traditionally known as "Sangre de Drago"; it is used in folk medicine externally for wounds, fractures, and haemorrhoids, internally for intestinal and stomach ulcers and also for the empirical cure of cancers. We investigated the effects of Croton lechleri sap and taspine in comparison with taxol and vinblastine on the growth of human cancer cell lines of SK23 (melanoma), LoVo and HT29 (colorectal cancer) using MTT and Trypan blue assays. Further, we studied cell cycle by flow cytometry and detected acetylated-α-tubulin by confocal microscope. Croton lechleri inhibited cell proliferation starting from 1 μg/mL in SK23 cells, whereas 10 times higher concentrations were required for growth inhibition of HT-29 and LoVo cell lines. Also taspine (0.1 μg/mL) inhibited the SK23 and HT29 cell proliferation. Further, assay was assessed on SK23 and HT29 cell lines with 24-48 h treatment with sap and taspine. Both sap and taspine inhibited cancer cell proliferation; taspine showed higher activity on SK23 cells, which was significantly increased after 48 h of SK23 treatment. Using confocal microscopy we observed that Croton lechleri (1 μg/mL) caused a loss of microtubule structure, whereas taspine (0.5 μg/mL) caused an increase in acetylated α-tubulin and a modification of cellular morphology, mainly in SK23 cells. Croton lechleri sap 10 and 50 μg/mL influence cell cycle; 50 μg/mL sap caused a dramatic reduction of cells in G(1)/G(0) and S phases with a great increase of subG(0) cells. The data showed that Croton lechleri and taspine could inhibit cell proliferation with higher potency against melanoma SK23 cells, supporting the empirical use of the sap as anticancer in ethnomedicine and taspine as a possible anticancer agent. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Crotonic acid as a bioactive factor in carrot seeds (Daucus carota L.).

PubMed

Jasicka-Misiak, Izabela; Wieczorek, Piotr P; Kafarski, Paweł

2005-06-01

Water extracts from the carrot seed (Daucus carota L.) var. Perfekcja exhibit plant growth inhibitory properties against cress, cucumber, onion and carrot in a dose-dependant manner. This property results from the action of low-and high-molecular components of the extract. The low-molecular component was identified as crotonic acid ((E)-2-butenoic acid). Its presence was also confirmed in other late varieties of carrot. The determined strong herbicidal properties of crotonic acid and its availability after release to soil combined with its high level in seeds suggest that it might be considered as an allelopathic and autotoxic factor in the seeds.

Dietary Lipid Type, Rather Than Total Number of Calories, Alters Outcomes of Enteric Infection in Mice.

PubMed

DeCoffe, Daniella; Quin, Candice; Gill, Sandeep K; Tasnim, Nishat; Brown, Kirsty; Godovannyi, Artem; Dai, Chuanbin; Abulizi, Nijiati; Chan, Yee Kwan; Ghosh, Sanjoy; Gibson, Deanna L

2016-06-01

Dietary lipids modulate immunity, yet the means by which specific fatty acids affect infectious disease susceptibility remains unclear. Deciphering lipid-induced immunity is critical to understanding the balance required for protecting against pathogens while avoiding chronic inflammatory diseases. To understand how specific lipids alter susceptibility to enteric infection, we fed mice isocaloric, high-fat diets composed of corn oil (rich in n-6 polyunsaturated fatty acids [n-6 PUFAs]), olive oil (rich in monounsaturated fatty acids), or milk fat (rich in saturated fatty acids) with or without fish oil (rich in n-3 PUFAs). After 5 weeks of dietary intervention, mice were challenged with Citrobacter rodentium, and pathological responses were assessed. Olive oil diets resulted in little colonic pathology associated with intestinal alkaline phosphatase, a mucosal defense factor that detoxifies lipopolysaccharide. In contrast, while both corn oil and milk fat diets resulted in inflammation-induced colonic damage, only milk fat induced compensatory protective responses, including short chain fatty acid production. Fish oil combined with milk fat, unlike unsaturated lipid diets, had a protective effect associated with intestinal alkaline phosphatase activity. Overall, these results reveal that dietary lipid type, independent of the total number of calories associated with the dietary lipid, influences the susceptibility to enteric damage and the benefits of fish oil during infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

40 CFR 180.341 - 2,4-Dinitro-6-octylphenyl crotonate and 2,6-dinitro-4-octylphenyl crotonate; tolerances for...

Code of Federal Regulations, 2011 CFR

2011-07-01

... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.341 2,4-Dinitro-6-octylphenyl... established for combined negligible residues of a fungicide and insecticide that is a mixture of 2,4-dinitro-6...

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6.

PubMed

Tron, Kyrylo; Novosyadlyy, Ruslan; Dudas, Jozsef; Samoylenko, Anatoly; Kietzmann, Thomas; Ramadori, Giuliano

2005-03-01

Heme oxygenase-1 (HO-1) is the inducible isoform of an enzyme family responsible for heme degradation and was suggested to be involved in the acute phase response in the liver. However, the mechanisms of the HO-1 regulation under inflammatory conditions are poorly understood. Therefore, the purpose of the current work was to study the expression of HO-1 in the liver and other organs of rats with a localized inflammation after intramuscular injection of turpentine oil (TO). Since interleukin-6 (IL-6) is known to be a principal mediator of inflammation, the levels of this cytokine were also estimated in the animal model used. HO-1 and IL-6 expression was evaluated by Northern blot, in situ hybridization, Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. In the liver and injured muscle, the HO-1 mRNA levels were dramatically increased 4-6 h after TO administration. HO-1 protein levels in the liver were elevated starting from 6-12 h after the treatment. In other internal organs such as the heart, kidney and large intestine, only a slight induction of HO-1 mRNA was observed. IL-6-specific transcripts appeared only in the injured muscle and were in accordance with serum levels of IL-6. In turn, temporal expression of IL-6 in the muscle and circulatory IL-6 levels correlated well with HO-1 expression in the liver and injured muscle. In the liver of control rats HO-1 protein was detected in Kupffer cells, while in TO-injected rats also hepatocytes became strongly HO-1 positive. Conversely, in the injured muscle, HO-1 immunoreactivity was attributed only to macrophages. Our data demonstrate that during localized inflammation HO-1 expression was rapidly and strongly induced in macrophages of injured muscle and in hepatocytes, and IL-6 derived from injured muscle seems to be responsible for the HO-1 induction in the liver.

Evaluation of the antioedematogenic, free radical scavenging and antimicrobial activities of aerial parts of Tillandsiastreptocarpa Baker-Bromeliaceae.

PubMed

Delaporte, R H; Sarragiotto, M H; Takemura, O S; Sánchez, G M; Filho, B P D; Nakamura, C V

2004-12-01

The crude methanolic extract of the aerial parts of Tillandsiastreptocarpa was investigated for their acute toxicity and antioedematogenic, antioxidant and antimicrobial activities. Also, the antioedematogenic activity of the hexane fraction resulting from the partition of the crude methanolic extract was evaluated. The methanolic extract and the hexane fraction showed significant (P < 0.05) inhibition of ear oedema, observed at 2 mg/ear in the croton oil-induced mice ear oedema test. In the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging test, a high reactivity and potent antioxidant effect (IC(50) = 0.0056%, w/v) were observed for the methanolic extract. The antimicrobial activity assay showed that the crude methanolic extract was inactive toward Escherichiacoli, Staphylococcusaureus, Pseudomonasaeruginosa, Bacillussubtilis, Candidaalbicans, C. parapsilosis, C. krusei and C. tropicalis (MIC > 500 microg/ml). The methanolic extract showed no toxic effect on mice at a single dose of 2000 mg/kg (p.o). Common side effects including mild diarrhoea, loss of weight and depression were not recorded. The compounds cycloartenol, 4',5-dihydroxy-3',7-dimethoxyflavanone and a mixture of the steroids stigmasterol, beta-sitosterol and campesterol, were isolated from the hexane fraction and identified by spectroscopic methods.

Extra-Virgin Olive Oil with Natural Phenolic Content Exerts an Anti-Inflammatory Effect in Adipose Tissue and Attenuates the Severity of Atherosclerotic Lesions in Ldlr-/-.Leiden Mice.

PubMed

Luque-Sierra, Amparo; Alvarez-Amor, Leticia; Kleemann, Robert; Martín, Franz; Varela, Lourdes M

2018-05-15

The present study investigates the effect of olive oils with different phenolic content in high-fat diets (HFDs) on hypertrophy and inflammation in adipose tissue and associated atherosclerosis, in the context of obesity. Ldlr-/-.Leiden mice were fed three different HFDs for 32 weeks and were compared with mice fed the standard low-fat diet (LFD). The different fats provided in the HFDs were lard (HFD-L), extra-virgin olive oil (EVOO; 79 mg kg -1 of phenolic compounds, HFD-EVOO), or EVOO rich in phenolic compounds (OL, 444 mg kg -1 of phenolic compounds, HFD-OL). All HFD-fed mice became obese, but only HFD-L-induced adipocyte hypertrophy. HFD-EVOO mice exhibited the greatest levels of Adiponectin in adipose tissue and presented atherosclerotic lesions similar to the LFD group, with a very low count of monocyte/macrophage compared with HFD-L and HFD-OL mice. Enrichment of the phenolic content of olive oil reduced the secretion of nitrites/nitrates in the aorta, but atherosclerosis was not attenuated in HFD-OL mice compared to other HFD mice. Consumption of olive oil with a natural content of phenolic compounds attenuates adipose tissue hypertrophy and inflammation and exerts antiatherosclerotic effects in mice. A higher phenolic content of olive oil did not provide further benefits in the prevention of atherosclerosis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Topical lavender oil for the treatment of recurrent aphthous ulceration.

PubMed

Altaei, D Tagreed

2012-02-01

To determine the laboratory and clinical efficacy of lavender oil in the treatment of recurrent aphthous ulceration (RAU). This was a randomized double-blind, placebo-controlled study performed firstly to treat the induced ulcers by different methods in experimental animals (rabbits) treated with lavender oil or placebo. Clinical and histological healing was established by measuring the area of the ulcer and inflammation levels in each test group. Secondly, safety/toxicity; the median lethal dose (LD50) was studied in albino mice, and dermal irritation test was performed by primary irritation to the skin and measured by a patch-test technique on the intact skin of the albino rabbit. Thirdly, antibacterial effect; lavender oil was screened against bacteria obtained from swab specimen of human subjects' RAU using disc diffusion method. Fourthly, clinical study; 115 subjects (mean age 38 years, mean weight 75 kg) were divided into two groups of subjects topically treated with lavender oil or placebo. The clinical efficacy was assessed by inflammation level, erythema, edema, ulcer duration, ulcer size, mean area under the curve of ulcer area, healing time, and associated pain intensity and reduction. Animals treated with lavender oil showed a significant ulcer size reduction, increased rate of mucosal repair, and healing within 3 days of treatment compared to baseline and placebo groups [2-3 days (90%), 4 days (10%)] (P=0.001). The intraperitoneal LD50 value in mice was 6.5 gm/kg; clinical dermal irritation test showed no sign of irritation in the tested products. Lavender oil showed a broad antibacterial activity against all tested strains; it exhibited significant inhibition on tested bacteria where the value of zone of inhibition ranged from 14.5-24 mm vs Streptomycin (25 microg/disc) 12-22 +/- 0.5 mm; MIC was > 6.4-36 mg/ml. RAU patients treated with lavender oil showed a significant reduction in inflammation level, ulcer size, healing time, from 2-4 days [2 days (40%), 3 days (50%), 4 days (10%)], and pain relief mostly from the first dose, compared to baseline and placebo. No side effects were reported.

Chemical composition and anti-inflammatory activities of the essential oils from Acacia mearnsii de Wild.

PubMed

Avoseh, Opeyemi N; Oyedeji, Ope-oluwa O; Aremu, Kayode; Nkeh-Chungag, Benedicta N; Songca, Sandile P; Oluwafemi, Samuel O; Oyedeji, Adebola O

2015-01-01

The volatile oils of the leaves and the stem bark of Acacia mearnsii de Wild obtained by hydro-distillation were analysed by gas chromatography-mass spectrometry. A total of 20, 38, 29 and 38 components accounted for 93.8%, 92.1%, 78.5% and 90.9% of the total oils of the fresh, dry leaves and fresh, dry stem bark, respectively. The major components of the oil were octadecyl alcohol (25.5%) and phytol (10.5%); cis-verbenol (29.5%); phytol (10.1%) and phytol (23.4%) for the fresh leaves, dried leaves, fresh stem, dry stem bark, respectively. Oral administration of essential oils at a dose of 2% showed significant (p < 0.05) anti-inflammatory properties in the albumin-induced test model in rats. Oils from the fresh leaves and dry stems inhibited inflammation beyond 4 h post treatment. The potent anti-inflammatory activity of essential oils of A. mearnsii hereby confirmed its traditional use in treating various inflammatory diseases.

21 CFR 175.350 - Vinyl acetate/crotonic acid copolymer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vinyl acetate/crotonic acid copolymer. 175.350 Section 175.350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF...

Hepatic Regeneration and Reno-Protection by Fish oil, Nigella sativa Oil and Combined Fish Oil/Nigella sativa Volatiles in CCl4 Treated Rats.

PubMed

Al-Okbi, Sahar Y; Mohamed, Doha A; Hamed, Thanaa E; Edris, Amr E; Fouda, Karem

2018-03-01

The aim of the present research was to investigate the effect of fish oil, crude Nigella sative oil and combined fish oil/Nigella sative volatile oil as hepato-regenerative and renal protective supplements. The oils were administered as emulsions to rat model with liver injury induced by CCl 4 . Plasma activities of transaminases (AST and ALT) were evaluated as liver function indicators, while plasma creatinine and urea and creatinine clearance were determined as markers of kidney function. Plasma malondialdehyde (MDA), nitrite (NO) and tumor necrosis factor-α (TNF-α) were estimated to assess the exposure to oxidative stress and subsequent inflammation. Liver fat was extracted and their fatty acids´ methyl esters were determined using gas chromatography. Results showed that plasma activities of AST and ALT were significantly higher in CCl 4 control group compared to control healthy group. Plasma levels of creatinine and urea increased significantly in CCl 4 control, while creatinine clearance was reduced significantly in the same group. All rat treated groups given the three oil emulsions showed improvement in liver function pointing to the initiation of liver regeneration. The combination of fish oil/Nigella sative volatiles showed the most promising regenerative activity. Oxidative stress and inflammation which were increased significantly in CCl 4 control group showed improvement on administration of the three different oil emulsions. Fatty acids methyl ester of liver fat revealed that rats treated with fish oil/Nigella sative volatile oil presented the highest content of unsaturated fatty acids (45.52% ± 0.81) while fish oil showed the highest saturated fatty acids (53.28% ± 1.68). Conclusion; Oral administration of oil emulsions of native fish oil, Nigella sative crude oil and combined fish oil/Nigella sative volatile oil reduced liver and kidney injury in rat model of CCl 4 through exerting anti-inflammatory and antioxidant activity. Fish oil/Nigella sative volatile oil emulsion was the most promising hepato-regenerative and reno-protective formula among the different groups.

Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation.

PubMed

Andersen, Hjalte H; Lo Vecchio, Silvia; Gazerani, Parisa; Arendt-Nielsen, Lars

2017-09-01

Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as "mustard oil") has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose-response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. In addition, a comprehensive battery of quantitative sensory tests was conducted, including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was quantified using full-field laser perfusion imaging. Erythema and hyperpigmentation were assessed before, immediately after, and ≈64 hours after AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia, and dynamic mechanical allodynia (P < 0.05). No significant differences in induced pain hypersensitivity were observed between the 50% and 90% AITC concentrations. Acute and prolonged inflammation was evoked by all concentrations, and assessments by full-field laser perfusion imaging demonstrated a significant dose-dependent increase with a ceiling effect from 50% to 90%. Topical AITC application produces pain and somatosensory sensitization in a dose-dependent manner with optimal concentrations recommended to be >10% and ≤50%. The model is translatable to humans and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics, and anti-inflammatory compounds or for exploratory clinical purposes, eg, loss- or gain-of-function in peripheral neuropathies.

Ozone-Induced Responses in Croton floribundus Spreng. (Euphorbiaceae): Metabolic Cross-Talk between Volatile Organic Compounds and Calcium Oxalate Crystal Formation

PubMed Central

Cardoso-Gustavson, Poliana; Bolsoni, Vanessa Palermo; de Oliveira, Debora Pinheiro; Guaratini, Maria Tereza Gromboni; Aidar, Marcos Pereira Marinho; Marabesi, Mauro Alexandre; Alves, Edenise Segala; de Souza, Silvia Ribeiro

2014-01-01

Here, we proposed that volatile organic compounds (VOC), specifically methyl salicylate (MeSA), mediate the formation of calcium oxalate crystals (COC) in the defence against ozone (O3) oxidative damage. We performed experiments using Croton floribundus, a pioneer tree species that is tolerant to O3 and widely distributed in the Brazilian forest. This species constitutively produces COC. We exposed plants to a controlled fumigation experiment and assessed biochemical, physiological, and morphological parameters. O3 induced a significant increase in the concentrations of constitutive oxygenated compounds, MeSA and terpenoids as well as in COC number. Our analysis supported the hypothesis that ozone-induced VOC (mainly MeSA) regulate ROS formation in a way that promotes the opening of calcium channels and the subsequent formation of COC in a fast and stable manner to stop the consequences of the reactive oxygen species in the tissue, indeed immobilising the excess calcium (caused by acute exposition to O3) that can be dangerous to the plant. To test this hypothesis, we performed an independent experiment spraying MeSA over C. floribundus plants and observed an increase in the number of COC, indicating that this compound has a potential to directly induce their formation. Thus, the tolerance of C. floribundus to O3 oxidative stress could be a consequence of a higher capacity for the production of VOC and COC rather than the modulation of antioxidant balance. We also present some insights into constitutive morphological features that may be related to the tolerance that this species exhibits to O3. PMID:25165889

Mitochondria-dependent apoptogenic activity of the aqueous root extract of Croton membranaceus against human BPH-1 cells.

PubMed

Afriyie, D K; Asare, G A; Bugyei, K; Lin, J; Peng, J; Hong, Z

2015-01-15

Croton membranaceus aqueous root extract (CMARE) is among the widely used phytotherapeutics in Ghana for the management of benign prostatic hyperplasia (BPH) and prostate cancer. However, the mechanism of action of CMARE remains to be elucidated. This study aimed to establish whether apoptosis is involved in the antiproliferative effect of CMARE on human BPH-1 cells. We determined the effect of treatment with 0, 1, 3, and 5 mg/mL CMARE for 24, 48, and 72 h on the viability and morphology of BPH-1 cells using the MMT assay and phase-contrast microscopy, respectively. We examined the apoptosis-inducing effects of CMARE after 48 h at the cellular level using Hoescht 33258 and JC-1 dye staining and flow cytometry analysis. We performed reverse transcription polymerase chain reaction and Western blotting to confirm the apoptotic effects of CMARE at the molecular level. CMARE induced a significant dose-dependent inhibition in the proliferation of BPH-1 cells (P < 0.05) and an alteration in their morphology and a reduction their density. Furthermore, CMARE induced dose-dependent staining of the nuclear chromatin, significant DNA fragmentation with G₀/G₁ sub-diploid cells (P < 0.01), and loss of the mitochondrial membrane potential in the treated cells compared to the controls after 48 h (P < 0.01). Additionally, while CMARE induced a significant upregulation of the mRNA and protein levels of Bax, those of Bcl2 did not change significantly. Therefore, induction of mitochondria-dependent apoptosis of BPH-1 cells may be a possible mechanism of action of CMARE.

Flavonoids from the stems of Croton caudatus Geisel. var. tomentosus Hook.

PubMed

Zou, Guo-An; Su, Zhi-Heng; Zhang, Hong-Wu; Wang, Yuan; Yang, Jun-Shan; Zou, Zhong-Mei

2010-02-26

A new flavone, named crotoncaudatin (1), was isolated from the stems of Croton caudatus Geisel. var. tomentosus Hook., together with nine known analogues: 3,5,6,7,8,3',4'-heptamethoxyflavone (2), tangeretin (3), nobiletin (4), 5,6,7,4'-tetramethoxy-flavone (5), sinensetin (6), kaempferol (7), tiliroside (8), kaempferol-3-O-rutinoside (9) and rutin (10). The structures of the above compounds were established by a combination of spectroscopic methods, including HR-ESI-MS, 1H-NMR, 13C-NMR, HMQC and HMBC spectra. All compounds were isolated from and identified in this species for the first time and compounds 1-6 are new for the genus Croton.

Arborvitae (Thuja plicata) essential oil significantly inhibited critical inflammation- and tissue remodeling-related proteins and genes in human dermal fibroblasts.

PubMed

Han, Xuesheng; Parker, Tory L

2017-06-01

Arborvitae ( Thuja plicata ) essential oil (AEO) is becoming increasingly popular in skincare, although its biological activity in human skin cells has not been investigated. Therefore, we sought to study AEO's effect on 17 important protein biomarkers that are closely related to inflammation and tissue remodeling by using a pre-inflamed human dermal fibroblast culture model. AEO significantly inhibited the expression of vascular cell adhesion molecule 1 (VCAM-1), intracellular cell adhesion molecule 1 (ICAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell chemoattractant (I-TAC), monokine induced by interferon gamma (MIG), and macrophage colony-stimulating factor (M-CSF). It also showed significant antiproliferative activity and robustly inhibited collagen-I, collagen-III, plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2). The inhibitory effect of AEO on increased production of these protein biomarkers suggests it has anti-inflammatory property. We then studied the effect of AEO on the genome-wide expression of 21,224 genes in the same cell culture. AEO significantly and diversely modulated global gene expression. Ingenuity pathway analysis (IPA) showed that AEO robustly affected numerous critical genes and signaling pathways closely involved in inflammatory and tissue remodeling processes. The findings of this study provide the first evidence of the biological activity and beneficial action of AEO in human skin cells.

Force of habit: shrubs, trees and contingent evolution of wood anatomical diversity using Croton (Euphorbiaceae) as a model system

PubMed Central

van Ee, Benjamin W.; Riina, Ricarda; Berry, Paul E.; Wiedenhoeft, Alex C.

2017-01-01

Abstract Background and Aims Wood is a major innovation of land plants, and is usually a central component of the body plan for two major plant habits: shrubs and trees. Wood anatomical syndromes vary between shrubs and trees, but no prior work has explicitly evaluated the contingent evolution of wood anatomical diversity in the context of these plant habits. Methods Phylogenetic comparative methods were used to test for contingent evolution of habit, habitat and wood anatomy in the mega-diverse genus Croton (Euphorbiaceae), across the largest and most complete molecular phylogeny of the genus to date. Key Results Plant habit and habitat are highly correlated, but most wood anatomical features correlate more strongly with habit. The ancestral Croton was reconstructed as a tree, the wood of which is inferred to have absent or indistinct growth rings, confluent-like axial parenchyma, procumbent ray cells and disjunctive ray parenchyma cell walls. The taxa sampled showed multiple independent origins of the shrub habit in Croton, and this habit shift is contingent on several wood anatomical features (e.g. similar vessel-ray pits, thick fibre walls, perforated ray cells). The only wood anatomical trait correlated with habitat and not habit was the presence of helical thickenings in the vessel elements of mesic Croton. Conclusions Plant functional traits, individually or in suites, are responses to multiple and often confounding contexts in evolution. By establishing an explicit contingent evolutionary framework, the interplay between habit, habitat and wood anatomical diversity was dissected in the genus Croton. Both habit and habitat influence the evolution of wood anatomical characters, and conversely, the wood anatomy of lineages can affect shifts in plant habit and habitat. This study hypothesizes novel putatively functional trait associations in woody plant structure that could be further tested in a variety of other taxa. PMID:28065919

Force of habit: shrubs, trees and contingent evolution of wood anatomical diversity using Croton (Euphorbiaceae) as a model system.

PubMed

Arévalo, Rafael; van Ee, Benjamin W; Riina, Ricarda; Berry, Paul E; Wiedenhoeft, Alex C

2017-03-01

Wood is a major innovation of land plants, and is usually a central component of the body plan for two major plant habits: shrubs and trees. Wood anatomical syndromes vary between shrubs and trees, but no prior work has explicitly evaluated the contingent evolution of wood anatomical diversity in the context of these plant habits. Phylogenetic comparative methods were used to test for contingent evolution of habit, habitat and wood anatomy in the mega-diverse genus Croton (Euphorbiaceae), across the largest and most complete molecular phylogeny of the genus to date. Plant habit and habitat are highly correlated, but most wood anatomical features correlate more strongly with habit. The ancestral Croton was reconstructed as a tree, the wood of which is inferred to have absent or indistinct growth rings, confluent-like axial parenchyma, procumbent ray cells and disjunctive ray parenchyma cell walls. The taxa sampled showed multiple independent origins of the shrub habit in Croton , and this habit shift is contingent on several wood anatomical features (e.g. similar vessel-ray pits, thick fibre walls, perforated ray cells). The only wood anatomical trait correlated with habitat and not habit was the presence of helical thickenings in the vessel elements of mesic Croton . Plant functional traits, individually or in suites, are responses to multiple and often confounding contexts in evolution. By establishing an explicit contingent evolutionary framework, the interplay between habit, habitat and wood anatomical diversity was dissected in the genus Croton . Both habit and habitat influence the evolution of wood anatomical characters, and conversely, the wood anatomy of lineages can affect shifts in plant habit and habitat. This study hypothesizes novel putatively functional trait associations in woody plant structure that could be further tested in a variety of other taxa. Published by Oxford University Press on behalf of the Annals of Botany Company 2017. This work is written by US Government employees and is in the public domain in the US.

Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets.

PubMed

Lecomte, Manon; Couëdelo, Leslie; Meugnier, Emmanuelle; Loizon, Emmanuelle; Plaisancié, Pascale; Durand, Annie; Géloën, Alain; Joffre, Florent; Vaysse, Carole; Michalski, Marie-Caroline; Laugerette, Fabienne

2017-05-01

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats.

PubMed

Serafine, Katherine M; Labay, Caitlin; France, Charles P

2016-08-01

Eating a diet high in fat can lead to obesity, chronic metabolic disease, and increased inflammation in both the central and peripheral nervous systems. Dietary supplements that are high in omega-3 polyunsaturated fatty acids can reduce or prevent these negative health consequences in rats. Eating high fat chow also increases the sensitivity of rats to behavioral effects of drugs acting on dopamine systems (e.g., cocaine), and this effect is greatest in adolescent females. The present experiment tested the hypothesis that dietary supplementation with fish oil prevents high fat chow induced increases in sensitivity to cocaine in adolescent female rats. Female Sprague-Dawley rats (post-natal day 25-27) ate standard laboratory chow (5.7% fat), high fat chow (34.4% fat), or high fat chow supplemented with fish oil (20% w/w). Cocaine dose dependently (1-17.8mg/kg) increased locomotion and induced sensitization across 6 weeks of once-weekly testing in all rats; however, these effects were greatest in rats eating high fat chow. Dietary supplementation with fish oil prevented enhanced locomotion and sensitization in rats eating high fat chow. There were no differences in inflammatory markers in plasma or the hypothalamus among dietary conditions. These results demonstrate that dietary supplementation with fish oil can prevent high fat diet-induced sensitization to cocaine, but they fail to support the view that these effects are due to changes in proinflammatory cytokines. These data add to a growing literature on the relationship between diet and drug abuse and extend the potential health benefits of fish oil to stimulant drug abuse prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats

PubMed Central

Serafine, Katherine M.; Labay, Caitlin; France, Charles P.

2016-01-01

BACKGROUND Eating a diet high in fat can lead to obesity, chronic metabolic disease, and increased inflammation in both the central and peripheral nervous systems. Dietary supplements that are high in omega-3 polyunsaturated fatty acids can reduce or prevent these negative health consequences in rats. Eating high fat chow also increases the sensitivity of rats to behavioral effects of drugs acting on dopamine systems (e.g., cocaine), and this effect is greatest in adolescent females. METHODS The present experiment tested the hypothesis that dietary supplementation with fish oil prevents high fat chow induced increases in sensitivity to cocaine in adolescent female rats. Female Sprague-Dawley rats (post-natal day 25–27) ate standard laboratory chow (5.7% fat), high fat chow (34.4% fat), or high fat chow supplemented with fish oil (20% w/w). Cocaine dose dependently (1–17.8 mg/kg) increased locomotion and induced sensitization across 6 weeks of once-weekly testing in all rats; however, these effects were greatest in rats eating high fat chow. RESULTS Dietary supplementation with fish oil prevented enhanced locomotion and sensitization in rats eating high fat chow. There were no differences in inflammatory markers in plasma or the hypothalamus among dietary conditions. CONCLUSIONS These results demonstrate that dietary supplementation with fish oil can prevent high fat diet-induced sensitization to cocaine, but they fail to support the view that these effects are due to changes in proinflammatory cytokines. These data add to a growing literature on the relationship between diet and drug abuse and extend the potential health benefits of fish oil to stimulant drug abuse prevention. PMID:27242289

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation.

PubMed

Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

2008-02-01

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40-60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs-Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL.

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation

PubMed Central

Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

2008-01-01

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40–60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs–Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL. PMID:18197871

Inflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice.

PubMed

Sukumaran, Abitha; Venkatraman, Aparna; Jacob, Molly

2012-06-15

Anemia of inflammation is characterized by disturbances in systemic iron homeostasis. In order to better understand the events involved, we carried out a time-course study on the effects of acute and chronic inflammation on iron-related proteins in mouse splenic macrophages and the liver. Mice were sacrificed at various time points ranging from 0 h up to 4 weeks after induction of inflammation with turpentine oil. Expression levels of iron-related proteins in the splenic macrophages and liver were determined. Iron levels in the serum, spleen and liver were also measured. Hepatic hepcidin was found to be induced in response to inflammation. In the macrophages, expression levels of ferroportin and TfR1 were decreased at some of the time points. The expression of hepatic TfR1 and ferritin was significantly higher at the early time points. Ferritin levels in the liver decreased progressively thereafter; this was associated with significantly higher ferroportin expression in the liver, despite high levels of hepcidin, suggesting that hepcidin may not regulate ferroportin levels in the liver, unlike in the macrophages. The effects of hepcidin, thus, appeared to be tissue-specific. Serum iron levels were decreased initially; these then rose and were associated with decreasing iron levels in the liver and spleen. Thus, inflammation affected the expression levels of many proteins involved in iron homeostasis in splenic macrophages and the liver, with differences seen in the effects at these 2 sites. These effects are likely to contribute to the development of anemia of inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

[1-9-NαC]-crourorb A1 isolated from Croton urucurana latex induces G2/M cell cycle arrest and apoptosis in human hepatocarcinoma cells.

PubMed

de Matos Cândido-Bacani, Priscila; Ezan, Frédéric; de Oliveira Figueiredo, Patrícia; Matos, Maria de Fátima Cepa; Rodrigues Garcez, Fernanda; Silva Garcez, Walmir; Baffet, Georges

2017-05-05

[1-9-NαC]-crourorb A1 is a cyclic peptide isolated from Croton urucurana Baillon latex, found in midwestern Brazil, that has been shown to exert cytotoxic effects against a panel of cancer cell lines. However, the underlying mechanisms responsible for the crourorb A1-induced cytotoxicity in cancer cells remain unknown. In this study, the effects of crourorb A1 on the viability, apoptosis, cell cycle and migration of Huh-7 (human hepatocarcinoma) cells were investigated. We evaluated the viability of Huh-7 cells treated with crourorb A1 in 2D and 3D collagen cultures and found that cells in 3D culture exhibited increased resistance to crourorb A1 compared to cells in 2D culture (IC 50 : 62μg/ml versus 35.75μg/ml). Crourorb A1 treatment decreases the viability of Huh-7 cells in a dose- and time-dependent manner and is associated with the induction of apoptosis, in the absence of necrotic cells, through the activation of caspase-3/7 and increased expression of the pro-apoptotic proteins Bak, Bid, Bax, Puma, Bim, and Bad. The effects of crourorb A1 are also associated with G2/M phase cell cycle arrest and increases in cyclin-dependent kinase (CDK1) and cyclin B1 expression. A significant reduction in Huh-7 cell migration induced by crourorb A1 was also observed in the presence of mitomycin C. Finally, we showed that the JNK/MAP pathway, but not ERK signaling, is involved in crourorb A1-induced hepatocarcinoma cell mortality. Copyright © 2017 Elsevier B.V. All rights reserved.

The flavonoid apigenin from Croton betulaster Mull inhibits proliferation, induces differentiation and regulates the inflammatory profile of glioma cells.

PubMed

Coelho, Paulo L C; Oliveira, Mona N; da Silva, Alessandra B; Pitanga, Bruno P S; Silva, Victor D A; Faria, Giselle P; Sampaio, Geraldo P; Costa, Maria de Fatima D; Braga-de-Souza, Suzana; Costa, Silvia L

2016-11-01

This study aimed to investigate the antitumor and immunomodulatory properties of the flavonoid apigenin (5,7,4'-trihydroxyflavone), which was extracted from Croton betulaster Mull, in glioma cell culture using the high-proliferative rat C6 glioma cell line as a model. Apigenin was found to have the ability to reduce the viability and proliferation of C6 cells in a time-dependent and dose-dependent manner, with an IC50 of 22.8 µmol/l, 40 times lower than that of temozolomide (1000 µmol/l), after 72 h of apigenin treatment. Even after C6 cells were treated with apigenin for 48 h, high proportions of C6 cells entered apoptosis (39.56%) and autophagy (22%) as shown by flow cytometry using annexin V/propidium iodide and acridine orange staining, respectively. In addition, the flavonoid apigenin induced cell accumulation in the G0/G1 phase of the cell cycle and inhibited glioma cell migration efficiently. Moreover, apigenin induced astroglial differentiation and morphological changes in C6 cells, characterized by increased expression of glial fibrillary acidic protein and decreased expression of nestin protein, a typical marker of neuronal precursors. The immunomodulating effects of apigenin were also characterized by a change in the inflammatory profile as evidenced by a significant decrease in interleukin-10 and tumor necrosis factor production and increased nitric oxide levels. Because apigenin can induce differentiation, apoptosis, and autophagy, can alter the profile of cytokines involved in regulating the immune response, and can reduce the survival, growth, proliferation, and migration of C6 cells, this flavonoid may be considered a potential antitumor drug for the adjuvant treatment of malignant gliomas.

Assignment of fatty acid-beta-oxidizing syntrophic bacteria to Syntrophomonadaceae fam. nov. on the basis of 16S rRNA sequence analyses

NASA Technical Reports Server (NTRS)

Zhao, H.; Yang, D.; Woese, C. R.; Bryant, M. P.

1993-01-01

After enrichment from Chinese rural anaerobic digestor sludge, anaerobic, sporing and nonsporing, saturated fatty acid-beta-oxidizing syntrophic bacteria were isolated as cocultures with H2- and formate-utilizing Methanospirillum hungatei or Desulfovibrio sp. strain G-11. The syntrophs degraded C4 to C8 saturated fatty acids, including isobutyrate and 2-methylbutyrate. They were adapted to grow on crotonate and were isolated as pure cultures. The crotonate-grown pure cultures alone did not grow on butyrate in either the presence or the absence of some common electron acceptors. However, when they were reconstituted with M. hungatei, growth on butyrate again occurred. In contrast, crotonate-grown Clostridium kluyveri and Clostridium sticklandii, as well as Clostridium sporogenes, failed to grow on butyrate when these organisms were cocultured with M. hungatei. The crotonate-grown pure subcultures of the syntrophs described above were subjected to 16S rRNA sequence analysis. Several previously documented fatty acid-beta-oxidizing syntrophs grown in pure cultures with crotonate were also subjected to comparative sequence analyses. The sequence analyses revealed that the new sporing and nonsporing isolates and other syntrophs that we sequenced, which had either gram-negative or gram-positive cell wall ultrastructure, all belonged to the phylogenetically gram-positive phylum. They were not closely related to any of the previously known subdivisions in the gram-positive phylum with which they were compared, but were closely related to each other, forming a new subdivision in the phylum. We recommend that this group be designated Syntrophomonadaceae fam. nov.; a description is given.

[Pathologic skin changes in workers at electric and thermoelectric power plants].

PubMed

Kieć-Swierczyńska, M; Woźniak, H

1988-01-01

Dermatological examination was performed and epidermal tests using a routine set of allergens and metals (Cr, Co, Ni, Al, Cu, Ag, Zn, Hg, Fe) on 112 workers of power plants and thermal-electric power stations working at the stands characterized by a heavy dustiness (electro-filters operation, ash removal, deslagging, carburizing) and at the stands where dustiness was not so heavy but instead exposure to machine oils and greases (retors' operators, electromechanics, assemblers and welders) was remarkable. It was found that occupational exposure to chemicals resulted in skin inflammation in 7.1% of the examined persons. Machine oils and greases induced skin inflammation in 2.7% and occupational acne in 5.3% of workers. It was also observed that chromium compounds were the primary allergen in workers exposed to dusts (13.4% of sensitized persons) and in workers exposed to industrial greases and oils (8.0% of sensitized persons). Allergy to cobalt compounds prevailed among persons exposed to smears and oils. Single positive results of epidermal tests with the use of copper and silver were obtained. Moreover, data concerning the microelements content in fly-ashes are presented. Information on the frequency of the incidence of occupational skin diseases, sickness absenteeism due to dermatoses and on personal safety equipment which should be used by the workers of power industry plants are provided.

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota

PubMed Central

Liehr, Martin; Mereu, Alessandro; Pastor, Jose Javier; Quintela, Jose Carlos; Staats, Stefanie; Rimbach, Gerald; Ipharraguerre, Ignacio Rodolfo

2017-01-01

Subclinical chronic inflammation (SCI) is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE) and their control counterparts (C+) were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS) to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-). In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001) and decreased feed ingestion (p < 0.05) and weight gain (p < 0.05). These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05) and plasma recovery of mannitol (p < 0.05) compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01) in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05) in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function. PMID:28346507

Enhanced barrier functions and anti-inflammatory effect of cultured coconut extract on human skin.

PubMed

Kim, Soomin; Jang, Ji Eun; Kim, Jihee; Lee, Young In; Lee, Dong Won; Song, Seung Yong; Lee, Ju Hee

2017-08-01

Natural plant oils have been used as a translational alternative to modern medicine. Particularly, virgin coconut oil (VCO) has gained popularity because of its potential benefits in pharmaceutical, nutritional, and cosmetic applications. Cultured coconut extract (CCE) is an alternative end product of VCO, which undergoes a further bacterial fermentation process. This study aimed to investigate the effects of CCE on human skin. We analyzed the expression of skin barrier molecules and collagens after applying CCE on human explanted skin. To evaluate the anti-inflammatory properties of CCE, the expression of inflammatory markers was analyzed after ultraviolet B (UVB) irradiation. The CCE-treated group showed increased expression of cornified cell envelope components, which contribute to protective barrier functions of the stratum corneum. Further, the expression of inflammatory markers was lower in the CCE-treated group after exposure to UVB radiation. These results suggest an anti-inflammatory effect of CCE against UVB irradiation-induced inflammation. Additionally, the CCE-treated group showed increased collagen and hyaluronan synthase-3 expression. In our study, CCE showed a barrier-enhancing effect and anti-inflammatory properties against ex vivo UVB irradiation-induced inflammation. The promising effect of CCE may be attributed to its high levels of polyphenols and fatty acid components. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lavandula angustifolia Mill. Essential Oil Exerts Antibacterial and Anti-Inflammatory Effect in Macrophage Mediated Immune Response to Staphylococcus aureus.

PubMed

Giovannini, D; Gismondi, A; Basso, A; Canuti, L; Braglia, R; Canini, A; Mariani, F; Cappelli, G

2016-01-01

Different studies described the antibacterial properties of Lavandula angustifolia (Mill.) essential oil and its anti-inflammatory effects. Besides, no data exist on its ability to activate human macrophages during the innate response against Staphylococcus aureus. The discovery of promising regulators of macrophage-mediated inflammatory response, without side effects, could be useful for the prevention of, or as therapeutic remedy for, various inflammation-mediated diseases. This study investigated, by transcriptional analysis, how a L. angustifolia essential oil treatment influences the macrophage response to Staphylococcus aureus infection. The results showed that the treatment increases the phagocytic rate and stimulates the containment of intracellular bacterial replication by macrophages. Our data showed that this stimulation is coupled with expression of genes involved in reactive oxygen species production (i.e., CYBB and NCF4). Moreover, the essential oil treatment balanced the inflammatory signaling induced by S. aureus by repressing the principal pro-inflammatory cytokines and their receptors and inducing the heme oxygenase-1 gene transcription. These data showed that the L. angustifolia essential oil can stimulate the human innate macrophage response to a bacterium which is responsible for one of the most important nosocomial infection and might suggest the potential development of this plant extract as an anti-inflammatory and immune regulatory coadjutant drug.

α-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease.

PubMed

Reifen, Ram; Karlinsky, Anna; Stark, Aliza H; Berkovich, Zipi; Nyska, Abraham

2015-12-01

Studies suggest that consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) plays a protective role in inflammatory bowel disease; however, the use of plant-derived oils rich in α-linolenic acid (ALA) has not been widely investigated. The aims of this study were to test the effects of two different sources of (n-3) PUFA, fish and plant-derived oils, in two animal models of experimental colitis and to determine whether the (n-3) PUFA-enriched diets could ameliorate the inflammatory status. Rats were fed diets rich in corn, fish or sage oil with or without vitamin A supplementation for 3weeks then colitis was induced by adding dextran sodium sulfate to the drinking water or by injecting 2,4,6-trinitrobenzene sulfonic acid. We show that colitic rats fed the sage oil diets had a lower inflammatory response, improved histological repair and had less necrotic damage in the mucosa when compared to the corn and fish oil groups. Colonic damage and myeloperoxidase activity were significantly lower. Colonic mRNA levels of pro-inflammatory genes including interleukin IL-6, cyclooxygenase 2 and tumor necrosis factor α were markedly down-regulated in rats fed fish and sage oils compared to control. These results were supported by experiments in the human colonic epithelial cell line Caco-2, where ALA supplementation was shown to be effective in inhibiting inflammation induced by IL-1β by down-regulating mRNA levels of pro-inflammatory genes including IL-8, COX2 and inducible nitric oxide synthase. Taken together, these results suggest that plant-derived oil rich in ALA could ameliorate the inflammatory damage in colitis. Copyright © 2015 Elsevier Inc. All rights reserved.

Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats.

PubMed

Arigesavan, Kaninathan; Sudhandiran, Ganapasam

2015-05-29

Chronic inflammation is one of the remarkable etiologic factors for various human ailments including cancer. The well known hypothesis is that persistent inflammation in colon can increase the risk of colorectal cancer (CRC). In this study, a pharmacological evaluation of carvacrol, a phenolic monoterpene constituent of essential oils produced from aromatic plant Oreganum vulgarea sp. on colitis associated colon cancer (CACC) induced by 1,2 Dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in male Fischer 344 rat model was studied. F344 rats were given three subcutaneous injections of DMH (40 mg/kg body wt) in the first week and were given free access to drinking water containing 1% DSS for the next one week followed by 7-14 days of water as three cycles. Carvacrol was administrated before and after tumor induction at a concentration of 50 mg/kg body weight (o.p). Carvacrol treated groups promotes the endogenous antioxidant system and suppress the inflammation in DMH/DSS induced animals. An increased antioxidant status and restoration of histological lesions in the inflamed colonic mucosa was observed in carvacrol treated rats. This effect was confirmed biochemically by reducing free-radical accumulation and suppressing expression of pro-inflammatory mediators. In this study, Carvacrol significantly increased the anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) levels and reduced lipid peroxides (LPO), myeloperoxidase (MPO) and nitric oxide (NO) as compared to DMH/DSS induced rats. These dramatic changes facilitate the suppression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β) in CACC induced rats. Taken together, these findings suggest that Carvacrol may play a beneficial role in DMH/DSS induced experimental rat model and serve as an excellent dietary antioxidant as well as anti-inflammatory agent. It may represent novel therapeutic interventions against colon cancer triggered by chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer.

PubMed

Rehman, Khurram; Zulfakar, Mohd Hanif

2017-01-01

To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis. Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model. Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer. Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

Nanovesicular carrier-based formulation for skin cancer targeting: evaluation of cytotoxicity, intracellular uptake, and preclinical anticancer activity.

PubMed

Jain, Subheet Kumar; Puri, Richa; Mahajan, Mohit; Yadav, Subodh; Pathak, C M; Ganesh, N

2015-04-01

Skin cancer has turned into global epidemic leading to higher incidences among cancer stricken population. The aim of the present investigation is to evaluate the anticancer potential and intracellular uptake of a novel nanovesicular formulation of 5-FU. Detailed intracellular uptake study in conjunction with estimation of intracellular reactive oxygen species was done using skin melanoma cell lines (A375) along with cytotoxicity studies. To further obtain the mechanistic insights into inhibition of tumor cell proliferation, cell-cycle arrest studies were conducted. The preclinical anticancer activity was carried out employing in vivo DMBA-croton oil-induced skin cancer model in mice. Significant reduction in the number of papillomas was observed in skin cancer-bearing mice on treatment with nanovesicular formulation (51.4 ± 3.2%) in comparison with marketed formulation (21.3 ± 2.1%) of 5-FU. Tumor volume was found to be reduced to 46.3 ± 3.5% with prepared formulation, whereas the marketed formulation-treated group showed the reduction of 18.6 ± 1.8% in comparison with the control (untreated) group. The results of present study demonstrated that nanovesicular formulation of 5-FU possessed the enhanced anticancer activity which could be attributed to better intracellular uptake, cellular retention, and sustained release of drug.

Direct Production of Propene from the Thermolysis of Poly(β-hydroxybutyrate) (PHB). An Experimental and DFT Investigation.

PubMed

Clark, Jared M; Pilath, Heidi M; Mittal, Ashutosh; Michener, William E; Robichaud, David J; Johnson, David K

2016-01-28

We demonstrate a synthetic route toward the production of propene directly from poly(β-hydroxybutyrate) (PHB), the most common of a wide range of high-molecular-mass microbial polyhydroxyalkanoates. Propene, a major commercial hydrocarbon, was obtained from the depolymerization of PHB and subsequent decarboxylation of the crotonic acid monomer in good yields (up to 75 mol %). The energetics of PHB depolymerization and the gas-phase decarboxylation of crotonic acid were also studied using density functional theory (DFT). The average activation energy for the cleavage of the R'C(O)O-R linkage is calculated to be 163.9 ± 7.0 kJ mol(-1). Intramolecular, autoacceleration effects regarding the depolymerization of PHB, as suggested in some literature accounts, arising from the formation of crotonyl and carboxyl functional groups in the products could not be confirmed by the results of DFT and microkinetic modeling. DFT results, however, suggest that intermolecular catalysis involving terminal carboxyl groups may accelerate PHB depolymerization. Activation energies for this process were estimated to be about 20 kJ mol(-1) lower than that for the noncatalyzed ester cleavage, 144.3 ± 6.4 kJ mol(-1). DFT calculations predict the decarboxylation of crotonic acid to follow second-order kinetics with an activation energy of 147.5 ± 6.3 kJ mol(-1), consistent with that measured experimentally, 146.9 kJ mol(-1). Microkinetic modeling of the PHB to propene overall reaction predicts decarboxylation of crotonic acid to be the rate-limiting step, consistent with experimental observations. The results also indicate that improvements made to enhance the isomerization of crotonic acid to vinylacetic acid will improve the direct conversion of PHB to propene.

Chondroprotective effects of a proanthocyanidin rich Amazonian genonutrient reflects direct inhibition of matrix metalloproteinases and upregulation of IGF-1 production by human chondrocytes

PubMed Central

Miller, Mark JS; Bobrowski, Paul; Shukla, Meenakshi; Gupta, Kalpana; Haqqi, Tariq M

2007-01-01

Background The Amazonian medicinal plant Sangre de grado (Croton palanostigma) has traditional applications for the treatment of wound healing and inflammation. We sought to characterize two extracts (progrado and zangrado) in terms of safety and oligomeric proanthocyanidin chain length. Additionally progrado was evaluated for antioxidant activity and possible chondroprotective actions. Methods Acute oral safety and toxicity was tested in rats according under OECD protocol number 420. The profile of proanthocyanidin oligomers was determined by HPLC and progrado's antioxidant activity quantified by the ORAC, NORAC and HORAC assays. Human cartilage explants, obtained from surgical specimens, were used to assess chondroproteciton with activity related to direct inhibitory effects on human matrix metalloproteinase (MMP, gelatinolytic) activity using synovial fluid and chondrocytes activated with IL-1β (10 ng/ml). Additionally, progrado (2–10 μg/ml) was tested for its ability to maintain optimal IGF-1 transcription and translation in cartilage explants and cultured chondrocytes. Results Both progrado and zangrado at doses up to 2000 mg/kg (po) displayed no evidence of toxicity. Oligomeric proanthocyanidin content was high for both progrado (158 mg/kg) and zangrado (124 mg/kg), with zangrado almost entirely composed of short oligomers (<6 mer), whereas the majority of oligomers in progrado exceeded 10 mers. Progrado was a remarkably potent antioxidant in the standardized tests ORAC, NORAC and HORAC. Progrado was exceptionally effective in reducing both basal and IL-1β induced glycosaminoglycan release from human cartilage explants at concentrations that also directly blocked the gelatinolytic activity of MMP-2 and MMP-9. Progrado prevented IL-1β induced suppression of IGF-1 production from human cartilage explants as well as stimulating basal IGF-1 production (P < 0.05). Comparable changes in IGF-1 gene expression were noted in cultured human chondrocytes. Conclusion Progrado has a promising safety profile, significant chondroprotective and antioxidant actions, directly inhibits MMP activity and promotes the production of the cartilage repair factor, IGF-1. This suggests that progrado may offer therapeutic benefits in joint health, wound healing and inflammation. PMID:17697350

Anticholinesterase activity of endemic plant extracts from Soqotra.

PubMed

Bakthira, Hussein; Awadh Ali, Nasser A; Arnold, Norbert; Teichert, Axel; Wessjohann, Ludger

2011-01-01

A total of 30 chloroform and methanol extracts from the following endemic Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil, Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. & Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm), Oldenlandia pulvinata, Pulicaria diversifolia (Balf. and Pulicaria stephanocarpa Balf. were screened for their acetylcholinesterase inhibitory activity by using in vitro Ellman method at 50 and 200 µg/ml concentrations. Chloroform extracts of Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited inhibitory activities higher than 50 % at concentration of 200 µg. At a concentrations of 50 µg, the chloroform extract of Croton socotranus exhibited an inhibition of 40.6 %.

The Crotone Megalandslide, southern Italy: Architecture, timing and tectonic control.

PubMed

Zecchin, Massimo; Accaino, Flavio; Ceramicola, Silvia; Civile, Dario; Critelli, Salvatore; Da Lio, Cristina; Mangano, Giacomo; Prosser, Giacomo; Teatini, Pietro; Tosi, Luigi

2018-05-17

Large-scale submarine gravitational land movements involving even more than 1,000 m thick sedimentary successions are known as megalandslides. We prove the existence of large-scale gravitational phenomena off the Crotone Basin, a forearc basin located on the Ionian side of Calabria (southern Italy), by seismic, morpho-bathymetric and well data. Our study reveals that the Crotone Megalandslide started moving between Late Zanclean and Early Piacenzian and was triggered by a contractional tectonic event leading to the basin inversion. Seaward gliding of the megalandslide continued until roughly Late Gelasian, and then resumed since Middle Pleistocene with a modest rate. Interestingly, the onshore part of the basin does not show a gravity-driven deformation comparable to that observed in the marine area, and this peculiar evidence allows some speculations on the origin of the megalandslide.

Chemical composition analysis and in vitro biological activities of ten essential oils in human skin cells.

PubMed

Han, Xuesheng; Beaumont, Cody; Stevens, Nicole

2017-12-01

Research on the biological effects of essential oils on human skin cells is scarce. In the current study, we primarily explored the biological activities of 10 essential oils (nine single and one blend) in a pre-inflamed human dermal fibroblast system that simulated chronic inflammation. We measured levels of proteins critical for inflammation, immune responses, and tissue-remodeling processes. The nine single oils were distilled from Citrus bergamia (bergamot), Coriandrum sativum (cilantro), Pelargonium graveolens (geranium), Helichrysum italicum (helichrysum), Pogostemon cablin (patchouli), Citrus aurantium (petitgrain), Santalum album (sandalwood), Nardostachys jatamansi (spikenard), and Cananga odorata (ylang ylang). The essential oil blend (commercial name Immortelle) is composed of oils from frankincense, Hawaiian sandalwood, lavender, myrrh, helichrysum, and rose. All the studied oils were significantly anti-proliferative against these cells. Furthermore, bergamot, cilantro, and spikenard essential oils primarily inhibited protein molecules related to inflammation, immune responses, and tissue-remodeling processes, suggesting they have anti-inflammatory and wound healing properties. Helichrysum and ylang ylang essential oils, as well as Immortelle primarily inhibited tissue remodeling-related proteins, suggesting a wound healing property. The data are consistent with the results of existing studies examining these oils in other models and suggest that the studied oils may be promising therapeutic candidates. Further research into their biological mechanisms of action is recommended. The differential effects of these essential oils suggest that they exert activities by different mechanisms or pathways, warranting further investigation. The chemical composition of these oils was analyzed using gas chromatography-mass spectrometry.

Pequi fruit (Caryocar brasiliense Camb.) pulp oil reduces exercise-induced inflammatory markers and blood pressure of male and female runners.

PubMed

Miranda-Vilela, Ana L; Pereira, Luiz C S; Gonçalves, Carlos A; Grisolia, Cesar K

2009-12-01

The objective of this study was to investigate the anti-inflammatory properties of pequi (Caryocar brasiliense) fruit oil and its effects on the postprandial lipidemia and arterial blood pressure of male and female athletes. These athletes were evaluated after races in the same environment and under the same type, intensity, and length of weekly training conditions, both before and after ingestion of 400 mg pequi oil capsules for 14 days. Pequi fruit contains several antioxidants, and its oil has been associated with anti-inflammatory properties in other pequi species. Because the oil of pequi is mostly composed of oleic and palmitic fatty acids, the oil may alter the ratio of triglyceride to cholesterol in postprandial lipidemia. Epidemiologic studies suggest that an increased intake of monounsaturated fatty acids (such as oleic acid) is inversely related to blood pressure. Thus, we hypothesize that pequi oil could reduce exercise-induced inflammation and blood pressure, and modulate postprandial lipidemia in runners. To test this hypothesis, arterial blood pressures were checked before races; blood samples were taken after the races and submitted for analysis of leukocytes and platelets analysis, high-sensitivity C-reactive protein values, and postprandial lipids. Pequi oil resulted in anti-inflammatory effects and reduced the total cholesterol and low-density lipoprotein in the age group older than 45 years, mainly for men. The results showed a general trend for reduced arterial pressure, suggesting that pequi oil may have a hypotensive effect. However, this finding needs additional investigation. Thus, pequi oil, besides possessing many nutritional properties, may be a good candidate supplement for athletes.

Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models.

PubMed

Santin, José Roberto; Lemos, Marivane; Klein-Júnior, Luiz Carlos; Machado, Isabel Daufenback; Costa, Philipe; de Oliveira, Ana Paula; Tilia, Crislaine; de Souza, Juliana Paula; de Sousa, João Paulo Barreto; Bastos, Jairo Kenupp; de Andrade, Sérgio Faloni

2011-02-01

Syzygium aromaticum, a medicinal plant commonly known as clove, is used to treat toothache, respiratory disorders, inflammation, and gastrointestinal disorders. From the flower buds of S. aromaticum, it is possible to obtain an essential oil comprised of a mixture of aliphatic and cyclic volatile terpenes and phenylpropanoids, being eugenol as the main component. The aims of this study were: (1) to extract the essential oil of the flower buds of S. aromaticum, (2) to identify and quantify the main component of the essential oil, and (3) to evaluate its antiulcer activity using different animal models. Assays were performed using the following protocols in rats: indomethacin-induced and ethanol/HCl-induced ulcer model. Both essential oils from S. aromaticum and eugenol displayed antiulcer activities in the rat models of indomethacin- and ethanol-induced ulcer. Studies focusing on the possible mechanisms of gastroprotection were also undertaken using the following experiments: evaluation of gastric secretion by the pylorus-ligated model, determination of mucus in gastric content, participation of nitric oxide (NO) and endogenous sulfhydryl in gastric protection. The results show that there was no significant effect on the volume of gastric juice and total acidity. However, the quantification of free gastric mucus showed that the clove oil and eugenol were capable of significantly enhancing mucus production. With regard to the NO and endogenous sulfhydryls, the results demonstrated that the gastroprotection induced by clove oil and eugenol are not related to the activities of the nitric oxide and endogenous sulfhydryls. No sign of toxicity was observed in the acute toxicity study. In conclusion, the results of this study show that essential oil of S. aromaticum, as well as its main component (eugenol), possesses antiulcer activity. The data suggest that the effectiveness of the essential oil and eugenol is based on its ability to stimulate the synthesis of mucus, an important gastroprotective factor. However, further pharmacological and toxicological investigations are required to enable its use for the treatment of gastric ulcer.

Antimetastatic and Anti-Inflammatory Potentials of Essential Oil from Edible Ocimum sanctum Leaves

PubMed Central

Thirugnanasampandan, Ramaraj; Jayakumar, Rajarajeswaran; Ramya, Gunasekar; Ramnath, Gogul

2014-01-01

Antimetastatic and anti-inflammatory activities of Ocimum sanctum essential oil (OSEO) have been assessed in this study. OSEO at the concentration of 250 μg/mL and above showed a significant (* P < 0.05) decrease in the number of migrated cancer cells. In addition, OSEO at concentration of 250 μg/mL and above suppressed MMP-9 activity in lipopolysaccharide (LPS) induced inflammatory cells. A dose-dependent downregulation of MMP-9 expression was observed with the treatment of OSEO compared to the control. Our findings indicate that OSEO has both antimetastatic and anti-inflammatory potentials, advocating further investigation for clinical applications in the treatment of inflammation associated cancer. PMID:25431779

Fish Oil Contaminated with Persistent Organic Pollutants Reduces Antioxidant Capacity and Induces Oxidative Stress without Affecting Its Capacity to Lower Lipid Concentrations and Systemic Inflammation in Rats.

PubMed

Hong, Mee Young; Lumibao, Jan; Mistry, Prashila; Saleh, Rhonda; Hoh, Eunha

2015-05-01

Numerous studies have investigated the benefits of fish, fish oil, and ω-3 (n-3) polyunsaturated fatty acids against cardiovascular diseases. However, concern surrounding contamination with persistent organic pollutants (POPs) prompts caution in the recommendation to consume fish and fish oil. The present study compared the effects of fish oil contaminated with polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) on serum lipid profiles, inflammation, and oxidative stress. Twenty eight-day-old male Sprague-Dawley rats (n = 30) consumed diets of unmodified fish oil (FO) consisting of 15% fat by weight, persistent organic pollutant-contaminated fish oil (POP FO) (PCBs at 2.40 μg/g; OCs at 3.80 μg/g FO), or corn oil (control; CO) for 9 wk. Lipid profiles and C-reactive protein concentrations were assessed. Hepatic gene expression related to lipid metabolism was determined by real time quantitative polymerase chain reaction analysis. After 9 wk of feeding, accumulation of PCBs and OCs in the fat tissue of the POP FO group compared with the other 2 groups was confirmed (P < 0.01). Both fish oil groups showed greater HDL cholesterol (FO 53 ± 5.3 and POP FO 55 ± 7.7 vs. CO 34 ± 2.3 mg/dL), but lower triglycerides (24 ± 2.8 and 22 ± 3.0 vs. 43 ± 5.6 mg/dL), LDL cholesterol (38 ± 14 and 34 ± 9.2 vs. 67 ± 4.4 mg/dL), and C-reactive protein (113 ± 20 and 120 ± 26 vs. 189 ± 22 μg/dL) compared with the CO group (P < 0.05). Gene expression of fatty acid synthase in both fish oil groups was also less than in the CO group (P < 0.05). However, the POP FO group showed greater lipid peroxidation (5.1 ± 0.7 vs. 2.9 ± 0.9 and 2.6 ± 0.6 μM) and less antioxidant capacity (0.08 ± 0.06 vs. 0.5 ± 0.1 and 0.4 ± 0.1 mM) than the CO and FO groups (P < 0.05). These findings indicate that, despite exhibiting benefits on serum lipid concentrations and inflammation, contamination with PCBs and OCs showed significant negative effects on oxidative stress and antioxidant capacity in rats. Future studies should investigate the effects of different contaminant doses and the possibility of a dose-dependent response, a lengthened feeding time, and interactions between contaminant mixtures and oils of varying composition to advise on dietary consumption of fish and fish oil. © 2015 American Society for Nutrition.

GENETIC DIFFERENCES IN IN VIVO/IN VITRO AIRWAY INJURY AND INFLAMMATION AFTER OIL FLY ASH EXPOSURE

EPA Science Inventory

GENETIC DIFFERENCES IN IN VIVO/ IN VITRO AIRWAY INJURY/ INFLAMMATION AFTER OIL FLY ASH EXPOSURE

Janice Dye, Debora Andrews, Judy Richards, Annette King*, Urmila Kodavanti. US EPA & *SEE Program, RTP, NC.

Oxidative stress is implicated in the pathogenesis and progres...

Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice

USDA-ARS?s Scientific Manuscript database

The effects of fish oil supplements on diminishing airway inflammation in asthma have been studied in mouse models and human intervention trials with varying results. However, the independent effects of the main omega-3 PUFAs found in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (D...

Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflammation in vitro and in vivo.

PubMed

Hong, Yong-Han; Chao, Wen-Wan; Chen, Miaw-Ling; Lin, Bi-Fong

2009-07-14

This study aimed to investigate if food components that exert anti-inflammatory effects may be used for inflammatory disorders by examining alfalfa sprout ethyl acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with acute inflammation after intra-peritoneal (ip) injection of 15 mg/kg BW lipopolysaccharide (LPS) were determined. The results showed that the life span of LPS-induced inflammatory mice were negatively correlated with serum levels of TNF-alpha, IL-6, and IL-1beta at 9 hr after LPS-injection, which indicated that suppressing these cytokines in the late phase of inflammation may be beneficial for survival. The in vitro experiment then showed that ASEA significantly reduced IL-6 and IL-1beta production and the NF-kappaB trans-activation activity of mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory effects of ASEA in vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in 50 microl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 50 microl sunflower oil/day only. After one week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS. The results showed that the ASEA and PDTC groups had significantly lower serum TNF-alpha, IL-6, and IL-1beta levels at 9 hr after LPS challenge, and significantly higher survival rates than the control group. This study suggests that ASEA supplementation can suppress the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards.

Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflammation in vitro and in vivo

PubMed Central

Hong, Yong-Han; Chao, Wen-Wan; Chen, Miaw-Ling; Lin, Bi-Fong

2009-01-01

This study aimed to investigate if food components that exert anti-inflammatory effects may be used for inflammatory disorders by examining alfalfa sprout ethyl acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with acute inflammation after intra-peritoneal (ip) injection of 15 mg/kg BW lipopolysaccharide (LPS) were determined. The results showed that the life span of LPS-induced inflammatory mice were negatively correlated with serum levels of TNF-α, IL-6, and IL-1β at 9 hr after LPS-injection, which indicated that suppressing these cytokines in the late phase of inflammation may be beneficial for survival. The in vitro experiment then showed that ASEA significantly reduced IL-6 and IL-1β production and the NF-κB trans-activation activity of mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory effects of ASEA in vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in 50 μl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 50 μl sunflower oil/day only. After one week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS. The results showed that the ASEA and PDTC groups had significantly lower serum TNF-α, IL-6, and IL-1β levels at 9 hr after LPS challenge, and significantly higher survival rates than the control group. This study suggests that ASEA supplementation can suppress the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards. PMID:19594948

Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils.

PubMed

Özek, Gulmira; Schepetkin, Igor A; Utegenova, Gulzhakhan A; Kirpotina, Liliya N; Andrei, Spencer R; Özek, Temel; Başer, Kemal Hüsnü Can; Abidkulova, Karime T; Kushnarenko, Svetlana V; Khlebnikov, Andrei I; Damron, Derek S; Quinn, Mark T

2017-06-01

Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were ( E )-propenyl sec -butyl disulfide (15.7-39.4%) and ( Z )-propenyl sec -butyl disulfide (23.4-45.0%). Ferula essential oils stimulated [Ca 2+ ] i mobilization in human neutrophils and activated ROS production in human neutrophils and murine bone marrow phagocytes. Activation of human neutrophil [Ca 2+ ] i flux by Ferula essential oils was dose-dependently inhibited by capsazepine, a TRPV1 channel antagonist, indicating that TRPV1 channels mediate this response. Furthermore, Ferula essential oils stimulated Ca 2+ influx in TRPV1 channel-transfected HEK293 cells and desensitized the capsaicin-induced response in these cells. Additional molecular modeling with known TRPV1 channel agonists suggested that the active component is likely to be ( Z )-propenyl sec -butyl disulfide. Our results provide a cellular and molecular basis to explain at least part of the beneficial therapeutic properties of FEOs. © Society for Leukocyte Biology.

c9t11-Conjugated linoleic acid-rich oil fails to attenuate wasting in colon-26 tumor-induced late-stage cancer cachexia in male CD2F1 mice.

PubMed

Tian, Min; Kliewer, Kara L; Asp, Michelle L; Stout, Michael B; Belury, Martha A

2011-02-01

Cancer cachexia is characterized by muscle and adipose tissue wasting caused partly by chronic, systemic inflammation. Conjugated linoleic acids (CLAs) are a group of fatty acids with various properties including anti-inflammatory cis9, trans11 (c9t11)-CLA and lipid-mobilizing trans10, cis12 (t10c12)-CLA. The purpose of this study was to test whether dietary supplementation of a c9t11-CLA-rich oil (6:1 c9t11:t10c12) could attenuate wasting of muscle and adipose tissue in colon-26 adenocarcinoma-induced cachexia in mice. Loss of body weight, muscle and adipose tissue mass caused by tumors were not rescued by supplementation with the c9t11-CLA-rich oil. In quadriceps muscle, c9t11-CLA-rich oil exacerbated tumor-induced gene expression of inflammatory markers tumor necrosis factor-α, IL-6 receptor and the E3 ligase MuRF-1 involved in muscle proteolysis. In epididymal adipose tissue, tumor-driven delipidation and atrophy was aggravated by the c9,t11-CLA-rich oil, demonstrated by further reduced adipocyte size and lower adiponectin expression. However, expression of inflammatory cytokines and macrophage markers were not altered by tumors, or CLA supplementation. These data suggest that addition of c9t11-CLA-rich oil (0.6% c9t11, 0.1% t10c12) in diet did not ameliorate wasting in mice with cancer cachexia. Instead, it increased expression of inflammatory markers in the muscle and increased adipose delipidation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Participation of citral in the bronchodilatory effect of ginger oil and possible mechanism of action.

PubMed

Mangprayool, Thitiya; Kupittayanant, Sajeera; Chudapongse, Nuannoi

2013-09-01

The extract of ginger, the rhizomes of Zingiber officinale Roscoe (Zingiberaceae), has been reported to possess anti-hyperactivity and anti-inflammation on airway. The present study described brochodilatory activity of ginger oil and identified its active compound. Ginger oil was extracted by hydro-distillation. The compositions of ginger oil were analyzed by gas chromatography and mass spectrometer. Citral, eucalyptol and camphene were found to be the major components. Ginger oil and citral, but not camphene, suppressed rat tracheal contraction induced by carbachol (CCh). Consistent with previous report, eucalyptol showed a relaxing effect on rat airway. Since the content of eucalyptol in ginger oil was relatively low, the contribution of eucalyptol to the bronchodilatory effect of ginger oil was small. To elucidate the mechanisms responsible for the myorelaxing effect, propranolol (a β-adrenergic receptor antagonist), indomethacin (a COX inhibitor) and L-NAME (a NOS inhibitor) were used to block the inhibitory effects of ginger oil and citral. It was found that propranolol, but not indomethacin and L-NAME, reversed bronchodilatory effects of both ginger oil and citral, suggesting that a possible mechanism involved β-adrenergic receptor. This study provides the pharmacological basis supporting the therapeutic potential of Z. officinale rhizomes as a bronchodilator. Copyright © 2013 Elsevier B.V. All rights reserved.

Anti-atherosclerotic and anti-inflammatory actions of sesame oil.

PubMed

Narasimhulu, Chandrakala Aluganti; Selvarajan, Krithika; Litvinov, Dmitry; Parthasarathy, Sampath

2015-01-01

Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Nonpharmacological means of treating chronic diseases have gained attention recently. We previously reported that sesame oil has anti-atherosclerotic properties. In this study, we have determined the mechanisms by which sesame oil might modulate atherosclerosis by identifying genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR(-/-)) female mice were fed with either an atherogenic diet or an atherogenic diet reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for cytokine analysis. RNA was extracted from the liver tissue and used for global gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions, plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR(-/-) mice. Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1α, IL-6, and CXCL-16, were significantly reduced, demonstrating an anti-inflammatory property of sesame oil. Gene array analysis showed that sesame oil induced many genes, including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol metabolism and reverse cholesterol transport. In conclusion, our studies suggest that a sesame oil-enriched diet could be an effective nonpharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

Composition and cytotoxic and antioxidant activities of the oil of Piper aequale Vahl.

PubMed

da Silva, Joyce Kelly R; Pinto, Laine C; Burbano, Rommel M R; Montenegro, Raquel C; Andrade, Eloísa Helena A; Maia, José Guilherme S

2016-10-07

Piper aequale Vahl is a small shrub that grows in the shadow of large trees in the Carajás National Forest, Municipality of Parauapebas, Para state, Brazil. The local people have used the plant against rheumatism and inflammation. The essential oil of the aerial parts was extracted and analyzed by GC and GC-MS. The MTT colorimetric assay was used to measuring the cytotoxic activity of the oil against human cancer lines. The determination of antioxidant activity of the oil was conducted by DPPH radical scavenging assay. The main constituents were δ-elemene (18.92 %), β-pinene (15.56 %), α-pinene (12.57 %), cubebol (7.20 %), β-atlantol (5.87 %), and bicyclogermacrene (5.51 %), totalizing 65.63 % of the oil. The oil displayed a strong in vitro cytotoxic activity against the human cancer cell lines HCT-116 (colon) and ACP03 (gastric) with IC 50 values of 8.69 μg/ml and 1.54 μg/ml, respectively. The oil has induced the apoptosis in a gastric cancer cells in all tested concentration (0.75-3.0 μg/ml), after 72 h of treatment, when compared to negative control (p < 0.001). Also, the oil showed a significant antioxidant activity (280.9 ± 22.2 mg TE/ml), when analyzed as Trolox equivalent, and a weak acetylcholinesterase inhibition, with a detection limit of 100 ng, when compared to the physostigmine standard (1.0 ng). The higher cell growth inhibition induced by the oil of P. aequale is probably due to its primary terpene compounds, which were previously reported in the proliferation inhibition, in stimulation of apoptosis and induction of cell cycle arrest in malignant cells.

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.

PubMed

Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

2012-06-01

Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss.

Antinociceptive effects, acute toxicity and chemical composition of Vitex agnus-castus essential oil.

PubMed

Khalilzadeh, Emad; Vafaei Saiah, Gholamreza; Hasannejad, Hamideh; Ghaderi, Adel; Ghaderi, Shahla; Hamidian, Gholamreza; Mahmoudi, Razzagh; Eshgi, Davoud; Zangisheh, Mahsa

2015-01-01

Vitex agnus-castus (VAC) and its essential oil have been traditionally used to treat many conditions and symptoms such as premenstrual problems, mastalgia, inflammation, sexual dysfunction, and pain. In this study, the effects of essential oil extracted from Vitex agnus-castus (EOVAC) leaves were investigated in three behavioral models of nociception in adult male Wistar rats. Chemical composition of EOVAC was analyzed using gas chromatography - mass spectrometry (GC-MS) and also its possible toxicity was determined in mice. Analgesic effect of EOVAC was determined using tail immersion test, formalin test, and acetic acid-induced visceral pain in rats. EOVAC (s.c.) and morphine (i.p.) significantly (p<0.05) reduced pain responses in both formalin and tail immersion tests. In the study of evolved mechanisms, pretreatment with naloxone or atropine significantly (p <0.05) reversed the essential oil-induced analgesia in both formalin and tail immersion tests. Moreover, EOVAC and Piroxicam produced significant (p<0.05) inhibition in the acetic acid-induced writhing response. EOVAC did not show any mortality even at high dose (5 g/kg, p.o.) of administration in toxicity test. Moreover, according to GC-MS results, major components of the EOVAC were α-pinene (14.83%), limonene (10.29%), β-caryophyllene (6.9%), sabinene (5.27%), and β-farnesene (5.9%). These results suggest that endogenous opioidergic system as well as muscarinergic receptors of cholinergic system may be involve in the antinociceptive activity of Vitex agnus-castus essential oil in these models of pain in rats.

Antinociceptive effects, acute toxicity and chemical composition of Vitex agnus-castus essential oil

PubMed Central

Khalilzadeh, Emad; Vafaei Saiah, Gholamreza; Hasannejad, Hamideh; Ghaderi, Adel; Ghaderi, Shahla; Hamidian, Gholamreza; Mahmoudi, Razzagh; Eshgi, Davoud; Zangisheh, Mahsa

2015-01-01

Objective: Vitex agnus-castus (VAC) and its essential oil have been traditionally used to treat many conditions and symptoms such as premenstrual problems, mastalgia, inflammation, sexual dysfunction, and pain. In this study, the effects of essential oil extracted from Vitex agnus-castus (EOVAC) leaves were investigated in three behavioral models of nociception in adult male Wistar rats. Materials and methods: Chemical composition of EOVAC was analyzed using gas chromatography – mass spectrometry (GC-MS) and also its possible toxicity was determined in mice. Analgesic effect of EOVAC was determined using tail immersion test, formalin test, and acetic acid-induced visceral pain in rats. Results: EOVAC (s.c.) and morphine (i.p.) significantly (p<0.05) reduced pain responses in both formalin and tail immersion tests. In the study of evolved mechanisms, pretreatment with naloxone or atropine significantly (p <0.05) reversed the essential oil-induced analgesia in both formalin and tail immersion tests. Moreover, EOVAC and Piroxicam produced significant (p<0.05) inhibition in the acetic acid-induced writhing response. EOVAC did not show any mortality even at high dose (5 g/kg, p.o.) of administration in toxicity test. Moreover, according to GC-MS results, major components of the EOVAC were α-pinene (14.83%), limonene (10.29%), β-caryophyllene (6.9%), sabinene (5.27%), and β-farnesene (5.9%). Conclusions: These results suggest that endogenous opioidergic system as well as muscarinergic receptors of cholinergic system may be involve in the antinociceptive activity of Vitex agnus-castus essential oil in these models of pain in rats. PMID:26101755

Cocoa butter and safflower oil elicit different effects on hepatic gene expression and lipid metabolism in rats.

PubMed

Gustavsson, Carolina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

2009-11-01

The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for 3 days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic beta-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by 3 days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavorable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet.

Seasonal Variability and Effects of Stormflow on Concentrations of Pesticides and their Degradates in Kisco River and Middle Branch Croton River Surface Water, Croton Reservoir System, New York, May 2000-February 2001

USGS Publications Warehouse

Phillips, Patrick J.; Bode, Robert W.

2004-01-01

Seven herbicides (2,4-D, 2,4-D methyl ester, bromacil, dicamba, diuron, imazaquin, and sulfometuron), four insecticides (carbaryl, diazinon, imidacloprid, and malathion), two fungicides (metalaxyl and myclobutanil), and caffeine (an indicator of wastewater) were detected in at least one sample from the Kisco River at concentrations above 0.1 ug/L (micrograms per liter). Four of these compounds - 2,4-D, 2,4-D methyl ester, dicamba, and metalaxyl - were detected in at least one sample from the Kisco River at a concentration above 1 ug/L. Only three herbicides (2,4-D, imazethapyr, and prometon) and caffeine were detected at concentrations above 0.1 ug/L in one or more of the Middle Branch Croton River samples, and no compounds were detected above 0.4 ug/L in Middle Branch Croton River samples. No samples contained concentrations of pesticides that exceeded human health-based water-quality standards. However, samples from the Kisco River contained four insecticides (carbaryl, chlorpyrifos, diazinon, and malathion) and one herbicide (2,4-D) in concentrations that exceeded water-quality criteria for the protection of aquatic life. Aquatic-life protection criteria were generally exceeded only in stormflow samples collected in June, September, and December 2000. No samples from the Middle Branch Croton River contained target compounds that exceeded water-quality criteria for the protection of aquatic life. Pesticide concentrations were generally higher, and the numbers of compounds generally larger in samples from the Kisco River than in samples from the Middle Branch Croton River, probably because the Kisco River watershed has a greater population density and is more extensively developed. The highest concentrations of most compounds in both streams were detected in stormflow samples collected in June, September, and December 2000. This indicates that stormflow sampling is essential in assessments of pesticide occurrence in streams that drain developed lands. The lowest concentrations of most compounds at both sites were detected in baseflow samples collected from October 2000 through February 2001, although the concentrations of several compounds increased substantially during stormflows at the Kisco River site in November and December, 2000.

Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway.

PubMed

Lu, Xue-Li; Zhao, Cui-Hua; Yao, Xin-Liang; Zhang, Han

2017-01-01

Quercetin is a dietary flavonoid compound extracted from various plants, such as apple and onions. Previous studies have revealed its anti-inflammatory, anti-cancer, antioxidant and anti-apoptotic activities. This study investigated the ability of quercetin to inhibit high fructose feeding- or LPS-induced atherosclerosis through regulating oxidative stress, apoptosis and inflammation response in vivo and in vitro experiments. 50 and 100mg/kg quercetin were used in our study, showing significant inhibitory role in high fructose-induced atherosclerosis via reducing reactive oxygen species (ROS) levels, Caspase-3 activation, inflammatory cytokines releasing, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and collagen contents as well as modulating apoptosis- and inflammation-related proteins expression. We also explored the protective effects of quercetin on atherosclerosis by phosphatidylinositide 3-kinases (PI3K)/Protein kinase B (AKT)-associated Bcl-2/Caspase-3 and nuclear factor kappa B (NF-κB) signal pathways activation, promoting AKT and Bcl-2 expression and reducing Caspase-3 and NF-κB activation. Quercetin reduced the atherosclerotic plaque size in vivo in high fructose feeding-induced mice assessed by oil red O. Also, in vitro experiments, quercetin displayed inhibitory role in LPS-induced ROS production, inflammatory response and apoptosis, which were linked with PI3K/AKT-regulated Caspase-3 and NF-κB activation. In conclusion, our results showed that quercetin inhibited atherosclerotic plaque development in high fructose feeding mice via PI3K/AKT activation regulated by ROS. Copyright © 2016. Published by Elsevier Masson SAS.

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

PubMed

Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

2013-01-01

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. © 2013 Published by Elsevier Ltd.

The Essential Oils of Rhaponticum carthamoides Hairy Roots and Roots of Soil-Grown Plants: Chemical Composition and Antimicrobial, Anti-Inflammatory, and Antioxidant Activities.

PubMed

Skała, Ewa; Rijo, Patrícia; Garcia, Catarina; Sitarek, Przemysław; Kalemba, Danuta; Toma, Monika; Szemraj, Janusz; Pytel, Dariusz; Wysokińska, Halina; Śliwiński, Tomasz

2016-01-01

The essential oils were isolated by hydrodistillation from the hairy roots (HR) and roots of soil-grown plants (SGR) of Rhaponticum carthamoides and were analyzed by GC-MS method. In the both essential oils 62 compounds were identified. The root essential oils showed the differences in the qualitative and quantitative composition. The sesquiterpene hydrocarbons (55-62%) dominated in both essential oils. The major compounds of HR essential oil were cyperene, 13-norcypera-1(5),11(12)-diene, and cadalene while aplotaxene, nardosina-1(10),11-diene, and dauca-4(11),8-diene dominated in SGR essential oil. Both essential oils showed antibacterial activity especially against Enterococcus faecalis (ATCC 29212) and Pseudomonas aeruginosa (ATCC 27853) (MIC value = 125  µ g/mL). HR and SGR essential oils also decreased the expression of IL-1 β , IL-6, and TNF- α and the ROS level in LPS-treatment astrocytes. This is the first report to describe the chemical composition of R. carthamoides essential oil from hairy roots, its protective effect against LPS-induced inflammation and ROS production in astrocytes, and its antimicrobial potential. The results show that R. carthamoides hairy roots may be a valuable source of the essential oil and may be an alternative to the roots of soil-grown plants.

The Essential Oils of Rhaponticum carthamoides Hairy Roots and Roots of Soil-Grown Plants: Chemical Composition and Antimicrobial, Anti-Inflammatory, and Antioxidant Activities

PubMed Central

Rijo, Patrícia; Garcia, Catarina; Kalemba, Danuta; Toma, Monika; Szemraj, Janusz; Pytel, Dariusz; Śliwiński, Tomasz

2016-01-01

The essential oils were isolated by hydrodistillation from the hairy roots (HR) and roots of soil-grown plants (SGR) of Rhaponticum carthamoides and were analyzed by GC-MS method. In the both essential oils 62 compounds were identified. The root essential oils showed the differences in the qualitative and quantitative composition. The sesquiterpene hydrocarbons (55–62%) dominated in both essential oils. The major compounds of HR essential oil were cyperene, 13-norcypera-1(5),11(12)-diene, and cadalene while aplotaxene, nardosina-1(10),11-diene, and dauca-4(11),8-diene dominated in SGR essential oil. Both essential oils showed antibacterial activity especially against Enterococcus faecalis (ATCC 29212) and Pseudomonas aeruginosa (ATCC 27853) (MIC value = 125 µg/mL). HR and SGR essential oils also decreased the expression of IL-1β, IL-6, and TNF-α and the ROS level in LPS-treatment astrocytes. This is the first report to describe the chemical composition of R. carthamoides essential oil from hairy roots, its protective effect against LPS-induced inflammation and ROS production in astrocytes, and its antimicrobial potential. The results show that R. carthamoides hairy roots may be a valuable source of the essential oil and may be an alternative to the roots of soil-grown plants. PMID:28074117

Modified immunoglobulin G glycosylation pattern during turpentine-induced acute inflammation in rats.

PubMed

Canellada, Andrea; Margni, Ricardo A

2002-01-01

Alterations in the pattern of protein glycosylation have been described during inflammation. In chronic parasitic and tumoral diseases we have reported an increase in the proportion of serum Immunoglobulin G (IgG) molecules possessing an altered Fab glycosylation pattern designated asymmetric antibodies. The alteration results in augmented concanavalin A affinity and functional univalence of the antibody. In addition, Fc agalactosylation has been described as occurring in chronically autoimmune diseases. Therefore, the aim of this paper was to evaluate by analyzing sera whether during an acute inflammatory response in rats produced by subcutaneous inoculation of turpentine oil, there was an alteration in the synthesis and glycosylation of IgG (as revealed by concanavalin A binding). We found that during acute inflammation there was a decrease in the synthesis of IgG which was not affected by prior oral administration of dexamethasone; however, the turpentine-induced increase in IgG binding to concanavalin A was found to be inhibited upon prior administration of the anti-inflammatory agent. As with turpentine, the corticoid used induced an increase in the interleukin-6 levels detected in sera by ELISA. Although we have described an improvement in asymmetric antibody synthesis by low dose of interleukin-6 previously, here we found no correlation between the observed glycosylation pattern of IgG and interleukin-6 concentration assessed in sera of treated rats, probably due to a different dexamethasone mediated pathway.

Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice

PubMed Central

Sheweita, Salah A.; El-Hosseiny, Lobna S.; Nashashibi, Munther A.

2016-01-01

Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn’t change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared to control group. In addition, treatment of mice with CP was found to induce the protein expression of CYP 3A4, 2B1/2, 2C6, 2C23. Moreover, the present study showed that essential oils reduced the expression of CYPs 2E1, 3A4 but could not restore the expression of CYP 2C6 and 2C23 compared to CP-treated mice. Interestingly, pretreatment of mice with essential oil of clove was found to restore activities of DMN-dI, AHH, and ECOD which were induced by CP to their normal control levels. It is concluded that EOs showed a marked hepatoprotective effect against hepatotoxicity induced by CP. In addition, co-administration of CP with any of these oils might be used as a new strategy for cancer treatment to alleviate the hepatotoxicity induced by CP. PMID:27802299

Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice.

PubMed

Sheweita, Salah A; El-Hosseiny, Lobna S; Nashashibi, Munther A

2016-01-01

Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn't change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared to control group. In addition, treatment of mice with CP was found to induce the protein expression of CYP 3A4, 2B1/2, 2C6, 2C23. Moreover, the present study showed that essential oils reduced the expression of CYPs 2E1, 3A4 but could not restore the expression of CYP 2C6 and 2C23 compared to CP-treated mice. Interestingly, pretreatment of mice with essential oil of clove was found to restore activities of DMN-dI, AHH, and ECOD which were induced by CP to their normal control levels. It is concluded that EOs showed a marked hepatoprotective effect against hepatotoxicity induced by CP. In addition, co-administration of CP with any of these oils might be used as a new strategy for cancer treatment to alleviate the hepatotoxicity induced by CP.

Protective activity of geranium oil and its component, geraniol, in combination with vaginal washing against vaginal candidiasis in mice.

PubMed

Maruyama, Naho; Takizawa, Toshio; Ishibashi, Hiroko; Hisajima, Tatsuya; Inouye, Shigeharu; Yamaguchi, Hideyo; Abe, Shigeru

2008-08-01

In order to evaluate an effective administration method of essential oils for vaginal candidiasis, efficacy of vaginal application of essential oils against murine experimental candidiasis was investigated. The effect on vaginal inflammation and Candida growth form was also studied. Vaginal candidiasis was established by intravaginal infection of C. albicans to estradiol-treated mice. These mice intravaginally received essential oils such as geranium and tea tree singly or in combination with vaginal washing. Vaginal administration of clotrimazole significantly decreased the number of viable C. albicans cells in the vaginal cavity by itself. In contrast, these essential oils did not lower the cell number. When application of geranium oil or geraniol was combined with vaginal washing, the cell number was decreased significantly. The myeloperoxidase activity assay exhibited the possibility that essential oils worked not only to reduce the viable cell number of C. albicans, but also to improve vaginal inflammation. The smear of vaginal washing suspension suggested that more yeast-form cells appeared in vaginal smears of these oil-treated mice than in control mice. In vitro study showed that a very low concentration (25 microg/ml) of geranium oil and geraniol inhibited mycelial growth, but not yeast growth. Based on these findings, it is estimated that vaginal application of geranium oil or its main component, geraniol, suppressed Candida cell growth in the vagina and its local inflammation when combined with vaginal washing.

Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men.

PubMed

Jiménez-Gómez, Yolanda; López-Miranda, José; Blanco-Colio, Luis M; Marín, Carmen; Pérez-Martínez, Pablo; Ruano, Juan; Paniagua, Juan A; Rodríguez, Fernando; Egido, Jesús; Pérez-Jiménez, Francisco

2009-06-01

Inflammation is crucial in all stages of atherosclerosis, and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postprandial period. To evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects. 20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA). The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.). Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts.

Fish oil concentrate delays sensitivity to thermal nociception in mice

PubMed Central

Veigas, Jyothi M.; Williams, Paul J.; Halade, Ganesh; Rahman, Mizanur M.; Yoneda, Toshiyuki; Fernandes, Gabriel

2011-01-01

Fish oil has been used to alleviate pain associated with inflammatory conditions such as rheumatoid arthritis. The anti-inflammatory property of fish oil is attributed to the n-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid. Contrarily, vegetable oils such as safflower oil are rich in n-6 fatty acids which are considered to be mediators of inflammation. This study investigates the effect of n-3 and n-6 fatty acids rich oils as dietary supplements on the thermally induced pain sensitivity in healthy mice. C57Bl/6J mice were fed diet containing regular fish oil, concentrated fish oil formulation (CFO) and safflower oil (SO) for 6 months. Pain sensitivity was measured by plantar test and was correlated to the expression of acid sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1) and c-fos in dorsal root ganglion cells. Significant delay in sensitivity to thermal nociception was observed in mice fed CFO compared to mice fed SO (p<0.05). A significant diminution in expression of ion channels such as ASIC1a (64%), ASIC13 (37%) and TRPV1 (56%) coupled with reduced expression of c-fos, a marker of neuronal activation, was observed in the dorsal root ganglion cells of mice fed CFO compared to that fed SO. In conclusion, we describe here the potential of fish oil supplement in reducing sensitivity to thermal nociception in normal mice. PMID:21345372

Short-term effects of scaling and root planing with or without adjunctive use of an essential-oil-based mouthwash in the treatment of periodontal inflammation in smokers.

PubMed

Alshehri, Mohammad; Alshail, Faisal; Alqahtani, Sami H; Aloriny, Tawfeeg Saleh; Alsharif, Abdulhakim; Kujan, Omar

2015-09-01

The aim of the present short-term follow-up study was to assess the effects of scaling and root planing (SRP) with or without adjunctive use of an essential-oil-based mouthwash in the treatment of periodontal inflammation in smokers. In total, 120 individuals were divided into 2 groups. In Group-1, 60 smokers with periodontal inflammation received SRP alone; and in Group-2, 60 smokers with periodontal inflammation received adjunct essential-oil mouthwash therapy. Periodontal parameters (plaque index [PI], bleeding-on-probing [BOP], and probing pocket depth [PD] ≥ 4 mm) were assessed at baseline and after 90 days of treatment. There was no significant difference in periodontal parameters (PI, BOP, and PD ≥ 4 mm) among participants in Group-1 and -2. Participants in both groups showed significant reductions in PI (P < 0.01), BOP (P < 0.01), and PD ≥ 4 mm (P < 0.01) at follow-up compared to baseline. At 90 days of follow-up, PI (P < 0.05), BOP (P < 0.05), and PD ≥ 4 mm (P < 0.05) were significantly higher in Group-1 compared to Group-2. SRP with adjunct essential-oil mouthwash therapy is more effective in the treatment of periodontal inflammation in smokers as compared to when SRP is performed alone.

Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex.

PubMed

Biscaro, Fernanda; Parisotto, Eduardo Benedetti; Zanette, Vanilde Citadini; Günther, Tania Mara Fischer; Ferreira, Eduardo Antonio; Gris, Eliana Fortes; Correia, João Francisco Gomes; Pich, Claus Tröger; Mattivi, Fulvio; Filho, Danilo Wilhelm; Pedrosa, Rozangela Curi

2013-06-01

Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragão". Its red latex is used traditionally for treating ulcers, diabetes and cancer. To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ± 1.84 and 1527.41 ± 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC50 = 169.0 ± 1.8 and 187.0 ± 2.2 μg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.

Antiviral and antiphlogistic activities of Hamamelis virginiana bark.

PubMed

Erdelmeier, C A; Cinatl, J; Rabenau, H; Doerr, H W; Biber, A; Koch, E

1996-06-01

A crude hydroalcoholic extract from Hamamelis virginiana bark was subjected to ultrafiltration (UF) with a cut-off limit of 3 kDa to obtain a higher and a lower molecular weight fraction. Characterisation of the fractions was attempted with TLC, HPLC, acidic hydrolysis, and chromatography over Sephadex LH-20. The UF-concentrate was shown to consist mainly of oligomeric to polymeric proanthocyanidins (PA). This fraction was found to exhibit significant antiviral activity against Herpes simplex virus type 1 (HSV-1). In addition, the UV-concentrate displayed radical scavenging properties, inhibited alpha-glucosidase as well as human leukocyte elastase (HLE), and exhibited strong antiphlogistic effects in the croton oil ear edema test in the mouse. With the exception of the antioxidant potential and the inhibition of HLE-action the lower molecular fraction possessed weaker activities and contained mainly hamamelitannin, catechin, and further, unidentified constituents.

Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic steatohepatitis in obese Ldlr-/- mice

PubMed Central

Lytle, Kelli A.; Wong, Carmen P.

2017-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments. Using Ldlr -/- mice as a preclinical model of western diet (WD)-induced NASH, we previously established that dietary supplementation with docosahexaenoic acid (DHA, 22:6,ω3) attenuated WD-induced NASH in a prevention study. Herein, we evaluated the capacity of DHA supplementation of the WD and a low fat diet to fully reverse NASH in mice with pre-existing disease. Methods Ldlr -/- mice fed the WD for 22 wks developed metabolic syndrome (MetS) and a severe NASH phenotype, including obesity, dyslipidemia, hyperglycemia, hepatic steatosis, inflammation, fibrosis and low hepatic polyunsaturated fatty acid (PUFA) content. These mice were randomized to 5 groups: a baseline group (WDB, sacrificed at 22 wks) and 4 treatments: 1) WD + olive oil (WDO); 2) WD + DHA (WDD); 3) returned to chow + olive oil (WDChO); or 4) returned to chow + DHA (WDChD). The four treatment groups were maintained on their respective diets for 8 wks. An additional group was maintained on standard laboratory chow (Reference Diet, RD) for the 30-wk duration of the study. Results When compared to the WDB group, the WDO group displayed increased hepatic expression of genes linked to inflammation (Opn, Il1rn, Gdf15), hepatic fibrosis (collagen staining, Col1A1, Thbs2, Lox) reflecting disease progression. Mice in the WDD group, in contrast, had increased hepatic C20-22 ω3 PUFA and no evidence of NASH progression. MetS and NASH markers in the WDChO or WDChD groups were significantly attenuated and marginally different from the RD group, reflecting disease remission. Conclusion While these studies establish that DHA supplementation of the WD blocks WD-induced NASH progression, DHA alone does not promote full remission of diet-induced MetS or NASH. PMID:28422962

Lamotriginium crotonate and lamotriginium salicylate ethanol monosolvate: the role of solvent molecules in the packing organization.

PubMed

Freire, Eleonora; Echeverría, Gustavo A; Baggio, Ricardo

2017-07-01

Two lamotriginium salts, namely lamotriginium crotonate [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium but-2-enoate, C 9 H 8 Cl 2 N 5 + ·C 4 H 5 O 2 - , (III)] and lamotriginium salicylate [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium 2-hydroxybenzoate ethanol monosolvate, C 9 H 8 Cl 2 N 5 + ·C 7 H 5 O 3 - ·C 2 H 5 OH, (IV)] present extremely similar centrosymmetric hydrogen-bonded A...L...L...A packing building blocks (L is lamotriginium and A is the anion). The fact that salicylate salt (IV) is (ethanol) solvated, while crotonate salt (III) is not, has a profound effect on the way these elemental units aggregate to generate the final crystal structure. Possible reasons for this behaviour are analyzed and the hypothesis raised checked against similar structures in the literature.

New sesquiterpene lactones from Arnica tincture prepared from fresh flowerheads of Arnica montana.

PubMed

Kos, Olha; Lindenmeyer, Maja T; Tubaro, Aurelia; Sosa, Silvio; Merfort, Irmgard

2005-11-01

Investigation of an ethanolic extract prepared from fresh Arnica montana flowers afforded three new 1,5- trans-guaianolides, of which 11alpha,13-dihydro-2-O-tigloylflorilenalin and the respective 2-O-isovaleryl derivative are reported for the first time. Additionally, three new and one known 2beta-ethoxy-2,3-dihydrohelenalin esters were isolated. GC/MS studies of the extract after a two year storage at 4 degrees C demonstrated that the latter were artefacts that had been formed by addition of ethanol to the cyclopentenone structure of helenalin. Formation of these adducts gave compounds possessing an inhibitory activity comparable to that of 11alpha,13-dihydrohelenalin derivatives in the NF-kappaB EMSA and the IL-8 ELISA in vitro assays as well as in the in vivo croton oil-induced mouse ear edema test for one adduct, namely 2beta-ethoxy-6-O-acetyl-2,3-dihydrohelenalin. As expected, 6-O-(2-methylbutyryl)- and 6-O-methacryloyl-helenalin exhibited a stronger activity in the NF-kappaB EMSA and IL-8 ELISA. Sesquiterpene lactones seem to be the most important NF-kappaB inhibiting compounds in the Arnica extract. Bioguided fractionation using the luciferase reporter gene assay resulted in the isolation of only moderately active compounds, such as 6-acetoxy-2,2-dimethylchroman-4-one and 10-acetoxy-8,9-epoxythymol isobutyrate.

Topical anti-inflammatory activity of Solanum corymbiflorum leaves.

PubMed

Piana, Mariana; Camponogara, Camila; Boligon, Aline Augusti; Machado, Michel Mansur; de Brum, Thiele Faccim; Oliveira, Sara Marchesan; de Freitas Bauermann, Liliane

2016-02-17

Solanum corymbiflorum is popularly known as "baga-de-veado" and its leaves are applied on inflamed legs, scabies, tick bite, boils, mastitis, low back pain and otitis. The aim of this study was evaluate anti-inflammatory in vivo activity and relate this activity with antioxidant compounds present in the extract of S. corymbiflorum leaves. The extract from S. corymbiflorum leaves topically applied was able to reduce the croton oil-induced ear edema and myeloperoxidase (MPO) activity with maximum inhibition of 87±3% and 45±7%, rescpectively in the dose of 1mg/ear. Similar results were found for positive control dexamethasone, which presented inhibitions of ear edema and MPO activity of 89±3% and 50±3%, respectively in a dose of 0.1mg/ear. These findings are due, at least in part, the presence of polyphenols (195.28mg GAE/g) and flavonoids, as chlorogenic acid (59.27mg/g), rutin (12.72mg/g), rosmarinic acid, caffeic acid and gallic acid found by high performance liquid chromatography (HPLC) analysis. This species showed potencial antioxidant by 1,1-diphenyl-2-picrylhydrazyl (DPPH), and carbonyl groups in proteins methods which may be related with the presence of this compounds. This species possess anti-inflammatory activity confirming their popular use for the local treatment of skin inflammatory disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dietary fructose augments ethanol-induced liver pathology.

PubMed

Thomes, Paul G; Benbow, Jennifer H; Brandon-Warner, Elizabeth; Thompson, Kyle J; Jacobs, Carl; Donohue, Terrence M; Schrum, Laura W

2017-05-01

Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers. Copyright © 2017 Elsevier Inc. All rights reserved.

Fish Oil Supplementation Reduces Heart Levels of Interleukin-6 in Rats with Chronic Inflammation due to Epilepsy

PubMed Central

Nejm, Mariana Bocca; Haidar, André Abou; Hirata, Aparecida Emiko; Oyama, Lila Missae; de Almeida, Antonio-Carlos Guimarães; Cysneiros, Roberta Monterazzo; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Scorza, Fulvio Alexandre

2017-01-01

Sudden unexpected death in epilepsy (SUDEP) is a major cause of premature death related to epilepsy. The causes of SUDEP remain unknown, but cardiac arrhythmias and asphyxia have been suggested as a major mechanism of this event. Inflammation has been implicated in the pathogenesis of both epilepsy and ventricular arrhythmia, with interleukin-6 (IL-6) being recognized as a crucial orchestrator of inflammatory states. Our group previously reported that levels of IL-6 were increased in the hearts of epileptic rats. In this scenario, anti-inflammatory actions are among the beneficial effects of fish oil dietary supplementation. This investigation revealed that elevated levels of IL-6 in the heart were markedly reduced in epileptic rats that were treated in the long-term with fish oil, suggesting protective anti-inflammatory actions against dangerously high levels of IL-6. Based on these findings, our results suggest beneficial effects of long-term intake of fish oil in reducing the inflammation associated with chronic epilepsy. PMID:28649227

Environmentally persistent free radicals and particulate emissions from the thermal degradation of Croton megalocarpus biodiesel.

PubMed

Mosonik, Bornes C; Kibet, Joshua K; Ngari, Silas M; Nyamori, Vincent O

2018-06-21

Pyrolysis of biodiesel at high temperatures may result in the formation of transient and stable free radicals immobilized on particulate emissions. Consequently, free radicals adsorbed on particulates are believed to be precursors for health-related illnesses such as cancer, cardiac arrest, and oxidative stress. This study explores the nature of free radicals and particulate emissions generated when Croton megalocarpus biodiesel is pyrolyzed at 600 °C in an inert environment of flowing nitrogen at a residence time of 0.5 s at 1 atm. The surface morphology of thermal emissions were imaged using a field emission gun scanning electron microscope (FEG SEM) while the radical characteristics were investigated using an electron paramagnetic resonance spectrometer (EPR). A g-value of 2.0024 associated with a narrow ∆Hp-p of 3.65 G was determined. The decay rate constant for the radicals was low (1.86 × 10 -8  s -1 ) while the half-life was long ≈ 431 days. The observed EPR characterization of Croton megalocarpus thermal particulates revealed the existence of free radicals typical of those found in coal. The low g-value and low decay rate constant suggests that the free radicals in particulates are possibly carbon-centered. The mechanistic channel for the formation of croton char from model biodiesel component (9-dodecenoic acid, methyl ester) has been proposed in this study.

Topical action of Buriti oil (Mauritia flexuosa L.) in myositis induced in rats.

PubMed

Barbosa, Marília Ursulino; Silva, Marcello de Alencar; Barros, Esmeralda Maria Lustosa; Barbosa, Margarida Ursulino; Sousa, Rayssilane Cardoso de; Lopes, Mateus Aguiar da Costa; Coelho, Nayana Pinheiro Machado de Freitas

2017-11-01

To analyze the topical effects of Buriti oil (Mauritia flexuosa L.) in induced myositis in rats. Thirty six male rats divided into three groups: Control group (C), induced myositis group (MI) and induced myositis group reated with Mauritia flexuosa L. (MT). After inducing myositis with 1% acetic acid, was topically applied 0.5 ml of Mauritia flexuosa L.extract on the posterior region of the right gastrocnemius muscle in animals belonging to group MT, for 7 and 14 days. The neutrophil number there was statistically significant difference, after 7 and 14 days, between groups C and MI (p <0.001) (p<0.01). The group MT there was a significant difference in relation to MI group in both experimental times with (p<0.001). The number of fibroblasts in the 14 days showed that when comparing the groups M and MT the differences were also significant (p<0.001). As for the DLL, in 7 days, there was a significant difference between group C and MI group (p <0.001). When considering the MT group, there was a significant difference in relation to the MI group (p <0.001). The extract of Mauritia flexuosa L. leaves lessened acute and chronic inflammation, increased fibroblast proliferation and reduced macroscopically edema.

Geraniol attenuates fibrosis and exerts anti-inflammatory effects on diet induced atherogenesis by NF-κB signaling pathway.

PubMed

Jayachandran, Muthukumaran; Chandrasekaran, Balaji; Namasivayam, Nalini

2015-09-05

Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammation, immune responses, cell survival and cell proliferation. Tissue remodeling plays a significant role during the phase of inflammation and oxidative stress. In our study we have evaluated the effect of geraniol (GOH), a natural terpenoid on oxidative stress, inflammation and tissue remodeling in experimental animals. Experimental animals (hamsters) were divided into four groups; group 1 were control animals; group 2 were animals fed GOH alone (100mg/kg b.w. p.o); group 3 were animals fed atherogenic diet (standard pellet diet+10% coconut oil+0.25% cholesterol); group 4 animals were fed atherogenic diet as in group 3+GOH (100mg/kg b.w). At the end of the experimental period animals were killed and liver, heart and aorta tissues were analyzed for lipid peroxidation markers, non enzymic antioxidants and collagen distribution using histological studies like Milligan's trichrome and Picrosirius red staining. As inflammation plays a key role in tissue remodeling we also targeted the key inflammatory cytokine, NF-κB. GOH supplementation greatly prevented the remodeling of tissues by enhancing the free radical scavenging and anti-inflammatory effects. Thus in conclusion it can be suggested that GOH (100mg/kg b.w) prevents the atherogenic diet induced fibrosis in experimental hamsters. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical Composition of Pinus roxburghii Bark Volatile Oil and Validation of Its Anti-Inflammatory Activity Using Molecular Modelling and Bleomycin-Induced Inflammation in Albino Mice.

PubMed

Labib, Rola M; Youssef, Fadia S; Ashour, Mohamed L; Abdel-Daim, Mohamed M; Ross, Samir A

2017-08-29

The chemical composition of Pinus roxburghii bark essential oil (PRO) was qualitatively and quantitatively determined using GC/FID and GC/MS. The anti-inflammatory activity was assessed in vitro by evaluating the binding percentages on the cannabinoids and opioids receptors. Bleomycin (BLM)-induced pulmonary inflammation in albino mice was adopted to assess PRO anti-inflammatory efficacy in vivo. In silico molecular modelling of its major components was performed on human glucocorticoids receptor (GR). Seventy-five components were identified in which longifolene (33.13%) and palmitic acid (9.34%) constituted the predominant components. No binding was observed on cannabinoid receptor type 1 (CB1), whereas mild binding was observed on cannabinoid receptor type 2 (CB2), delta , kappa , and mu receptors accounting for 2.9%, 6.9%, 10.9% and 22% binding. A significant in vivo activity was evidenced by reduction of the elevated malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF- α ) levels by 55.56%, 55.66%, 64.64%, 58.85% and 77.78% with concomitant elevation of superoxide dismutase (SOD) and catalase (CAT) activities comparable to BLM-treated group at 100 mg/kg body weight. In silico studies showed that palmitic acid exerted the fittest binding. PRO could serve as a potent anti-inflammatory natural candidate that should be supported by further clinical trials.

Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema.

PubMed

Games, Ellen; Guerreiro, Marina; Santana, Fernanda R; Pinheiro, Nathalia M; de Oliveira, Emerson A; Lopes, Fernanda D T Q S; Olivo, Clarice R; Tibério, Iolanda F L C; Martins, Mílton A; Lago, João Henrique G; Prado, Carla M

2016-10-20

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes ( p -cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Mices received porcine pancreatic elastase (PPE) and were treated with p -cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma ( p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide ( p < 0.05). Monoterpenes p -cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.

Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

PubMed Central

Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

2015-01-01

Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver.

PubMed

Shewale, Swapnil V; Boudyguina, Elena; Zhu, Xuewei; Shen, Lulu; Hutchins, Patrick M; Barkley, Robert M; Murphy, Robert C; Parks, John S

2015-06-01

Echium oil (EO), which is enriched in 18:4 n-3, the immediate product of fatty acid desaturase 2 (FADS2) desaturation of 18:3 n-3, is as atheroprotective as fish oil (FO). The objective of this study was to determine whether botanical oils enriched in the FADS2 products 18:3 n-6 versus 18:4 n-3 are equally atheroprotective. LDL receptor KO mice were fed one of four atherogenic diets containing 0.2% cholesterol and 10% calories as palm oil (PO) plus 10% calories as: 1) PO; 2) borage oil (BO; 18:3 n-6 enriched); 3) EO (18:4 n-3 enriched); or 4) FO for 16 weeks. Mice fed BO, EO, and FO versus PO had significantly lower plasma total and VLDL cholesterol concentrations; hepatic neutral lipid content and inflammation, aortic CE content, aortic root intimal area and macrophage content; and peritoneal macrophage inflammation, CE content, and ex vivo chemotaxis. Atheromas lacked oxidized CEs despite abundant generation of macrophage 12/15 lipooxygenase-derived metabolites. We conclude that botanical oils enriched in 18:3 n-6 and 18:4 n-3 PUFAs beyond the rate-limiting FADS2 enzyme are equally effective in preventing atherosclerosis and hepatosteatosis compared with saturated/monounsaturated fat due to cellular enrichment of ≥20 PUFAs, reduced plasma VLDL, and attenuated macrophage inflammation. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.

PubMed

Georgiou, Tassos; Wen, Yao-Tseng; Chang, Chung-Hsing; Kolovos, Panagiotis; Kalogerou, Maria; Prokopiou, Ekatherine; Neokleous, Anastasia; Huang, Chin-Te; Tsai, Rong-Kung

2017-03-01

The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION). The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects. Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group. The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.

Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.

PubMed

Rodrigues, Lindaiane Bezerra; Oliveira Brito Pereira Bezerra Martins, Anita; Cesário, Francisco Rafael Alves Santana; Ferreira E Castro, Fyama; de Albuquerque, Thaís Rodrigues; Martins Fernandes, Maria Neyze; Fernandes da Silva, Bruno Anderson; Quintans Júnior, Lucindo José; da Costa, José Galberto Martins; Melo Coutinho, Henrique Douglas; Barbosa, Roseli; Alencar de Menezes, Irwin Rose

2016-09-25

The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Liver Disease, Systemic Inflammation, and Growth Using a Mixed Parenteral Lipid Emulsion, Containing Soybean Oil, Fish Oil, and Medium Chain Triglycerides, Compared With Soybean Oil in Parenteral Nutrition-Fed Neonatal Piglets.

PubMed

Turner, Justine M; Josephson, Jessica; Field, Catherine J; Wizzard, Pamela R; Ball, Ronald O; Pencharz, Paul B; Wales, Paul W

2016-09-01

The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure-associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω-6 and ω-3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil-based emulsion (ω-6:ω-3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (ω-6:ω-3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Neonatal piglets, 3-6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C-reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Compared with the IL group, ML-treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω-6 long-chain PUFA content was lower in plasma and brain for the ML group. The key ω-3 long-chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. The mixed lipid, having less ω-6 PUFA and more ω-3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN-fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes. © 2015 American Society for Parenteral and Enteral Nutrition.

Could essential oils enhance biopolymers performance for wound healing? A systematic review.

PubMed

Pérez-Recalde, Mercedes; Ruiz Arias, Ignacio E; Hermida, Élida B

2018-01-01

Millions of people in the world suffer from chronic wounds of different etiologies such as diabetic foot and leg ulcers, without solutions nowadays. Molecules obtained from plants offer an alternative to aid wound healing. Strong evidence about essential oils (EO) anti-inflammatory and antimicrobial properties is thoroughly described in literature and their chemical compositions are well characterized. More recently, EO effects in experimental wounds have begun to be analyzed. We aim to summarize the evidence of EO in experimental wounds, and the possibility of combining them with biopolymers commonly used in skin regeneration. Electronic databases such as ScienceDirect, PubMed and Scopus were used to search scientific contributions until March 2017, using relevant keywords. In a first step, literature focusing on EO and/or mono- or sesqui-terpenoids effects in rodent wounds was identified and summarized. In all cases, chemical structures and EO composition were detailed, as well as references to in vitro activities previously determined, e.g. antibacterial, antioxidant or anti-inflammatory. In a second step, scientific literature devoted to combine EO and biopolymers with the focus set on wound healing innovations, was collected and analyzed. Treatments with EO from species of genders Lavandula, Croton, Blumea, Eucalyptus, Pinus, Cymbopogon, Eucalyptus, Cedrus, Abies, Rosmarinus, Origanum, Salvia and Plectranthus, have shown positive results in rodent wounds. All of these EO were mainly composed by monoterpenoids-thymol, 1,8-cineole, linalool-or monoterpenes, as limonene or pinenes. Experimental wounds in rodents have shown faster closure rate, better collagen deposition and/or enhanced fibroblasts proliferation. In blends with biopolymers, several EO combined with chitosan, alginate, gelatin or collagen, were processed to give active films or nanofibers, with antioxidant, anti-inflammatory or antimicrobial activities. Curiously, all of these works were carried out since 2010. There is significant evidence about the effectivity of EO as wound healers. The incorporation of EO into a polymer matrix that contributes to wound healing is still incipient. However, scientific based evidence of the EO incorporation in resorbable polymeric scaffolds was found and analyzed herein. In summary, EO-biopolymer dressings or scaffolds have become promising artifacts regarding wound treatments, especially in chronic wounds, where treating infection and inflammation are still important issues. Copyright © 2017 Elsevier GmbH. All rights reserved.

Acute exposure to Buenos Aires air particles (UAP-BA) induces local and systemic inflammatory response in middle-aged mice: A time course study.

PubMed

Orona, Nadia S; Ferraro, Sebastián A; Astort, Francisco; Morales, Celina; Brites, Fernando; Boero, Laura; Tiscornia, Gisela; Maglione, Guillermo A; Saldiva, Paulo H N; Yakisich, Sebastian; Tasat, Deborah R

2016-01-01

Exposure to air particulate matter (PM) is associated with increased cardiovascular morbimortality. However, PM doesn't affect equally to all people, being the old cohort the most susceptible and studied. We hypothesized that another specific life phase, the middle-aged subpopulation, may be negatively affected. Therefore, the aim of this study was to analyze in vivo the acute biological impact of two environmental particles, Urban Air Particles from Buenos Aires and Residual Oil Fly Ash, on the cardiorespiratory system of middle-aged mice, evaluating oxidative metabolism and inflammation. Both PM provoked a local and systemic inflammatory response, leading to a reduced alveolar area in the lung, an epicard inflammation in the heart, an increment of IL-6, and a reduction on PON 1 activity in serum of middle-aged animals. The positive correlation of local parameters with systemic markers of oxidative stress and inflammation could be responsible for associations of cardiovascular morbimortality in this subpopulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serum paraoxonase type-1 activity in pigs: assay validation and evolution after an induced experimental inflammation.

PubMed

Escribano, Damián; Tvarijonaviciute, Asta; Tecles, Fernando; Cerón, José J

2015-02-15

Paraoxonase 1 (PON1) is a serum enzyme synthesised and secreted primarily by the liver. It possesses anti-inflammatory properties limiting the production of pro-inflammatory mediators. The objectives of this study were to validate three spectrophotometric assays for the quantification of PON1 activity in pig serum, and to determine if PON1 activity in porcine behaves as a negative acute phase protein (APP), decreasing in inflammatory conditions. An analytical validation using three different substrates - 5-thiobutil butyrolactone (TBBL), phenylacetate (PA) and 4-(p)-nitrophenyl acetate (pNA) - was performed. In addition, inflammation was experimentally induced in five pigs by subcutaneous injection of turpentine oil, while five control pigs were left untreated. The treated pigs showed significant increases in CRP and decreases in albumin, indicating an inflammatory condition. The three substrates used would be suitable for PON1 activity measurements in serum samples, since they offer adequate precision (coefficients of variation<10%), sensitivity (0.01, 0.15, 0.02 U/mL for TBBL, pNA and PA respectively) and accuracy (r=0.99). In addition, PON1 behaves as a negative APP in pigs since a significant decrease (P<0.05) in its activity after 72 h of the induction of the inflammation was observed with all substrates. Copyright © 2015 Elsevier B.V. All rights reserved.

Oil from the fruits of Pterodon emarginatus Vog.: A traditional anti-inflammatory. Study combining in vivo and in silico.

PubMed

Dos Santos, Cleydson Breno Rodrigues; da Silva Ramos, Ryan; Ortiz, Brenda Lorena Sánchez; da Silva, Gabriel Monteiro; Giuliatti, Silvana; Balderas-Lopez, José Luis; Navarrete, Andrés; Carvalho, José Carlos Tavares

2018-08-10

The oil obtained from the fruits of Pterodon emarginatus Vog. (OPe) is used orally and topically, in traditional medicine for some purposes, such as acute and chronic inflammatory states as rheumatoid arthritis. In this work, the anti-inflammatory activity of the OPe was demonstrated based on several animal models and presented an in silico study based on the 6α,7β-dihydroxy-vouacapan-17β-oic acid (DHVA) majority compound of the OPe to evaluate the interaction this compound, with cyclooxygenase-2 (COX-2) in 4COX (Mus musculus) and 5KIR (Homo sapiens) and molecular dynamics simulation. The OPe (498 mg/kg, p.o) significantly inhibited (p < 0.05, Student t-test) the primary and secondary reactions of arthritis by Freund's Complete Adjuvant (FCA) and in dermatitis induced by croton oil in mice, OPe inhibited peak of edema. In vascular permeability test in rats, the treatment with OPe was able to block the response to PGE 2 , serotonin, and bradykinin (p < 0.05, Student t-test). In the writhing test in mice, the OPe at doses of 498 and 980 mg/kg (p.o) produced inhibition of 73% and 92%, respectively, and was not significantly effective in the hot plate test. In the evaluation of the potency in relation to gastric injury (gastric ulcer induced by stress) and combined assay in the assessment of anti-inflammatory potency and gastric damage, it was observed that indomethacin (10 mg/kg, p.o.) inhibited carrageenan edema by 51% and produced a higher number of gastric lesions when compared to the group treated with OPe, where only areas of hyperemia were observed, without the occurrence of ulcerative lesion, and which inhibited the edema by 47%. In the in silico study, it was found that the DHVA is capable of binding to two organisms (4COX - Mus musculus and 5KIR - Homo sapiens), however, with higher binding affinity to the organism Homo sapiens. As expected, all tested ligands were capable of forming hydrogen interactions with residues at their respective binding sites, but the DHVA ligand was capable of creating slightly more hydrogen bonds when docked to either 4COX or 5KIR than the other tested ligands, thus demonstrating the participation of this compound in the anti-inflammatory and antialgic responses observed in the in vivo assays as a COX-2 inhibitor. Therefore, the results obtained support the traditional use of OPe for inflammatory and gastric problems. Copyright © 2018 Elsevier B.V. All rights reserved.

Olive Oil and Vitamin D Synergistically Prevent Bone Loss in Mice

PubMed Central

Tagliaferri, Camille; Davicco, Marie-Jeanne; Lebecque, Patrice; Georgé, Stéphane; Amiot, Marie-Jo; Mercier, Sylvie; Dhaussy, Amélie; Huertas, Alain; Walrand, Stéphane; Wittrant, Yohann; Coxam, Véronique

2014-01-01

As the Mediterranean diet (and particularly olive oil) has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH) or ovariectomized (OVX) mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation. PMID:25551374

Flaxseed and Flaxseed Oil

MedlinePlus

... oil are used as dietary supplements for constipation, diabetes, cholesterol, cancer, and other conditions. Flaxseed is made ... flaxseed for ovarian cancer, cardiovascular disease, metabolic syndrome, diabetes, asthma, and inflammation. What Do We Know About ...

The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity

PubMed Central

Khazdair, Mohammad Reza

2015-01-01

Nigella sativa (N. sativa) is an annual plant and widely used as medicinal plant throughout the world. The seeds of the plant have been used traditionally in various disorders and as a spice to ranges of Persian foods. N. sativa has therapeutic effects on tracheal responsiveness (TR) and lung inflammation on induced toxicity by Sulfur mustard. N. sativa has been widely used in treatment of various nervous system disorders such as Alzheimer disease, epilepsy, and neurotoxicity. Most of the therapeutic properties of this plant are due to the presence of some phenolic compounds especially thymoquinone (TQ), which is major bioactive component of the essential oil. The present review is an effort to provide a comprehensive study of the literature on scientific researches of pharmacological activities of the seeds of this plant on induced neurotoxicity. PMID:26604923

Croton membranaceus Improves Some Biomarkers of Cardiovascular Disease and Diabetes in Genetic Animal Models.

PubMed

Asare, George Awuku; Adjei, Samuel; Afriyie, Daniel; Appiah-Danquah, Akua Bempomaa; Asia, Jonas; Asiedu, Bernice; Santa, Sheila; Doku, Derek

2015-12-01

Cardiovascular disease (CVD) accounts for 17.3 million deaths per year globally. In Ghana, CVD accounts for 22.2% of deaths. Croton membranaceus (CM) Mull. Arg. (Euphorbiaceae), a medicinal plant in Ghana is mainly used traditionally for the treatment of benign prostatic hyperplasia and measles. However, some hypoglycaemic and hypotensive effects have recently been reported but not scientifically examined. The study aimed at establishing whether Croton membranaceus (CM) used for prostatitis had any effect on CVD markers. In experiment 1, lipid profile changes were determined. Twenty four male Spontaneously Hypertensive Rats (SHR) were divided into 4 groups. Low (LD), intermediate (ID) and high dose (HD) groups received 25, 50 and 100 mg/kg b.wt. CM aqueous root extracts (CMARE) for 60 days, respectively, the controls received distilled water. In experiment 2, blood glucose levels (BGL) were determined. 21 db/db mice were divided into 3 groups of 7 mice each alongside db/+ mice (7) (negative control). Groups 1 and 2 received 250 mg/kg b.wt CMARE and metformin, respectively. Group 3 (positive control) and db/+ mice (negative control) received distilled water. Mice were monitored for 15 hours. Data collected were analysed using SPSS version 20. Hypotriglyceridaemic effect was observed (p=0.005). High Density Lipoprotein cholesterol (HDL) and Low Density Lipoprotein cholesterol (LDL) showed significant increases (p=0.013) and decreases (p=0.003), respectively. A significant CRP reduction was observed for ID and HD groups (p = 0.010, p = 0.011, respectively). BGL was reduced in Metformin and Croton groups (p=0.000; p= 0.006, respectively) after 3 hours. In conclusion, CMARE has positive effects on some CVD biomarkers and a hypoglycaemic effect.

Croton membranaceus Improves Some Biomarkers of Cardiovascular Disease and Diabetes in Genetic Animal Models

PubMed Central

Adjei, Samuel; Afriyie, Daniel; Appiah-Danquah, Akua Bempomaa; Asia, Jonas; Asiedu, Bernice; Santa, Sheila; Doku, Derek

2015-01-01

Introduction Cardiovascular disease (CVD) accounts for 17.3 million deaths per year globally. In Ghana, CVD accounts for 22.2% of deaths. Croton membranaceus (CM) Mull. Arg. (Euphorbiaceae), a medicinal plant in Ghana is mainly used traditionally for the treatment of benign prostatic hyperplasia and measles. However, some hypoglycaemic and hypotensive effects have recently been reported but not scientifically examined. Aim The study aimed at establishing whether Croton membranaceus (CM) used for prostatitis had any effect on CVD markers. Materials and Methods In experiment 1, lipid profile changes were determined. Twenty four male Spontaneously Hypertensive Rats (SHR) were divided into 4 groups. Low (LD), intermediate (ID) and high dose (HD) groups received 25, 50 and 100 mg/kg b.wt. CM aqueous root extracts (CMARE) for 60 days, respectively, the controls received distilled water. In experiment 2, blood glucose levels (BGL) were determined. 21 db/db mice were divided into 3 groups of 7 mice each alongside db/+ mice (7) (negative control). Groups 1 and 2 received 250 mg/kg b.wt CMARE and metformin, respectively. Group 3 (positive control) and db/+ mice (negative control) received distilled water. Mice were monitored for 15 hours. Data collected were analysed using SPSS version 20. Results Hypotriglyceridaemic effect was observed (p=0.005). High Density Lipoprotein cholesterol (HDL) and Low Density Lipoprotein cholesterol (LDL) showed significant increases (p=0.013) and decreases (p=0.003), respectively. A significant CRP reduction was observed for ID and HD groups (p = 0.010, p = 0.011, respectively). BGL was reduced in Metformin and Croton groups (p=0.000; p= 0.006, respectively) after 3 hours. Conclusion In conclusion, CMARE has positive effects on some CVD biomarkers and a hypoglycaemic effect. PMID:26816938

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels

PubMed Central

Xu, Jian Hui; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

2017-01-01

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high-fat diet-mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon-like peptide-1 and −2, peptide YY, glucose-dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high-fat diet-fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance. PMID:28447763

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels.

PubMed

Xu, Jian Hui; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

2017-05-01

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high‑fat diet‑mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon‑like peptide‑1 and ‑2, peptide YY, glucose‑dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high‑fat diet‑fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance.

Evaluation of the Anti-Inflammatory and Antinociceptive Effects of the Essential Oil from Leaves of Xylopia laevigata in Experimental Models

PubMed Central

Queiroz, João Carlos C.; Antoniolli, Ângelo R.; Quintans-Júnior, Lucindo J.; Brito, Renan G.; Barreto, Rosana S. S.; Costa, Emmanoel V.; da Silva, Thanany B.; Prata, Ana Paula Nascimento; de Lucca, Waldecy; Almeida, Jackson R. G. S.; Lima, Julianeli T.; Quintans, Jullyana S. S.

2014-01-01

Xylopia laevigata (Annonaceae) is a medicinal plant used in folk medicine to treat pain and inflammation. Thus, we investigated the possible antioxidant, antinociceptive, and anti-inflammatory effects of X. laevigata leaf essential oil (EOX) in animal models. Our EOX sample showed the presence of γ-muurolene (17.78%), δ-cadinene (12.23%), bicyclogermacrene (7.77%), and α-copaene (7.17%) as main compounds. EOX presented a strong antioxidant potential according to the DPPH, TBARS, and nitrite production tests. Additionally, pretreatment with EOX, in mice, also significantly produced (P < 0.05 or P < 0.001) antinociceptive effect by reduction of nociceptive behavior (in formalin and writhing tests). The EOX showed c-Fos label in the olfactory bulb, piriform cortex, and periaqueductal gray. Acute administration of EOX exhibited a significant (P < 0.01 or P < 0.001) anti-inflammatory profile in the carrageenan-induced peritonitis and by the carrageenan-induced hindpaw edema tests in mice. Our results provide evidence for the use of X. laevigata by traditional medicine practitioners in the management of pain and inflammatory disorders. PMID:25097889

Evaluation of the anti-inflammatory and antinociceptive effects of the essential oil from leaves of Xylopia laevigata in experimental models.

PubMed

Queiroz, João Carlos C; Antoniolli, Angelo R; Quintans-Júnior, Lucindo J; Brito, Renan G; Barreto, Rosana S S; Costa, Emmanoel V; da Silva, Thanany B; Prata, Ana Paula Nascimento; de Lucca, Waldecy; Almeida, Jackson R G S; Lima, Julianeli T; Quintans, Jullyana S S

2014-01-01

Xylopia laevigata (Annonaceae) is a medicinal plant used in folk medicine to treat pain and inflammation. Thus, we investigated the possible antioxidant, antinociceptive, and anti-inflammatory effects of X. laevigata leaf essential oil (EOX) in animal models. Our EOX sample showed the presence of γ-muurolene (17.78%), δ-cadinene (12.23%), bicyclogermacrene (7.77%), and α-copaene (7.17%) as main compounds. EOX presented a strong antioxidant potential according to the DPPH, TBARS, and nitrite production tests. Additionally, pretreatment with EOX, in mice, also significantly produced (P < 0.05 or P < 0.001) antinociceptive effect by reduction of nociceptive behavior (in formalin and writhing tests). The EOX showed c-Fos label in the olfactory bulb, piriform cortex, and periaqueductal gray. Acute administration of EOX exhibited a significant (P < 0.01 or P < 0.001) anti-inflammatory profile in the carrageenan-induced peritonitis and by the carrageenan-induced hindpaw edema tests in mice. Our results provide evidence for the use of X. laevigata by traditional medicine practitioners in the management of pain and inflammatory disorders.

Comparison of potential preventive effects of pomegranate flower, peel and seed oil on insulin resistance and inflammation in high-fat and high-sucrose diet-induced obesity mice model.

PubMed

Harzallah, Arij; Hammami, Mohamed; Kępczyńska, Malgorzata A; Hislop, David C; Arch, Jonathan R S; Cawthorne, Michael A; Zaibi, Mohamed S

2016-01-01

The potentially beneficial effects of pomegranate peel (PPE), flower (PFE) and seed oil (PSO) extracts, in comparison with rosiglitazone, on adiposity, lipid profile, glucose homoeostasis, as well as on the underlying inflammatory mechanisms, were examined in high-fat and high-sucrose (HF/HS) diet-induced obese (DIO) mice. Body weight, body fat, energy expenditure, food and liquid intake, blood glucose, and plasma levels of insulin, lipids and cytokines were measured. After two weeks, PSO (2 ml/kg/day) and rosiglitazone (3 mg/kg/day) had not improved glucose intolerance. After 4 weeks, both treatments significantly reduced fasting blood glucose and an insulin tolerance test showed that they also improved insulin sensitivity. Treatment with PPE, PFE and PSO, reduced the plasma levels of the pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), and PFE increased the level of the anti-inflammatory cytokine interleukin-10 (IL-10). PPE, PFE and PSO have anti-inflammatory properties. PSO also improved insulin sensitivity.

The radioprotective activities of turpentine-induced inflammation and alpha2-macroglobulin: the effect of dexamethasone on the radioprotective efficacy of the inflammation.

PubMed

Sevaljević, Ljiljana; Dobrić, Silva; Bogojević, Desanka; Petrović, Miodrag; Koricanać, Goran; Vulović, Mojca; Kanazir, Dusan; Ribarac-Stepić, Nevena

2003-03-01

This work was aimed at the radioprotective efficacy of turpentine oil (TO), alpha2-Macroglobulin (alpha2-M), Amifostine (Ami) and/or dexamethasone (Dex). These agents were administrated, alone or in combination, prior to irradiation of rats with 6.7 Gy (LD(50/30)). The survival was recorded daily for 4 weeks after irradiation and body weight, peripheral leukocytes and thrombocytes were measured. The plasma concentration of alpha2-M and other acute phase proteins were determined by crossed immunoelectrophoresis. All rats receiving alpha2-M and Ami alone or in combination survived the radiation injury, whereas the rate of survival of TO-treated rats was 90%. Radiation and therapy-induced changes in the expression of acute phase protein genes were atypical for the acute phase reaction. Dex alone was lethal for 45% and 55% of control and irradiated rats, respectively. Pretreatment with 1mg Dex reduced radioprotective efficacy of TO and Ami to 30% and 40%, respectively. Given together TO and Ami provided 70% protection to rats receiving Dex. The TO and alpha2-M enhanced the rate of survival from 50% to 90% and 100%, respectively. In the presence of 1mg Dex the TO-induced radioprotectors and Ami exhibited radiosensitizing rather than radioprotecting activities.

Analysis of the temporal expression of chemokines and chemokine receptors during experimental granulomatous inflammation: role and expression of MIP-1α and MCP-1

PubMed Central

Carollo, Maria; Hogaboam, Cory M; Kunkel, Stephen L; Delaney, Stephen; Christie, Mark I; Perretti, Mauro

2001-01-01

Chemokine expression and function was monitored in an experimental model of granulomatous tissue formation after injection of croton oil in complete Freund's adjuvant (CO/CFA) into mouse dorsal air-pouches up to 28 days. In the first week, mast cell degranulation and leukocyte influx (mononuclear cell, MNC, and polymorphonuclear cell, PMN) were associated with CXCR2, KC and macrophage inflammatory protein (MIP)-2 mRNA expression, as determined by TaqMan® reverse transcriptase-polymerase chain reaction. KC (∼400 pg mg protein−1, n=12) and MIP-2 (∼800 pg mg protein−1, n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity. Highest MIP-1α (>1 ng mg protein−1, n=12) levels were measured at day 3. After day 7, a gradual increase in CCR2 and CCR5 mRNA, monocyte chemoattractant protein (MCP)-1 mRNA and protein expression was measured. MCP-1 protein peaked at day 21 (∼150 pg mg protein−1, n=12) and was predominantly expressed by mast cells. A gradual increase in N-acetyl-β-D-glucosaminidase (NAG) activity (maximal at 28 days) was also measured. An antiserum against MIP-1α did not modify the inflammatory response measured at day 7 (except for a 50% reduction in MIP-1α levels), but provoked a significant increase in MPO, NAG and MCP-1 levels as measured at day 21 (n=6, P<0.05). An antiserum to MCP-1 reduced NAG activity at day 21 but increased MPO activity values (n=8, P<0.05). In conclusion, we have shown that CO/CFA initiates a complex inflammatory reaction in which initial expression of MIP-1α serves a protective role whereas delayed expression of MCP-1 seems to have a genuine pro-inflammatory role. PMID:11704636

Vitamin A Status of Women and Children in Yaoundé and Douala, Cameroon, is Unchanged One Year after Initiation of a National Vitamin A Oil Fortification Program

PubMed Central

Engle-Stone, Reina; Nankap, Martin; Ndjebayi, Alex; Gimou, Marie-Madeleine; Friedman, Avital; Haskell, Marjorie J.; Tarini, Ann; Brown, Kenneth H.

2017-01-01

Vitamin A (VA) fortification of cooking oil is considered a cost-effective strategy for increasing VA status, but few large-scale programs have been evaluated. We conducted representative surveys in Yaoundé and Douala, Cameroon, 2 years before and 1 year after the introduction of a mandatory national program to fortify cooking oil with VA. In each survey, 10 different households were selected within each of the same 30 clusters (n = ~300). Malaria infection and plasma indicators of inflammation and VA (retinol-binding protein, pRBP) status were assessed among women aged 15–49 years and children aged 12–59 months, and casual breast milk samples were collected for VA and fat measurements. Refined oil intake was measured by a food frequency questionnaire, and VA was measured in household oil samples post-fortification. Pre-fortification, low inflammation-adjusted pRBP was common among children (33% <0.83 µmol/L), but not women (2% <0.78 µmol/L). Refined cooking oil was consumed by >80% of participants in the past week. Post-fortification, only 44% of oil samples were fortified, but fortified samples contained VA concentrations close to the target values. Controlling for age, inflammation, and other covariates, there was no difference in the mean pRBP, mean breast milk VA, prevalence of low pRBP, or prevalence of low milk VA between the pre- and post-fortification surveys. The frequency of refined oil intake was not associated with VA status indicators post-fortification. In sum, after a year of cooking oil fortification with VA, we did not detect evidence of increased plasma RBP or milk VA among urban women and preschool children, possibly because less than half of the refined oil was fortified. The enforcement of norms should be strengthened, and the program should be evaluated in other regions where the prevalence of VA deficiency was greater pre-fortification. PMID:28531099

[Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjögren's syndrome patients].

PubMed

Pinheiro, Manuel Neuzimar; dos Santos, Procópio Miguel; dos Santos, Regina Cândido Ribeiro; Barros, Jeison de Nadai; Passos, Luiz Fernando; Cardoso Neto, José

2007-01-01

To evaluate if oral flaxseed oil (Linum usitatissimum), which reduces the inflammation in rheumatoid arthritis, may help keratoconjunctivitis sicca's treatment in Sjögren's syndrome patients. In a randomized clinical trial, 38 female patients with rheumatoid arthritis or systemic lupus erithematosus associated with keratoconjunctivitis sicca and Sjögren's syndrome were consecutively selected from patients of the Department of Rheumatology of the Amazonas University Hospital. Keratoconjunctivitis sicca diagnosis was based on a dry-eye symptom survey score (Ocular Surface Disease Index - OSDI), Schirmer-I test, fluorescein break-up time, 1% Rose Bengal staining of ocular surface measured by the van Bijsterveld scale. All patients had ocular surface inflammation evaluated and quantified by conjunctival impression cytology, before and after the study. The subjects were divided into three groups with 13 (Group I), 12 (Group II) and 13 (Group III) patients. Group I received flaxseed oil capsules with a final 1 g/day dosis, Group II flaxseed oil capsules with a final 2 g/day dosis and Group III - controls - placebo, for 180 days. Comparing the results at the beginning and at the end of the treatment, statistically significant changes (p<0.05) in symptoms (OSDI), ocular surface inflammation quantified by conjunctival impression cytology, Schirmer-I test and fluorescein break-up time occurred in Groups I e II when compared to controls. Therapy with oral flaxseed oil capsules 1 or 2 g/day reduces ocular surface inflammation and ameliorates the symptoms of keratoconjunctivitis sicca in Sjögren's syndrome patients. Long-term studies are needed to confirm the role of this therapy for keratoconjunctivitis sicca in Sjögren's syndrome.

Anti-inflammatory activity of niosomes entrapped with Plai oil (Zingiber cassumunar Roxb.) by therapeutic ultrasound in a rat model

PubMed Central

Leelarungrayub, Jirakrit; Manorsoi, Jiradej; Manorsoi, Aranya

2017-01-01

Objective The aim of this study was to evaluate the antioxidant and anti-inflammatory activities of Plai oil–encapsulated niosomes (Zingiber cassumunar Roxb.) on inflamed subcutaneous Wistar rat skin by therapeutic ultrasound. Methods Pure oil from Plai rhizomes was extracted by steam distillation, and antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. Bioactive compounds were analyzed by gas chromatography-mass spectrometry. Niosome particles containing Plai oil were prepared by chloroform film method with sonication before testing for anti-inflammatory activity on locally inflamed subcutaneous rat skin after inducement from lipopolysaccharide with ultrasound once a day for 3 days. Skin temperatures and blood flow were evaluated. Results Plai oil presented antioxidant activity that inhibited 2,2-diphenyl-1-picrylhydrazyl radicals. Four active compounds found in the essential oil were sabinene, γ-terpinene, terpinene-4-ol, and (E)-1-(3,4-dimethyoxy phenyl) butadiene. Application of ultrasound (0.2 W/cm2, 20%, 3 min) with gel containing Plai oil–encapsulated niosomes decreased skin temperature and blood flow to the lowest level compared to the application of neurofen drug or gel-based control. Conclusion Plai oil, which consists of four main bioactive compounds and possesses antioxidant and anti-inflammatory activities, can be applied against local subcutaneous inflammation when used with therapeutic ultrasound via entrapped niosomes. PMID:28408818

Diterpenes and other constituents from Croton draco (Euphorbiaceae).

PubMed

Murillo, R M; Jakupovic, J; Rivera, J; Castro, V H

2001-03-01

Croton draco (Euphorbiaceae) from Guadalupe, San José, Costa Rica was collected in July 1992 and phytochemically studied (leaves, seeds, wood, bark, sap and flowers separately). Commonly known compounds such as 1-hydroxyjunenol, p-hydroxybenzaldehyde, p-methoxybenzoic acid, 3,4,5-trimethoxycinnamyl alcohol, the coumarin scopoletin, the nor-terpenoids 9-dehydrovomifoliol and 2,3-dihydrovomifoliol were obtained. Taspine, two aporphinic alkaloids, the diterpenes 9(11)-dehydrokaurenic acid, hardwikiic acid, the corresponding new 12-oxo derivative as well as five clerodanes and a phorbol ester were also isolated. Three clerodanes were not previously described and their NMR spectroscopical data and MS fragmentation patterns are reported.

Complement inhibiting properties of dragon's blood from Croton draco.

PubMed

Tsacheva, Ivanka; Rostan, Joerg; Iossifova, Tania; Vogler, Bernhard; Odjakova, Mariela; Navas, Hernan; Kostova, Ivanka; Kojouharova, Michaela; Kraus, Wolfgang

2004-01-01

The latex of Croton draco, its extracts and several latex components have been investigated for their influence on both classical (CP) and alternative (AP) activation pathways of the complement system using a hemolytic assay. The best inhibition was found for the classical pathway. The latex, ethyl acetate and ethyl ether extracts exhibited extremely high inhibition on the CP (94, 90 and 77%, respectively) at a concentration of 1 mg/ml. The flavonoid myricitrin, the alkaloid taspine and the cyclopeptides P1 and P2 showed high inhibition on CP (83, 91, 78 and 63%, respectively) at a concentration of 0.9 mM.

Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model.

PubMed

Zhu, Huiling; Wang, Haibo; Wang, Shuhui; Tu, Zhixiao; Zhang, Lin; Wang, Xiuying; Hou, Yongqing; Wang, Chunwei; Chen, Jie; Liu, Yulan

2018-05-01

Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigates the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs 5% flaxseed oil) and LPS challenge (saline vs LPS). On day 21 of the experiment, pigs were administrated with LPS or saline. At 2 h and 4 h post-administration, blood samples were collected. After the blood harvest at 4 h, all piglets were slaughtered and intestinal samples were collected. Flaxseed oil supplementation led to the enrichment of ALA, EPA, and total n-3 PUFAs in intestine. Flaxseed oil improved intestinal morphology, jejunal lactase activity, and claudin-1 protein expression. Flaxseed oil downregulated the mRNA expression of intestinal necroptotic signals. Flaxseed oil also downregulated the mRNA expression of intestinal toll-like receptors 4 (TLR4) and its downstream signals myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and nucleotide-binding oligomerization domain proteins 1, 2 (NOD1, NOD2) and its adapter molecule, receptor-interacting protein kinase 2 (RIPK2). These results suggest that dietary addition of flaxseed oil enhances intestinal integrity and barrier function, which is involved in modulating necroptosis and TLR4/NOD signaling pathways. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats

PubMed Central

2011-01-01

Background Trans-fatty acids (TFA) are known as a risk factor for coronary artery diseases, insulin resistance and obesity accompanied by systemic inflammation, the features of metabolic syndrome. Little is known about the effects on the liver induced by lipids and also few studies are focused on the effect of foods rich in TFAs on hepatic functions and oxidative stress. This study investigates whether high-fat diets with different TFA levels induce oxidative stress and liver dysfunction in rats. Methods Male Wistar rats were divided randomly into four groups (n = 12/group): C receiving standard-chow; Experimental groups that were fed high-fat diet included 20% fresh soybean oil diet (FSO), 20% oxidized soybean oil diet (OSO) and 20% margarine diet (MG). Each group was kept on the treatment for 4 weeks. Results A liver damage was observed in rats fed with high-fat diet via increase of liver lipid peroxidation and decreased hepatic antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase). The intake of oxidized oil led to higher levels of lipid peroxidation and a lower concentration of plasma antioxidants in comparison to rats fed with FSO. The higher inflammatory response in the liver was induced by MG diet. Liver histopathology from OSO and MG groups showed respectively moderate to severe cytoplasm vacuolation, hypatocyte hypertrophy, hepatocyte ballooning, and necroinflammation. Conclusion It seems that a strong relationship exists between the consumption of TFA in the oxidized oils and lipid peroxidation and non alcoholic fatty liver disease (NAFLD). The extent of the peroxidative events in liver was also different depending on the fat source suggesting that feeding margarine with higher TFA levels may represent a direct source of oxidative stress for the organism. The present study provides evidence for a direct effect of TFA on NAFLD. PMID:21943357

Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats.

PubMed

Longhi, Rafael; Almeida, Roberto Farina; Machado, Letiane; Duarte, Maria Marta Medeiros Frescura; Souza, Débora Guerini; Machado, Priscila; de Assis, Adriano Martimbianco; Quincozes-Santos, André; Souza, Diogo Onofre

2017-04-01

Recent data regarding trans fatty acids (TFAs) have implicated these lipids as particularly deleterious to human health, causing systemic inflammation, endothelial dysfunction and possibly inflammation in the central nervous system (CNS). We aimed to clarify the impact of partially hydrogenated soybean oil (PHSO) with different TFA concentrations on cerebrospinal fluid (CSF), serum and hepatic parameters in adult Wistar rats. Wistar rats (n = 15/group) were fed either a normolipidic diet or a hyperlipidic diet for 90 days. The normolipidic and hyperlipidic diets had the same ingredients except for fat compositions, concentrations and calories. We used lard in the cis fatty acid group and PHSO in the trans fatty acid group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO) and (4) high partially hydrogenated soybean oil (HPHSO). Body weight, lipid profiles and the inflammatory responses in the CSF, serum and liver tissue were analyzed. Surprisingly, with the PHSO diet we observed a worse metabolic response that was associated with oxidative stress in hepatic tissue as well as impaired serum and CSF fluid parameters at both PHSO concentrations. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. Dietary supplementation with PHSO impaired inflammatory parameters in CSF and blood, induced insulin resistance, altered lipid profiles and caused hepatic damage. Overall, these findings suggest that fat composition is more important than the quantity of fat consumed in terms of cis and trans fatty acid diets.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ying; Li, Cuiying; Weng, Dong

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentagemore » of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung inflammation and fibrosis.« less

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion.

PubMed

Quartu, Marina; Serra, Maria P; Boi, Marianna; Pillolla, Giuliano; Melis, Tiziana; Poddighe, Laura; Del Fiacco, Marina; Falconieri, Danilo; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Piras, Antonio; Collu, Maria; Banni, Sebastiano

2012-01-12

Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

PubMed Central

2012-01-01

Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury. PMID:22239952

Investigations of kanuka and manuka essential oils for in vitro treatment of disease and cellular inflammation caused by infectious microorganisms.

PubMed

Chen, Chien-Chia; Yan, Sui-Hing; Yen, Muh-Yong; Wu, Pei-Fang; Liao, Wei-Ting; Huang, Tsi-Shu; Wen, Zhi-Hong; David Wang, Hui-Min

2016-02-01

Diseases caused by infectious and inflammatory microorganisms are among the most common and most severe nosocomial diseases worldwide. Therefore, developing effective agents for treating these illnesses is critical. In this study, essential oils from two tea tree species, kanuka (Kunzea ericoides) and manuka (Leptospermum scoparium), were evaluated for use in treating diseases and inflammation caused by microorganism infection. Isolates of clinically common bacteria and fungi were obtained from American Type Culture Collection and from Kaohsiung Veterans General Hospital. Minimum inhibitory concentrations for Trichosporon mucoides, Malassezia furfur, Candida albicans, and Candida tropicalis were determined by the broth microdilution method with Sabouraud dextrose broth. The antibacterial susceptibility of Staphylococcus aureus, Streptococcus sobrinus, Streptococcus mutans, and Escherichia coli were determined by the broth microdilution method. A human acute monocytic leukemia cell line (THP-1) was cultured to test the effects of the essential oils on the release of the two inflammatory cytokines, tumor necrosis factor-α and interleukin-4. Multiple analyses of microorganism growth confirmed that both essential oils significantly inhibited four fungi and the four bacteria. The potent fungicidal properties of the oils were confirmed by minimum inhibitory concentrations ranging from 0.78% to 3.13%. The oils also showed excellent bactericidal qualities with 100% inhibition of the examined bacteria. In THP-1 cells, both oils lowered tumor necrosis factor-α released after lipopolysaccharide stimulation. Finally, the antimicrobial and anti-inflammatory effects of the oils were obtained without adversely affecting the immune system. These results indicate that the potent antimicroorganism and anti-inflammation properties of kanuka and manuka essential oils make them strong candidates for use in treating infections and immune-related disease. The data confirm the potential use of kanuka and manuka extracts as pharmaceutical antibiotics, medical cosmetology agents, and food supplements. Copyright © 2014. Published by Elsevier B.V.

In vivo antinociceptive and anti-inflammatory activities of dried and fermented processed virgin coconut oil.

PubMed

Zakaria, Z A; Somchit, M N; Mat Jais, A M; Teh, L K; Salleh, M Z; Long, K

2011-01-01

The present study was carried out to investigate the antinociceptive and anti-inflammatory activities of virgin coconut oil (VCO) produced by the Malaysian Agriculture Research and Development Institute (MARDI) using various in vivo models. Two types of VCOs, produced via standard drying (VCOA) and fermentation (VCOB) processes were used in this study. Both VCOA and VCOB were serially diluted using 1% Tween 80 to concentrations (v/v) of 10, 50 and 100%. Antinociceptive and anti- inflammatory activities of both VCOs were examined using various in vivo model systems. The antinociceptive activity of the VCOs were compared to those of 1% Tween 80 (used as a negative control), morphine (5 mg/kg) and/or acetylsalicylic acid (100 mg/kg). Both VCOA and VCOB exhibited significant (p < 0.05) dose-dependent antinociceptive activity in the acetic acid-induced writhing test. Both VCOs also exerted significant (p < 0.05) antinociceptive activity in both phases of the formalin and hot-plate tests. Interestingly, the VCOs exhibited anti-inflammatory activity in an acute (carrageenan-induced paw edema test), but not in a chronic (cotton-pellet-induced granuloma test) model of inflammation. The MARDI-produced VCOs possessed antinociceptive and anti-inflammatory activities. Further studies are needed to confirm these observations. Copyright © 2011 S. Karger AG, Basel.

Preparation of coffee oil-algae oil-based nanoemulsions and the study of their inhibition effect on UVA-induced skin damage in mice and melanoma cell growth.

PubMed

Yang, Chu-Ching; Hung, Chi-Feng; Chen, Bing-Huei

2017-01-01

Coffee grounds, a waste by-product generated after making coffee, contains approximately 15% coffee oil which can be used as a raw material in cosmetics. Algae oil rich in docosahexaenoic acid (DHA) has been demonstrated to possess anticancer and anti-inflammation functions. The objectives of this study were to develop a gas chromatography-mass spectrometry (GC-MS) method for the determination of fatty acids in coffee oil and algae oil and prepare a nanoemulsion for studying its inhibition effect on ultraviolet A-induced skin damage in mice and growth of melanoma cells B16-F10. A total of 8 and 5 fatty acids were separated and quantified in coffee oil and algae oil by GC-MS, respectively, with linoleic acid (39.8%) dominating in the former and DHA (33.9%) in the latter. A nanoemulsion with a particle size of 30 nm, zeta potential -72.72 mV, and DHA encapsulation efficiency 100% was prepared by using coffee oil, algae oil, surfactant (20% Span 80 and 80% Tween 80), and deionized water. Differential scanning calorimetry (DSC) analysis revealed a high stability of nanoemulsion when heated up to 110°C at a pH 6, whereas no significant changes in particle size distribution and pH occurred over a 90-day storage period at 4°C. Animal experiments showed that a dose of 0.1% coffee oil-algae oil nanoemulsion was effective in mitigating trans-epidermal water loss, skin erythema, melanin formation, and subcutaneous blood flow. Cytotoxicity test implied effective inhibition of melanoma cell growth by nanoemulsion with an IC 50 value of 26.5 µg/mL and the cell cycle arrested at G2/M phase. A dose-dependent upregulation of p53, p21, cyclin B, and cyclin A expressions and downregulation of CDK1 and CDK2 occurred. Also, both Bax and cytochrome c expressions were upregulated and bcl-2 expression downregulated, accompanied by a rise in caspase-3, caspase-8, and caspase-9 activities for apoptosis execution. Collectively, the apoptosis pathway of melanoma cells B16-F10 may involve both mitochondria and death receptor.

Preparation of coffee oil-algae oil-based nanoemulsions and the study of their inhibition effect on UVA-induced skin damage in mice and melanoma cell growth

PubMed Central

Chen, Bing-Huei

2017-01-01

Coffee grounds, a waste by-product generated after making coffee, contains approximately 15% coffee oil which can be used as a raw material in cosmetics. Algae oil rich in docosahexaenoic acid (DHA) has been demonstrated to possess anticancer and anti-inflammation functions. The objectives of this study were to develop a gas chromatography-mass spectrometry (GC-MS) method for the determination of fatty acids in coffee oil and algae oil and prepare a nanoemulsion for studying its inhibition effect on ultraviolet A-induced skin damage in mice and growth of melanoma cells B16-F10. A total of 8 and 5 fatty acids were separated and quantified in coffee oil and algae oil by GC-MS, respectively, with linoleic acid (39.8%) dominating in the former and DHA (33.9%) in the latter. A nanoemulsion with a particle size of 30 nm, zeta potential −72.72 mV, and DHA encapsulation efficiency 100% was prepared by using coffee oil, algae oil, surfactant (20% Span 80 and 80% Tween 80), and deionized water. Differential scanning calorimetry (DSC) analysis revealed a high stability of nanoemulsion when heated up to 110°C at a pH 6, whereas no significant changes in particle size distribution and pH occurred over a 90-day storage period at 4°C. Animal experiments showed that a dose of 0.1% coffee oil-algae oil nanoemulsion was effective in mitigating trans-epidermal water loss, skin erythema, melanin formation, and subcutaneous blood flow. Cytotoxicity test implied effective inhibition of melanoma cell growth by nanoemulsion with an IC50 value of 26.5 µg/mL and the cell cycle arrested at G2/M phase. A dose-dependent upregulation of p53, p21, cyclin B, and cyclin A expressions and downregulation of CDK1 and CDK2 occurred. Also, both Bax and cytochrome c expressions were upregulated and bcl-2 expression downregulated, accompanied by a rise in caspase-3, caspase-8, and caspase-9 activities for apoptosis execution. Collectively, the apoptosis pathway of melanoma cells B16-F10 may involve both mitochondria and death receptor. PMID:28919754

An increase in liver PPARγ2 is an initial event to induce fatty liver in response to a diet high in butter: PPARγ2 knockdown improves fatty liver induced by high-saturated fat.

PubMed

Yamazaki, Tomomi; Shiraishi, Sayaka; Kishimoto, Kyoko; Miura, Shinji; Ezaki, Osamu

2011-06-01

The effects of a diet rich in saturated fat on fatty liver formation and the related mechanisms that induce fatty liver were examined. C57BL/6J mice were fed butter or safflower oil as a high-fat (HF) diet (40% fat calories) for 2, 4, 10, or 17 weeks. Although both HF diets induced similar levels of obesity, HF butter-fed mice showed a two to threefold increase in liver triacylglycerol (TG) concentration compared to HF safflower oil-fed mice at 4 or 10 weeks without hyperinsulinemia. At 4 weeks, increases in peroxisome proliferator-activated receptor γ2 (PPARγ2), CD36, and adipose differentiation-related protein (ADRP) mRNAs were observed in HF butter-fed mice; at 10 weeks, an increase in sterol regulatory element-binding protein-1c (SREBP-1c) was observed; at 17 weeks, these increases were attenuated. At 4 weeks, a single injection of adenoviral vector-based short hairpin interfering RNA against PPARγ2 in HF butter-fed mice reduced PPARγ protein and mRNA of its target genes (CD36 and ADRP) by 43%, 43%, and 39%, respectively, with a reduction in liver TG concentration by 38% in 5 days. PPARγ2 knockdown also reduced mRNAs in lipogenic genes (fatty-acid-synthase, stearoyl-CoA desaturase 1, acetyl-CoA carboxylase 1) without alteration of SREBP-1c mRNA. PPARγ2 knockdown reduced mRNAs in genes related to inflammation (CD68, interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1). In conclusion, saturated fatty acid-rich oil induced fatty liver in mice, and this was triggered initially by an increase in PPARγ2 protein in the liver, which led to increased expression of lipogenic genes. Inactivation of PPARγ2 may improve fatty liver induced by HF saturated fat. Copyright © 2011 Elsevier Inc. All rights reserved.

Autoimmune/inflammatory syndrome induced by mineral oil: a health problem.

PubMed

Vera-Lastra, Olga; Medina, Gabriela; Cruz-Domínguez, María Pilar; Ramírez, Gabriel Medrano; Blancas, Raymundo Benjamin Priego; Amaro, Ana Lilia Peralta; Martínez, Anabel Villanueva; Delgado, Jesús Sepúlveda; Jara, Luis J

2018-06-01

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.

What causes high fat diet-induced postprandial inflammation: endotoxin or free fatty acids?

USDA-ARS?s Scientific Manuscript database

Introduction High fat (saturated fat) diet has been generally used to induce tissue inflammation, insulin resistance and obesity in animal models. High fat diet can also induce postprandial inflammation in humans. Importantly, postprandial inflammation is linked to elevated cardiovascular and metabo...

[Chemical peels and management of skin aging].

PubMed

Pelletier-Louis, M-L

2017-10-01

Chemical peels are an alternative and/or a complementary treatment to the surgical procedures for skin aging. The purpose of this article is to specify the procedures and the indications of the three principal types of chemical peels: alpha-hydroxy acids, trichloracetic acid, phenol-croton oil peel. The clinical examination will determine the depth of the lesions to treat and will take into consideration counter-indications and specific limits to each patient. Chemical peel is a four step procedure: pre-peel preparation, peeling itself, recovery phase and maintenance phase. The preparation is a very important phase which requires a thorough knowledge of cosmetics. This preparation can extend to any medical or surgical treatment for aging skin. Various techniques of peelings: superficial, medium, deep, combined and mosaïc peel will be detailed. These procedures require a rigorous training and a distinct learning curve. The follow up will be specified as well as the management of the possible complications. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Inflammatory ointment from shea butter and hydro-alcoholic extract of Khaya senegalensis barks (Cailcederat)].

PubMed

Thioune, O; Ahodikpe, D; Dieng, M; Diop, A B; Ngom, S; Lo, I

2000-01-01

In a former study, it was proved that the alcoholic solution of hydro-alcoholic extract of Khaya senegalensis barks had an anti-inflammatory activity on animals after a local application. In this work, ointments made from the same extract and three different excipients (vaseline, lanoline and shea butter (crude and refined)) have been prepared and tested by the method of the croton oil inhibited ear oedema. Results showed inhibition percentages of the ear oedema of 58.8%, 66.7% and 75.4% when the hydro-alcoholic extract was tested at respective doses of 1%, 2% and 3% in shea butter. The two other excipients, (vaceline and Lanoline) tested at the dose of 3% showed between 52% and 58% of inhibitions. The interest of this study was to demonstrate the possibility to maintain the anti-inflammatory activity of Khaya senegalensis barks by using them in a galenic form, easy to prepare and which is, in addition, more adapted than the extract to possible clinical trials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Yuan; Zhao, Yue; Xu, Wenchao

Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover,more » IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α. • Inflammation is involved in arsenite-induced carcinogenesis.« less

Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N.

PubMed

Badreddine, Asmaa; Zarrouk, Amira; Karym, El Mostafa; Debbabi, Meryam; Nury, Thomas; Meddeb, Wiem; Sghaier, Randa; Bezine, Maryem; Vejux, Anne; Martine, Lucy; Grégoire, Stéphane; Bretillon, Lionel; Prost-Camus, Emmanuelle; Durand, Philippe; Prost, Michel; Moreau, Thibault; Cherkaoui-Malki, Mustapha; Nasser, Boubker; Lizard, Gérard

2017-10-23

Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25-50 µM; 24 h) without and with argan oil (0.1% v / v ) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.

Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N

PubMed Central

Badreddine, Asmaa; Zarrouk, Amira; Karym, El Mostafa; Debbabi, Meryam; Nury, Thomas; Meddeb, Wiem; Sghaier, Randa; Bezine, Maryem; Martine, Lucy; Grégoire, Stéphane; Bretillon, Lionel; Durand, Philippe; Prost, Michel; Moreau, Thibault; Cherkaoui-Malki, Mustapha; Nasser, Boubker

2017-01-01

Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25–50 µM; 24 h) without and with argan oil (0.1% v/v) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier. PMID:29065513

Water-soluble phenol TS-13 combats acute but not chronic inflammation.

PubMed

Menshchikova, Elena; Tkachev, Victor; Lemza, Anna; Sharkova, Tatyana; Kandalintseva, Natalya; Vavilin, Valentin; Safronova, Olga; Zenkov, Nikolay

2014-09-01

This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation. Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis. The effects of TS-13 treatment were estimated by changes in the intensity of inflammation (paw edema, liver infiltration, animal survival, exudation, and clinical score of arthritis) and by the effects on reactive oxygen species (ROS) generation by leukocytes from peripheral blood and inflammatory exudates. We found the significant increase in expression of mRNA, content of protein and activity of a well-characterized Nrf2 target enzyme glutathione S-transferase P1, as well as nuclear extract protein binding to the ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13 markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte number and volume density of liver infiltrates in the systemic zymosan-induced inflammation model, and increased mice survival after lipopolysaccharide-induced septic shock. However, TS-13 administration did not influence cell and protein exudation into air pouches and suppressed clinical manifestation of collagen-induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the generation of ROS by leukocytes in all inflammation models. The data suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more prominent against acute innate-mediated inflammation than chronic immune inflammation. This narrows the potential therapeutic efficacy of ARE inducers in inflammation treatment.

Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats.

PubMed

Chen, J; Winston, J H; Sarna, S K

2013-09-17

The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats

PubMed Central

Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei

2013-01-01

Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. PMID:24113767

Therapeutic effect of umbelliferon-α-D-glucopyranosyl-(2(I)→1(II))-α-D-glucopyranoside on adjuvant-induced arthritic rats.

PubMed

Kumar, Vikas; Anwar, Firoz; Verma, Amita; Mujeeb, Mohd

2015-06-01

The aim and objective of the present investigation was to evaluate the antiarthritic and antioxidant effect of umbelliferon-α-D-glucopyranosyl-(2I→1II)-α-D-glucopyranoside (UFD) in chemically induced arthritic rats. The different doses of the UFD were tested against the turpentine oil (TO), formaldehyde induced acute arthritis and complete fruend's adjuvant (CFA) induced chronic arthritis in Wistar rats. Arthritic assessment and body weight was measured at regular interval till 28 days. On day 28, all the groups animals were anaesthetized, blood were collected from the puncturing the ratro orbital and estimated the hematological parameters. The animals were sacrificed; synovial tissue was extracted and estimated the malonaldehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The different doses of the UFD showed the protective effect against turpentine oil, formaldehyde induced acute arthritis and CFA induced chronic arthritis at dose dependent manner. Acute model of arthritis such as TOand formaldehyde induced inflammation due to releasing of the inflammatory mediators; significantly inhibited by the UFD at dose dependent manner. CFA induced arthritic rats treated with the different doses of the UFD showed the inhibitory effect on the delayed increase in joint diameter as seen in arthritic control group rats. UFD significantly improved the arthritic index, body weight and confirmed the antiarthritic effect. UFD showed the effect on the hematological parameter such as improved the level of the RBC, Hb and decline the level of the EBC, ESR and confirmed the immune suppressive effect. UFD significantly improved the level of the endogenous antioxidant and confirmed the antioxidant effect. This present investigation suggests that the UFD has prominent antiarthritic impact which can be endorsed to its antiarthritic and antioxidant effects.

Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery.

PubMed

Bermúdez, Beatriz; López, Sergio; Pacheco, Yolanda M; Villar, José; Muriana, Francisco J G; Hoheisel, Jöerg D; Bauer, Andrea; Abia, Rocío

2008-07-15

Postprandial triglyceride-rich lipoproteins (TRL) have a direct effect on vascular smooth muscle cells (SMC) and they increase the risk of atherogenesis. Here, we have tested the hypothesis that the different fatty acid composition of TRL is capable of differentially modifying gene expression in human coronary artery SMC (CASMC). In addition, the effect of TRL on cell proliferation and transcription factor activation was also evaluated. TRL were prepared from plasma of healthy volunteers after the ingestion of meals enriched in refined olive oil (ROO), butter or a mixture of vegetable and fish oils (VEFO). We use cDNA microarrays to determine the genes differentially expressed in TRL-treated CASMC. Correspondence cluster analysis demonstrated that TRL-butter, -ROO and -VEFO provoked different transcriptional profiles in CASMC. Sixty-six genes were regulated by TRL-butter, 55 by -ROO, and 47 by -VEFO. The data revealed that TRL-butter predominantly activated genes involved in the regulation of cell proliferation and inflammation. Likewise, TRL-VEFO induced the expression of genes implicated in inflammation, while TRL-ROO promoted a less atherogenic gene profile. The pathophysiological contribution of TRL to the development of atherosclerosis and the stability of atherosclerotic plaques may depend on the fatty acid composition of TRL. Our findings suggest a role for macrophage-inhibiting cytokine-1 (MIC-1) in coronary artery cardiovascular events.

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia.

PubMed

Shirai, Yumiko; Okugawa, Yoshinaga; Hishida, Asahi; Ogawa, Aki; Okamoto, Kyoko; Shintani, Miki; Morimoto, Yuki; Nishikawa, Ryutaro; Yokoe, Takeshi; Tanaka, Koji; Urata, Hisashi; Toiyama, Yuji; Inoue, Yasuhiro; Tanaka, Motoyoshi; Mohri, Yasuhiko; Goel, Ajay; Kusunoki, Masato; McMillan, Donald C; Miki, Chikao

2017-07-06

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

Cyclohexanecarboxyl-Coenzyme A (CoA) and Cyclohex-1-ene-1-Carboxyl-CoA Dehydrogenases, Two Enzymes Involved in the Fermentation of Benzoate and Crotonate in Syntrophus aciditrophicus

PubMed Central

Kung, Johannes W.; Seifert, Jana; von Bergen, Martin

2013-01-01

The strictly anaerobic Syntrophus aciditrophicus is a fermenting deltaproteobacterium that is able to degrade benzoate or crotonate in the presence and in the absence of a hydrogen-consuming partner. During growth in pure culture, both substrates are dismutated to acetate and cyclohexane carboxylate. In this work, the unknown enzymes involved in the late steps of cyclohexane carboxylate formation were studied. Using enzyme assays monitoring the oxidative direction, a cyclohex-1-ene-1-carboxyl-CoA (Ch1CoA)-forming cyclohexanecarboxyl-CoA (ChCoA) dehydrogenase was purified and characterized from S. aciditrophicus and after heterologous expression of its gene in Escherichia coli. In addition, a cyclohexa-1,5-diene-1-carboxyl-CoA (Ch1,5CoA)-forming Ch1CoA dehydrogenase was characterized after purification of the heterologously expressed gene. Both enzymes had a native molecular mass of 150 kDa and were composed of a single, 40- to 45-kDa subunit; both contained flavin adenine dinucleotide (FAD) as a cofactor. While the ChCoA dehydrogenase was competitively inhibited by Ch1CoA in the oxidative direction, Ch1CoA dehydrogenase further converted the product Ch1,5CoA to benzoyl-CoA. The results obtained suggest that Ch1,5CoA is a common intermediate in benzoate and crotonate fermentation that serves as an electron-accepting substrate for the two consecutively operating acyl-CoA dehydrogenases characterized in this work. In the case of benzoate fermentation, Ch1,5CoA is formed by a class II benzoyl-CoA reductase; in the case of crotonate fermentation, Ch1,5CoA is formed by reversing the reactions of the benzoyl-CoA degradation pathway that are also employed during the oxidative (degradative) branch of benzoate fermentation. PMID:23667239

The xanthine oxidase inhibitor Febuxostat reduces tissue uric acid content and inhibits injury-induced inflammation in the liver and lung

PubMed Central

Kataoka, Hiroshi; Yang, Ke; Rock, Kenneth L.

2014-01-01

Necrotic cell death in vivo induces a robust neutrophilic inflammatory response and the resulting inflammation can cause further tissue damage and disease. Dying cells induce this inflammation by releasing pro-inflammatory intracellular components, one of which is uric acid. Cells contain high levels of intracellular uric acid, which is produced when purines are oxidized by the enzyme xanthine oxidase. Here we test whether a non-nucleoside xanthine oxidase inhibitor, Febuxostat (FBX), can reduce intracellular uric acid levels and inhibit cell death-induced inflammation in two different murine tissue injury models; acid-induced acute lung injury and acetaminophen liver injury. Infiltration of inflammatory cells induced by acid injection into lungs or peritoneal administration of acetaminophen was evaluated by quantification with flow cytometry and tissue myeloperoxidase activity in the presence or absence of FBX treatment. Uric acid levels in serum and tissue were measured before giving the stimuli and during inflammation. The impact of FBX treatment on the peritoneal inflammation caused by the microbial stimulus, zymosan, was also analyzed to see whether FBX had a broad anti-inflammatory effect. We found that FBX reduced uric acid levels in acid-injured lung tissue and inhibited acute pulmonary inflammation triggered by lung injury. Similarly, FBX reduced uric acid levels in the liver and inhibited inflammation in response to acetaminophen-induced hepatic injury. In contrast, FBX did not reduce inflammation to zymosan, and therefore is not acting as a general anti-inflammatory agent. These results point to the potential of using agents like FBX to treat cell death-induced inflammation. PMID:25449036

Comparative Effects of Two Gingerol-Containing Zingiber officinale Extracts on Experimental Rheumatoid Arthritis1

PubMed Central

Funk, Janet L.; Frye, Jennifer B.; Oyarzo, Janice N.; Timmermann, Barbara N.

2009-01-01

Ginger (Zingiber officinale) supplements are being promoted for arthritis treatment in western societies based on ginger’s traditional use as an anti-inflammatory in Chinese and Ayurvedic medicine. However, scientific evidence of ginger’s antiarthritic effects is sparse, and its bioactive joint-protective components have not been identified. Therefore, the ability of a well-characterized crude ginger extract to inhibit joint swelling in an animal model of rheumatoid arthritis, streptococcal cell wall (SCW)-induced arthritis, was compared to that of a fraction containing only gingerols and their derivatives. Both extracts were efficacious in preventing joint inflammation. However, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content) in preventing both joint inflammation and destruction. In conclusion, these data document a very significant joint-protective effect of these ginger samples, and suggest that non-gingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols. PMID:19216559

Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways.

PubMed

Chen, Kung-Yen; Lin, Jui-An; Yao, Han-Yun; Hsu, An-Chih; Tai, Yu-Ting; Chen, Jui-Tai; Hsieh, Mao-Chih; Shen, Tang-Long; Hsu, Ren-Yi; Wu, Hong-Tan; Wang, Guey Horng; Ho, Bing-Ying; Chen, Yu-Pei

2018-04-01

Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1β, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Asymmetric conjugate 1,4-addition of arylboronic acids to alpha, beta-unsaturated esters catalyzed by Rhodium(I)/(S)-binap

PubMed

Sakuma; Sakai; Itooka; Miyaura

2000-09-22

Arylboronic acids underwent the conjugate 1,4-addition to alpha, beta-unsaturated esters to give beta-aryl esters in high yields in the presence of a rhodium(I) catalyst. The addition of arylboronic acids to isopropyl crotonate resulted in high yields and high enantioselectivity exceeding 90% ee in the presence of 3 mol % of Rh(acac)(C(2)H(4))(2) and (S)-binap at 100 degrees C. The rhodium/(S)-binap complex provided (R)-3-phenylbutanoate in the addition of phenylboronic acid to benzyl crotonate. The effects on the enantioselectivity of chiral phosphine ligands, rhodium precursors, and substituents on alpha,beta-unsaturated esters are discussed, as well as the mechanistic aspect of the catalytic cycle.

Healthy effect of different proportions of marine ω-3 PUFAs EPA and DHA supplementation in Wistar rats: Lipidomic biomarkers of oxidative stress and inflammation.

PubMed

Dasilva, Gabriel; Pazos, Manuel; García-Egido, Eduardo; Gallardo, Jose Manuel; Rodríguez, Isaac; Cela, Rafael; Medina, Isabel

2015-11-01

Dietary intervention with ω-3 marine fatty acids may potentially modulate inflammation and oxidative stress markers related with CVD, metabolic syndrome and cancer. The aim of this study was to evaluate whether different proportions of ω-3 EPA and DHA intake provoke a modulation of the production of lipid mediators and then, an influence on different indexes of inflammation and oxidative stress in a controlled dietary animal experiment using Wistar rats. For such scope, a lipidomic SPE-LC-ESI-MS/MS approach previously developed was applied to determine lipid mediators profile in plasma samples. The effect of ω-3 fatty acids associated to different ratios EPA:DHA was compared with the effect exerted by ω-3 ALA supplementation from linseed oil and ω-6 LA from soybean oil. CRP showed a tendency to greater inflammatory status in all ω-3-fed animals. Interestingly, ratios 1:1 and 2:1 EPA:DHA evidenced a noteworthy healthy effect generating a less oxidative environment and modulating LOX and COX activities toward a decrease in the production of proinflammatory ARA eicosanoids and oxidative stress biomarkers from EPA and DHA. In addition, the ability of 1:1 and 2:1 fish oil diets to reduce lipid mediator levels was in concurrence with the protective effect exerted by decreasing inflammatory markers as ω-6/ω-3 ratio in plasma and membranes. It was also highlighted the effect of a higher DHA amount in the diet reducing the healthy benefits described in terms of inflammation and oxidative stress. Results support the antiinflammatory and antioxidative role of fish oils and, particularly, the effect of adequate proportions EPA:DHA. Copyright © 2015 Elsevier Inc. All rights reserved.

Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway.

PubMed

Zhang, Zhiguo; Wang, Shudong; Zhou, Shanshan; Yan, Xiaoqing; Wang, Yonggang; Chen, Jing; Mellen, Nicholas; Kong, Maiying; Gu, Junlian; Tan, Yi; Zheng, Yang; Cai, Lu

2014-12-01

Type 2 diabetes mellitus (T2DM)-induced cardiomyopathy is associated with cardiac oxidative stress, inflammation, and remodeling. Sulforaphane (SFN), an isothiocyanate naturally presenting in widely consumed vegetables, particularly broccoli, plays an important role in cardiac protection from diabetes. We investigated the effect of SFN on T2DM-induced cardiac lipid accumulation and subsequent cardiomyopathy. Male C57BL/6J mice were fed a high-fat diet for 3months to induce insulin resistance, followed by a treatment with 100mg/kg body-weight streptozotocin to induce hyperglycemia; we referred to it as the T2DM mouse model. Other age-matched mice were fed a normal diet as control. T2DM and control mice were treated with or without 4-month SFN at 0.5mg/kg daily five days a week. At the study's end, cardiac function was assessed. SFN treatment significantly attenuated cardiac remodeling and dysfunction induced by T2DM. SFN treatment also significantly inhibited cardiac lipid accumulation, measured by Oil Red O staining, and improved cardiac inflammation oxidative stress and fibrosis, shown by down-regulating diabetes-induced PAI-1, TNF-α, CTGF, TGF-β, 3-NT, and 4-HNE expression. Elevated 4-HNE resulted in the increase of 4-HNE-LKB1 adducts that should inhibit LKB1 and subsequent AMPK activity. SFN upregulated the expression of Nrf2 and its downstream genes, NQO1 and HO-1, decreased 4-HNE-LKB1 adducts and then reversed diabetes-induced inhibition of LKB1/AMPK and its downstream targets, including sirtuin 1, PGC-1α, phosphorylated acetyl-CoA carboxylase, carnitine palmitoyl transferase-1, ULK1, and light chain-3 II. These results suggest that SFN treatment to T2DM mice may attenuate the cardiac oxidative stress-induced inhibition of LKB1/AMPK signaling pathway, thereby preventing T2DM-induced lipotoxicity and cardiomyopathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Echium oil compared with marine oils on lipid profile and inhibition of hepatic steatosis in LDLr knockout mice

PubMed Central

2013-01-01

Background In an effort to identify new alternatives for long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) supplementation, the effect of three sources of omega 3 fatty acids (algae, fish and Echium oils) on lipid profile and inflammation biomarkers was evaluated in LDL receptor knockout mice. Methods The animals received a high fat diet and were supplemented by gavage with an emulsion containing water (CON), docosahexaenoic acid (DHA, 42.89%) from algae oil (ALG), eicosapentaenoic acid (EPA, 19.97%) plus DHA (11.51%) from fish oil (FIS), and alpha-linolenic acid (ALA, 26.75%) plus stearidonic acid (SDA, 11.13%) from Echium oil (ECH) for 4 weeks. Results Animals supplemented with Echium oil presented lower cholesterol total and triacylglycerol concentrations than control group (CON) and lower VLDL than all of the other groups, constituting the best lipoprotein profile observed in our study. Moreover, the Echium oil attenuated the hepatic steatosis caused by the high fat diet. However, in contrast to the marine oils, Echium oil did not affect the levels of transcription factors involved in lipid metabolism, such as Peroxisome Proliferator Activated Receptor α (PPAR α) and Liver X Receptor α (LXR α), suggesting that it exerts its beneficial effects by a mechanism other than those observed to EPA and DHA. Echium oil also reduced N-6/N-3 FA ratio in hepatic tissue, which can have been responsible for the attenuation of steatosis hepatic observed in ECH group. None of the supplemented oils reduced the inflammation biomarkers. Conclusion Our results suggest that Echium oil represents an alternative as natural ingredient to be applied in functional foods to reduce cardiovascular disease risk factors. PMID:23510369

Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis.

PubMed

Al-Gayyar, Mohammed M H; Hassan, Hanan M; Alyoussef, Abdullah; Abbas, Ahmed; Darweish, Mohamed M; El-Hawwary, Amany A

2016-03-01

Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). Seventy adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.

Soybean and Fish Oil Mixture With Different ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium-Induced Changes in Small Intestinal Intraepithelial γδT-Lymphocyte Expression in Mice.

PubMed

Pai, Man-Hui; Liu, Jun-Jen; Hou, Yu-Chen; Yeh, Chiu-Li

2016-03-01

This study investigated the effect of different ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)-induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT-cell expression. Mice were assigned to 3 control and 3 DSS-treated groups and were maintained on a low-fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω-3 and Lω-3) groups and 2 other DSS (DHω-3 and DLω-3) groups were fed either a soybean and fish oil mixture with a ω-6/ω-3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT-cell subset was isolated for analysis. DSS treatment resulted in a lower small intestinal IEL γδT-cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω-3 group, the DHω-3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator-activated receptor (PPAR)-γ gene by small intestinal IEL γδT cells. Fish oil diets with a ω-6/ω-3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS-induced small intestinal injury, and activation of PPAR-γ in IEL γδT cells may be associated with resolution of small intestinal inflammation. © 2014 American Society for Parenteral and Enteral Nutrition.

Effects of fish and krill oil on gene expression in peripheral blood mononuclear cells and circulating markers of inflammation: a randomised controlled trial.

PubMed

Rundblad, Amanda; Holven, Kirsten B; Bruheim, Inge; Myhrstad, Mari C; Ulven, Stine M

2018-01-01

Marine n -3 (omega-3) fatty acids alter gene expression by regulating the activity of transcription factors. Krill oil is a source of marine n -3 fatty acids that has been shown to modulate gene expression in animal studies; however, the effect in humans is not known. Hence, we aimed to compare the effect of intake of krill oil, lean and fatty fish with a similar content of n -3 fatty acids, and high-oleic sunflower oil (HOSO) with added astaxanthin on the expression of genes involved in glucose and lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC) as well as circulating inflammatory markers. In an 8-week trial, healthy men and women aged 18-70 years with fasting TAG of 1·3-4·0 mmol/l were randomised to receive krill oil capsules ( n 12), HOSO capsules ( n 12) or lean and fatty fish ( n 12). The weekly intakes of marine n -3 fatty acids from the interventions were 4654, 0 and 4103 mg, respectively. The mRNA expression of four genes, PPAR γ coactivator 1A ( PPARGC1A ), steaoryl-CoA desaturase ( SCD ), ATP binding cassette A1 ( ABCA1 ) and cluster of differentiation 40 ( CD40 ), were differently altered by the interventions. Furthermore, within-group analyses revealed that krill oil down-regulated the mRNA expression of thirteen genes, including genes involved in glucose and cholesterol metabolism and β-oxidation. Fish altered the mRNA expression of four genes and HOSO down-regulated sixteen genes, including several inflammation-related genes. There were no differences between the groups in circulating inflammatory markers after the intervention. In conclusion, the intake of krill oil and HOSO with added astaxanthin alter the PBMC mRNA expression of more genes than the intake of fish.

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw

PubMed Central

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-01-01

Background and purpose: α-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of α-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. Experimental approach: The biological activities of α-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-κB and up-regulated expression of kinin B1 receptors. Key results: Treatment with either α-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-κB induced by LPS in the rat paw. However, only α-humulene significantly reduced the increase in TNF-α and IL-1β levels, paw oedema and the up-regulation of B1 receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Conclusions and Implications: Both α-humulene and trans-caryophyllene inhibit the LPS-induced NF-κB activation and neutrophil migration, although only α-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-α and IL-1β and the in vivo up-regulation of kinin B1 receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes α-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases. PMID:17471174

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw.

PubMed

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-07-01

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

PubMed Central

Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Torres, Larissa Helena Lobo; Durão, Ana Carolina Cardoso Santos; Shimada, Ana Lucia Borges; Almeida, Francine Maria; Hebeda, Cristina Bichels; Lopes, Fernanda Degobbi Tenorio Quirino Santos; Dolhnikoff, Marisa; Martins, Milton Arruda; Silva, Luiz Fernando Ferraz; Farsky, Sandra Helena Poliselli; Saldiva, Paulo Hilário Nascimento; Ulrich, Cornelia M.; Owen, Robert W.; Marcourakis, Tania; Trevisan, Maria Teresa Salles; Mauad, Thais

2013-01-01

Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50 μg of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100 μL of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs. PMID:23533495

Geraniol produces antidepressant-like effects in a chronic unpredictable mild stress mice model.

PubMed

Deng, Xue-Yang; Xue, Jin-Song; Li, Hong-Yan; Ma, Zhan-Qiang; Fu, Qiang; Qu, Rong; Ma, Shi-Ping

2015-12-01

Geraniol (GE), which has neuroprotection and anti-inflammation activities, is mostly abundant in the essential oils of rose, ginger, lemon, orange, lavender etc. However, its antidepressant-like effect has not been reported before. The present study was designed to investigate whether GE confers an antidepressant effect in mice exposed to a chronic unpredictable mild stress (CUMS) model of depression and to explore its possible mechanisms. The results showed that GE treatments for 3 weeks significantly alleviated the depression-related behaviors of CUMS-exposed mice, as indicated by restored decreased sucrose preference and shortened immobile time in both the forced swimming tests (FST) and tail suspension tests (TST). And these ameliorative effects of GE treatment were involved with regulating CUMS-induced pro-inflammatory cytokine interleukin-1 beta (IL-1β) related neuro-inflammation. We further found that GE treatment reversed CUMS-induced IL-1β elevation, possibly by inhibiting nuclear factor kappa B (NF-κB) pathway activation and regulating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome expression. Taken together, our findings suggested that GE exerted a potential antidepressant-like effect in CUMS mice model of depression, which may provide an insight into the potential of GE in therapeutic implications for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

Alcmaeon of Croton.

PubMed

Debernardi, Alberto; Sala, Elena; D'Aliberti, Giuseppe; Talamonti, Giuseppe; Franchini, Antonia Francesca; Collice, Massimo

2010-02-01

IN THE LATTER half of the sixth century BC, Croton was the site of the most famous medical school in Magna Graecia, where diseases of the human body were examined in a scientific and experimental manner instead of by using the contemporary supernatural, nearly magical concepts. Alcmaeon was one of the most active physicians interested in human physiology in the medical tradition of Croton. Although Alcmaeon was devoted to science and was a skillful experimentalist, little is known about his life and his exact birth date. The relative isolation of Alcmaeon from the great philosophical currents of his time probably facilitated his unprejudiced methodology and may have prevented him from disclosing his theories and demonstrating their value. He pioneered the concept of the relationship between the brain and the mind and was the first to identify the brain as the center of understanding and the essential organ for perceptions, sensations, and thoughts. Through systematic observations, Alcmaeon brought many things to light about the characteristics of the eye and the presence of channels connecting head sensory organs to the brain. He stated that the soul was immortal and introduced the tekmairesthai doctrine, through which the ideas of anamnesis and prognosis gave birth. We highlight his contributions to medical thought, and especially to neuroscience, which reveal Alcmaeon to be a thinker of considerable originality and one of the greatest philosophers, naturalists, and neuroscientists of all time.

Enzymatic and microstructural changes in the liver of experimental rats fed with fatty diet and fresh or heated soy oil concurrently.

PubMed

Jaarin, K; Hwa, Tay Chin; Umar, Nor Aini; Siti Aishah, M A; Das, S

2010-01-01

Consumption of heated edible oils may be harmful. The present study aimed to observe the histological changes due to concurrent consumption of soy oil (either fresh or heated) and fatty diet and the changes in the level of alanine transaminase (ALT) and alkaline phosphatase (ALP). Forty female Spraque-Dawley rats were equally divided into four groups (I to IV). All the rats n groups II, III and IV were ovariectomised. Rats in group I (control) were fed with 2% cholesterol diet, whereas the rats in groups II, III and IV were fed with 2% cholesterol diet fortified with 15% weight/weight (w/w) fresh soy oil (FSO), once heated soy oil (1HSO) and five times heated soy oil (5HSO) respectively, for 16 weeks. Blood was taken for liver enzymes and analysed before and after 16 weeks of study. At the end of the study the animals were sacrificed, and the liver was examined histologically. The specimens were weighed, formalin fixed and the sections were stained with hematoxylin and eosin. Fresh, 1HSO and 5HSO soy oil caused significant increase in serum ALT and ALP compared to their base line values. Fresh, 1HSO and 5HSO soy oil caused microsteatosis, inflammation and necrosis of the liver tissues. However, there was no significant difference in the ALT and ALP enzyme levels amongst the oil fed groups. It is concluded that the effect of both fresh and heated soy oil on these parameters was not affected by repeated heating except for the inflammation.

The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.

PubMed

Colinot, Darrelle L; Garbuz, Tamila; Bosland, Maarten C; Wang, Liang; Rice, Susan E; Sullivan, William J; Arrizabalaga, Gustavo; Jerde, Travis J

2017-07-01

Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia. © 2017 Wiley Periodicals, Inc.

The injury of fine particulate matter from cooking oil fumes on umbilical cord blood vessels in vitro.

PubMed

Hou, Lijuan; Zhang, Jian; Zhang, Chao; Xu, Yachun; Zhu, Xiaoxia; Yao, Cijiang; Liu, Ying; Li, Tao; Cao, Jiyu

2017-01-01

Cooking oil fumes (COFs) derived PM 2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM 2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM 2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM 2.5 resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM 2.5 . In conclusion, our data suggested that exposure to COFs-derived PM 2.5 resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Heat shock factor 1 suppresses the HIV-induced inflammatory response by inhibiting nuclear factor-κB.

PubMed

Pan, Xiaoyan; Lin, Jian; Zeng, Xiaoyun; Li, Wenjuan; Wu, Wenjiao; Lu, Wan Zhen; Liu, Jing; Liu, Shuwen

2018-05-01

The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4 + T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation. Mechanistically, HSF1 was found to compete with nuclear factor-κB (NF-κB) in the nucleus. Generally, our report highlights that HSF1 is an important host factor in regulating HIV-induced inflammation and may work as a potential target for curing AIDS. Copyright © 2018 Elsevier Inc. All rights reserved.

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

PubMed Central

Moran, Ana; Thacker, Stephen A.; Arikan, Ayse Akcan; Mastrangelo, Mary-Ann A.; Wu, Yong; Yu, Bi; Tweardy, David J.

2011-01-01

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome. PMID:21738667

Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

PubMed

Maessen, Dionne E; Brouwers, Olaf; Gaens, Katrien H; Wouters, Kristiaan; Cleutjens, Jack P; Janssen, Ben J; Miyata, Toshio; Stehouwer, Coen D; Schalkwijk, Casper G

2016-04-01

Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats.

PubMed

Abolaji, Amos O; Ojo, Mercy; Afolabi, Tosin T; Arowoogun, Mary D; Nwawolor, Darlinton; Farombi, Ebenezer O

2017-05-25

Chlorpyrifos (CPF) is an organophosphorus pesticide widely used in agricultural applications and household environments. 6-Gingerol-rich fraction from Zingiber officinale (Ginger, 6-GRF) has been reported to possess potent anti-oxidative, anti-inflammatory and anti-apoptotic properties. Here, we investigated the protective properties of 6-GRF on CPF-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Five groups of rats containing 14 rats/group received corn oil (control), CPF (5 mg/kg), 6-GRF (100 mg/kg), CPF (5 mg/kg) + 6-GRF (50 mg/kg) and CPF (5 mg/kg) + 6-GRF (100 mg/kg) through gavage once per day for 35 days respectively. The results showed that 6-GRF protected against CPF-induced increases in oxidative stress ((hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA)), inflammatory (myeloperoxidase (MPO), nitric oxide (NO) and tumour necrosis factor-α (TNF- α)), and apoptotic (caspase-3) markers. Also, 6-GRF improved the activities of antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) as well as glutathione (GSH) level in the brain, ovary and uterus of rats exposed to CPF (p < 0.05). Overall, the protective effects of 6-GRF on CPF-induced toxicity in the brain and reproductive organs of rats may be due to its potent antioxidative, anti-inflammatory and antiapoptotic properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Olives and Bone: A Green Osteoporosis Prevention Option

PubMed Central

Chin, Kok-Yong; Ima-Nirwana, Soelaiman

2016-01-01

Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly. PMID:27472350

Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Zhilin; Ukomadu, Chinweike

2008-01-25

Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is upregulated in regenerating rodent livers following partial hepatectomy. It has been implicated as a mitogen for liver cell proliferation. In this study, we show that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern similar to those of acute phase reactants. Following induction of acute inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1 levels are also enhanced. Although, a recent report suggests that FGL1 associates almost exclusively with the fibrin matrix, we report here that approximately 20% of the total plasma FGL1more » remains free. The enhancement of FGL1 levels in vitro by IL-6 and its induction after turpentine oil injection suggest that it is an acute phase reactant. Its presence in bound and free forms in the blood also implies biological roles that extend beyond the proposed autocrine effect it has on hepatocytes during regeneration.« less

Cycloartenyl ferulate, a component of rice bran oil-derived gamma-oryzanol, attenuates mast cell degranulation.

PubMed

Oka, T; Fujimoto, M; Nagasaka, R; Ushio, H; Hori, M; Ozaki, H

2010-02-01

IgE-targeting therapy could provide significant progress in the treatment of allergic inflammation. In this study, we examined the effect of cycloartenyl ferulate (cycloartenol ferulic acid ester; CAF), a natural product from rice bran oil-derived gamma-oryzanol, on allergic reaction. When CAF and gamma-oryzanol were injected intradermally with anti-DNP IgE into the dorsal skin of rats, the passive cutaneous anaphylaxis reaction induced by DNP-HSA was attenuated. CAF and gamma-oryzanol also inhibited the degranulation of DNP-IgE sensitized RBL-2H3 mast cells stimulated with anti-DNP-HSA. IgE conjugated with CAF could not be detected by anti-IgE antibody in the ELISA analysis. Although incubation of IgE with CAF did not decrease the amount of IgE, it was possible to precipitate IgE by centrifugation. These results demonstrate that CAF captures IgE, prevents it from binding to FcepsilonRI, and attenuates mast cell degranulation. Copyright 2009 Elsevier GmbH. All rights reserved.

Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.

PubMed

Polotow, Tatiana G; Poppe, Sandra C; Vardaris, Cristina V; Ganini, Douglas; Guariroba, Maísa; Mattei, Rita; Hatanaka, Elaine; Martins, Maria F; Bondan, Eduardo F; Barros, Marcelo P

2015-09-28

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice

PubMed Central

Fritz, Michael; Klawonn, Anna M.; Nilsson, Anna; Singh, Anand Kumar; Zajdel, Joanna; Björk Wilhelms, Daniel; Lazarus, Michael; Löfberg, Andreas; Jaarola, Maarit; Örtegren Kugelberg, Unn; Billiar, Timothy R.; Hackam, David J.; Sodhi, Chhinder P.; Breyer, Matthew D.; Jakobsson, Johan; Schwaninger, Markus; Schütz, Günther; Rodriguez Parkitna, Jan; Saper, Clifford B.; Blomqvist, Anders; Engblom, David

2015-01-01

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type–specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E2 (PGE2) synthesis. Further, we showed that inflammation-induced PGE2 targeted EP1 receptors on striatal dopamine D1 receptor–expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE2-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation. PMID:26690700

Omega-3 polyunsaturated fatty acids alleviate hepatic steatosis-induced inflammation through Sirt1-mediated nuclear translocation of NF-κB p65 subunit in hepatocytes of large yellow croaker (Larmichthys crocea).

PubMed

Wang, Tianjiao; Yang, Bo; Ji, Renlei; Xu, Wei; Mai, Kangsen; Ai, Qinghui

2017-12-01

Hepatic steatosis induced inflammation is becoming increasingly prevalent in farmed fish. This study was conducted to investigate the protective effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) against hepatic steatosis-induced inflammation and its potential molecular mechanisms in hepatocyte of large yellow croaker (Larmichthys crocea). We found that the hepatic steatosis-induced inflammation was relieved by ω-3 PUFAs, meanwhile, the Sirt1 activity and transcript expression was increased by ω-3 PUFAs. The increased Sirt1 activity can decrease the hepatic steatosis-induced inflammation. The protective effects of ω-3 PUFAs against hepatic steatosis-induced inflammation was reversed by the treatment with Sirt1 inhibitor EX-527. The nuclear translocation of nuclear transcription factor kappa-B (NF-κB) p65 was significantly decreased after ω-3 PUFAs treatments compared to the palmitic acid stimulation group. The ω-3 PUFAs induced cytoplasm translocation of NF-κB p65 was reversed by EX-527. Together, ω-3 PUFAs alleviate hepatic steatosis-induced inflammation through Sirt1-mediated nuclear translocation of NF-κB p65 subunit in hepatocytes of large yellow croaker. The present study provides important insight into the mechanisms of the protective effects of ω-3 PUFAs, providing theory bases for alleviating the hepatic steatosis induced inflammation of farmed fish, thereby offering great benefits to the aquaculture industry and fish consumers. Copyright © 2017. Published by Elsevier Ltd.

Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation.

PubMed

Stankovic, Marija; Pantic, Igor; De Luka, Silvio R; Puskas, Nela; Zaletel, Ivan; Milutinovic-Smiljanic, Sanja; Pantic, Senka; Trbovich, Alexander M

2016-03-01

The aim of the study was to examine alteration and possible application of fractal dimension, angular second moment, and correlation for quantification of structural changes in acutely inflamed tissue. Acute inflammation was induced by injection of turpentine oil into the right and left hind limb muscles of mice, whereas control animals received intramuscular saline injection. After 12 h, animals were anesthetised and treated muscles collected. The tissue was stained by hematoxylin and eosin, digital micrographs produced, enabling determination of fractal dimension of the cells, angular second moment and correlation of studied tissue. Histopathological analysis showed presence of inflammatory infiltrate and tissue damage in inflammatory group, whereas tissue structure in control group was preserved, devoid of inflammatory infiltrate. Fractal dimension of the cells, angular second moment and correlation of treated tissue in inflammatory group decreased in comparison to the control group. In this study, we were first to observe and report that fractal dimension of the cells, angular second moment, and correlation were reduced in acutely inflamed tissue, indicating loss of overall complexity of the cells in the tissue, the tissue uniformity and structure regularity. Fractal dimension, angular second moment and correlation could be useful methods for quantification of structural changes in acute inflammation. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Effects of Repeated Intraperitoneal Injection of Pharmaceutical-grade and Nonpharmaceutical-grade Corn Oil in Female C57BL/6J Mice.

PubMed

Hubbard, Jennifer S; Chen, Patty H; Boyd, Kelli L

2017-11-01

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all substances, including vehicles used to solubilize experimental drugs. To date, no studies have evaluated the direct effect of the pharmaceutical classification of a compound on animal wellbeing. In this study, we evaluated intraperitoneal administration of pharmaceutical-grade corn oil, nonpharmaceutical-grade corn oil, and saline in female C57BL/6J mice. Compounds were administered every 48 h for a total of 4 injections. Mice were evaluated clinically by using body weight, body condition score, visual assessment score, CBC, and serum chemistries. Animals were euthanized at 24 h and 14 d after the final injection. Inflammation of the peritoneal wall and mesenteric fat was assessed microscopically by using a semiquantitative scoring system. Saline-dosed groups had lower pathology scores at both time points. At day 21, pharmaceutical-grade corn oil had a significantly higher pathology score compared with nonpharmaceutical-grade corn oil. No other significant differences between the corn oil groups were observed. The use of nonpharmaceutical grade corn oil did not result in adverse clinical consequences and is presumed safe to use for intraperitoneal injection in mice. Differences in inflammation between the 2 groups suggest that the use of either pharmaceutical-grade or nonpharmaceutical-grade corn oil should be consistent within a study.

Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment

PubMed Central

Hosoki, Koa; Aguilera-Aguirre, Leopoldo; Brasier, Allan R.; Kurosky, Alexander; Boldogh, Istvan

2016-01-01

Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPE-induced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation. PMID:26086549

Facilitation of Allergic Sensitization and Allergic Airway Inflammation by Pollen-Induced Innate Neutrophil Recruitment.

PubMed

Hosoki, Koa; Aguilera-Aguirre, Leopoldo; Brasier, Allan R; Kurosky, Alexander; Boldogh, Istvan; Sur, Sanjiv

2016-01-01

Neutrophil recruitment is a hallmark of rapid innate immune responses. Exposure of airways of naive mice to pollens rapidly induces neutrophil recruitment. The innate mechanisms that regulate pollen-induced neutrophil recruitment and the contribution of this neutrophilic response to subsequent induction of allergic sensitization and inflammation need to be elucidated. Here we show that ragweed pollen extract (RWPE) challenge in naive mice induces C-X-C motif ligand (CXCL) chemokine synthesis, which stimulates chemokine (C-X-C motif) receptor 2 (CXCR2)-dependent recruitment of neutrophils into the airways. Deletion of Toll-like receptor 4 (TLR4) abolishes CXCL chemokine secretion and neutrophil recruitment induced by a single RWPE challenge and inhibits induction of allergic sensitization and airway inflammation after repeated exposures to RWPE. Forced induction of CXCL chemokine secretion and neutrophil recruitment in mice lacking TLR4 also reconstitutes the ability of multiple challenges of RWPE to induce allergic airway inflammation. Blocking RWPE-induced neutrophil recruitment in wild-type mice by administration of a CXCR2 inhibitor inhibits the ability of repeated exposures to RWPE to stimulate allergic sensitization and airway inflammation. Administration of neutrophils derived from naive donor mice into the airways of Tlr4 knockout recipient mice after each repeated RWPE challenge reconstitutes allergic sensitization and inflammation in these mice. Together these observations indicate that pollen-induced recruitment of neutrophils is TLR4 and CXCR2 dependent and that recruitment of neutrophils is a critical rate-limiting event that stimulates induction of allergic sensitization and airway inflammation. Inhibiting pollen-induced recruitment of neutrophils, such as by administration of CXCR2 antagonists, may be a novel strategy to prevent initiation of pollen-induced allergic airway inflammation.

A safflower oil based high-fat/high-sucrose diet modulates the gut microbiota and liver phospholipid profiles associated with early glucose intolerance in the absence of tissue inflammation.

PubMed

Danneskiold-Samsøe, Niels Banhos; Andersen, Daniel; Radulescu, Ilinca Daria; Normann-Hansen, Ann; Brejnrod, Asker; Kragh, Marie; Madsen, Tobias; Nielsen, Christian; Josefsen, Knud; Fretté, Xavier; Fjaere, Even; Madsen, Lise; Hellgren, Lars I; Brix, Susanne; Kristiansen, Karsten

2017-05-01

Omega-6 (n-6) PUFA-rich diets are generally considered obesogenic in rodents. Here, we examined how long-term intake of a high-fat/high-sucrose (HF/HS) diet based on safflower oil affected metabolism, inflammation, and gut microbiota composition. We fed male C57BL/6J mice a HF/HS diet based on safflower oil-rich in n-6 PUFAs-or a low-fat/low-sucrose diet for 40 wk. Compared to the low-fat/low-sucrose diet, intake of the safflower-based HF/HS diet only led to moderate weight gain, while glucose intolerance developed at week 5 prior to signs of inflammation, but concurrent with increased levels of linoleic acid and arachidonic acid in hepatic phospholipids. Intake of the HF/HS diet resulted in early changes in the gut microbiota, including an increased abundance of Blautia, while late changes coincided with altered inflammatory profiles and increased fasting plasma insulin. Analysis of immune cells in visceral fat and liver revealed no differences between diets before week 40, where the number of immune cells decreased in the liver of HF/HS-fed mice. We suggest that a diet-dependent increase in the n-6 to omega-3 (n-3) PUFA ratio in hepatic phospholipids together with gut microbiota changes contributed to early development of glucose intolerance without signs of inflammation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Therapeutic Potential of Traditional Chinese Medicine on Inflammatory Diseases

PubMed Central

Tsai, Wen-Hsin; Yang, Chih-Ching; Li, Ping-Chia; Chen, Wang-Chuan; Chien, Chiang-Ting

2013-01-01

Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to cigarette smoke-induced lung inflammation, hepatotoxicity, or sympathetic activation-induced liver inflammation, lipopolysaccharide-induced renal inflammation, and substance P-mediated neurogenic hyperactive bladder based on clinical findings. In this review, we introduce several evidences for TCM treatment including Monascus adlay (MA) produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus on lung injury, Amla (Emblica officinalis Gaertn. of Euphorbiaceae family) on hepatotoxin-induced liver inflammation, Virgate Wormwood Decoction (Yīn Chén Hāo tāng) and its active component genipin on sympathetic activation–induced liver inflammation, and green tea extract and its active components, catechins, or a modified TCM formula Five Stranguries Powder (Wǔ Lén Sǎn) plus Crataegi Fructus (Shān Zhā) on hyperactive bladder. The pathophysiologic and molecular mechanisms of TCM on ameliorating inflammatory diseases are discussed in the review. PMID:24716170

Astaxanthin and β-carotene in Helicobacter pylori-induced Gastric Inflammation: A Mini-review on Action Mechanisms.

PubMed

Kang, Hyunju; Kim, Hyeyoung

2017-06-01

Helicobacter pylori is a dominant bacterium living in the human gastric tissues. In H. pylori -infected tissues, the infiltrated inflammatory cells produce reactive oxygen species (ROS), leading to gastric inflammation with production of various mediators. According to numerous epidemiological studies, dietary carotenoids may prevent gastric inflammation due to their antioxidant properties. Recent studies showed that antioxidant and anti-inflammatory effects of astaxanthin and β-carotene may contribute to inhibition of H. pylori -induced gastric inflammation. Astaxanthin changes H. pylori -induced activation of T helper cell type 1 response towards T helper cell type 2 response in the infected tissues. Astaxanthin inhibits the growth of H. pylori . Even though astaxanthin reduces H. pylori -induced gastric inflammation, it does not reduce cytokine levels in the infected tissues. β-Carotene suppresses ROS-mediated inflammatory signaling, including mitogen-activated protein kinases and redox-sensitive transcription factors, and reduces expression of inflammatory mediators, including interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2 in the infected tissues. Therefore, consumption of astaxanthin- and β-carotene-rich foods may be beneficial to prevent H. pylori -induced gastric inflammation. This review will summarize anti-inflammatory mechanisms of astaxanthin and β-carotene in H. pylori -mediated gastric inflammation.

Regulation of diet-induced adipose tissue and systemic inflammation by salicylates and pioglitazone.

PubMed

Kim, Myung-Sunny; Yamamoto, Yasuhiko; Kim, Kyungjin; Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E; Lee, Jongsoon

2013-01-01

It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6C(hi)), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes.

Investigation into the mechanism of action of essential oil of Pistacia integerrima for its antiasthmatic activity.

PubMed

Shirole, R L; Shirole, N L; Kshatriya, A A; Kulkarni, R; Saraf, M N

2014-05-14

Pistacia integerrima J.L. Stewart ex Brandis locally known as Karkatashringi is an important medicinal plant whose galls are valued in traditional medicine used in India for the treatment of asthma, chronic bronchitis, phthisis, diarrhea, fever, other ailments for the respiratory tract, and as antispasmodic, carminative, antiamoebic and anthelmintic. However, in vitro and in vivo investigations providing new insights into its pharmacological properties have not been thoroughly investigated yet. The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was tested using in vitro studies such as antioxidant activity, mast cell degranulation, angiogenesis, isolated guinea pig ileum preparation and soyabean lipoxidase enzyme activity. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. EOPI (5-30 µg/ml) inhibits 5-lipoxidase enzyme activity with IC50 of 19.71 µg/ml and DPPH scavenging activity up to 100 µg/ml with maximum inhibition of 44.93 ± 2.53% at 100 µg/ml. Pre-treatment with EOPI inhibited erythropoietin-induced angiogenesis. It showed dose dependent (10, 30 and 100 µg/ml) anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation to an extent 19.08 ± 0.47%. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggests that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30mg/kg i.p.) inhibited lipopolysaccharide-induced increase in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Roflumilast was used as a standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

PubMed

Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

2014-04-01

Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

4. GENERAL VIEW SHOWING INDIAN CREEK (FOREGROUND) AND CULVERT. AQUEDUCT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. GENERAL VIEW SHOWING INDIAN CREEK (FOREGROUND) AND CULVERT. AQUEDUCT PASSES ABOVE CULVERT. - Old Croton Aqueduct, Indian Creek Culvert, Reservoir & Quaker Bridge Roads, Crotonville, Ossining, Westchester County, NY

Suppression of lipopolysaccharide-stimulated cytokine/chemokine production in skin cells by sandalwood oils and purified α-santalol and β-santalol.

PubMed

Sharma, M; Levenson, C; Bell, R H; Anderson, S A; Hudson, J B; Collins, C C; Cox, M E

2014-06-01

Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme-linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co-cultured human dermal fibroblasts and neo-epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α-santalol and β-santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α-santalol and β-santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α-santalol and β-santalol also suppressed lipopolysaccharide-induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co-cultures. The ability of SOs to mimic ibuprofen non-steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects. Copyright © 2013 John Wiley & Sons, Ltd.

Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.

PubMed

Kanamori, Hiroyuki; Nakade, Yukiomi; Yamauchi, Taeko; Sakamoto, Kazumasa; Inoue, Tadahisa; Yamamoto, Takaya; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sumida, Yoshio; Nakao, Haruhisa; Fukuzawa, Yoshitaka; Yoneda, Masashi

2017-01-01

Nicotine, a major compound in cigarette smoke, decreases food intake and body weight gain in mammals; however, the influence of nicotine on the progression of non-alcoholic steatohepatitis (NASH) remains controversial. This study aimed to investigate the effect of nicotine on NASH in rat models. Male Wistar rats were fed choline-deficient, l-amino acid-defined (CDAA) diet and treated with nicotine or saline. Food intake, body weight gain, presence of hepatic steatosis, inflammation, and fibrosis were assessed 6 weeks after the rats were fed CDAA diet. Hepatic branch vagotomy was performed to elucidate the mechanism through which nicotine affected steatohepatitis. CDAA diet induced hepatic steatosis, inflammation, and fibrosis, as well as increased the expression of inflammation-related genes. Conversely, nicotine significantly attenuated food intake, body weight gain, and inhibited the CDAA-diet-induced hepatic steatosis, inflammation, and fibrosis, together with increased expression of inflammation-related genes. Hepatic branch vagotomy by itself decreased food intake, body weight gain, and attenuated the CDAA-diet-induced hepatic steatosis, but not inflammation. However, nicotine did not change the food intake, body weight gain, and CDAA diet-induced hepatic steatosis and inflammation in vagotomized rats. These results suggest that nicotine attenuates the CDAA-diet-induced hepatic steatosis and inflammation through the hepatic branch of the vagus nerve in rats.

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

PubMed Central

Yang, Rui; Chen, Wei; Lu, Ye; Li, Yingke; Du, Hongli; Gao, Songyan; Dong, Xin; Yuan, Hongbin

2017-01-01

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation. PMID:28059131

A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.

PubMed

Ren, Xiaomeng; Li, Xinzhi; Jia, Linna; Chen, Deheng; Hou, Hai; Rui, Liangyou; Zhao, Yujun; Chen, Zheng

2017-02-01

Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-κB-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo Furthermore, in vivo administration of B022 protected against not only NIK but also CCl 4 -induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.-Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury. © FASEB.

Dietary and Pharmacological Intervention to Mitigate the ...

EPA Pesticide Factsheets

Background: Human exposure to air pollution has long been associated with excess morbidity and mortality. Although regulatory measures carried out under the “Clean Air Act” have saved millions of lives, there are still hundreds of thousands of people in the U.S. that live in area in which particulate air pollution (PM) levels exceed the U.S. Environmental Protection Agency’s Ambient Air Quality Standard for PM. Therefore, there is an urgent need to identify interventional strategies that can ameliorate the adverse health effects from air pollution exposure. Since the health effects of air pollution exposure are believed to be mediated by inflammation and oxidative stress, one approach is to use dietary supplementation or medication with anti-inflammatory or antioxidant properties. Scope of Review: This article reviews the efficacy of dietary supplementation, such as antioxidant vitamins, polyunsaturated fatty acids, and medications as a strategy to mitigate air pollution-induced adverse cardiopulmonary effects. Major Conclusions: Antioxidant vitamins C and E protect the lungs against ozone and PM exposure. Polyunsaturated fatty acids, such as fish oil and olive oil appears to offer protection against air pollution-induced adverse cardiovascular effects. General Significance: Taking dietary supplements or medications with antioxidant or anti-inflammatory properties has the potential to provide at least partial protection against air pollution in those indiv

Trehalose 6,6′-Dimycolate and Lipid in the Pathogenesis of Caseating Granulomas of Tuberculosis in Mice

PubMed Central

Hunter, Robert L.; Olsen, Margaret; Jagannath, Chinnaswamy; Actor, Jeffrey K.

2006-01-01

Trehalose 6,6′-dimycolate (TDM) is the most abundant, most granulomagenic, and most toxic lipid extractable from the surface of virulent Mycobacterium tuberculosis (MTB). We further examined its toxicity, which requires activation by oily surfaces. Injections of MTB and/or TDM into sensitized mice induced caseating granulomas that centered on oil droplets. If large doses of MTB were injected in saline, caseating granulomas developed in adipose tissue, but MTB with surface TDM removed induced only acute inflammation that did not persist. Variations in protocols produced several variants of caseating granulomas, each with characteristics of human tuberculosis. In each instance, MTB were localized in fat cells or oil drops during initiation of caseating granulomas suggesting that necrosis was caused by activation of the toxicity of TDM toxicity. Evidence extending these findings to the lung was derived from the observation that in sensitized mice, as in humans, tuberculosis development stimulates accumulation of lipid selectively in alveoli. MTB preferentially associated with lipid droplets in developing necrotic foci in late-stage murine tuberculosis. This supports the hypothesis that pulmonary tuberculosis sequesters MTB in a protected environment that accumulates lipid until it is able to activate the toxicity of TDM and initiate necrosis that results in caseating granulomas. PMID:16565499

Genotoxic activity and induction of biotransformation enzymes in two human cell lines after treatment by Erika fuel extract.

PubMed

Amat-Bronnert, Agnès; Castegnaro, Marcel; Pfohl-Leszkowicz, Annie

2007-01-01

On 12 December 1999, the tanker Erika broke in two parts at about 60km from the Brittany French coasts (Point of Penmarc'h, Sud Finistère, France). About 10,000tonnes of heavy oil fuel were released in the sea. DNA adduct have been detected in fish liver and mussels digestive gland exposed to the Erika oil spill. In order to investigate the mechanism by which Erika fuel extract exhibits genotoxic effects the induction of DNA adducts by an Erika fuel extract have been analysed on two cell lines, human epithelial bronchial cells (WI) and human hepatoma cells. DNA adducts, reflected by a diagonal radioactive zone and individual adducts are detected only in hepatoma cells indicating biotransformation via CYP 1A2 and CYP 1B1. In addition, Erika fuel extract induces some metabolizing enzymes such CYP 1A2, COX2 and 5-LOX, the two later are involved in cancer processes. Formation of leucotrienes B4 (LTB(4)), a mediator playing a role in inflammation, is induced in epithelial bronchial cells. Since inhalation is one of the ways of contamination for human, the above results are important for human health and prevention. Copyright © 2006 Elsevier B.V. All rights reserved.

Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice.

PubMed

Soni, Nikul K; Ross, Alastair B; Scheers, Nathalie; Savolainen, Otto I; Nookaew, Intawat; Gabrielsson, Britt G; Sandberg, Ann-Sofie

2016-09-03

Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial β-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

PubMed

Lei, Yang; Zhou, Ai-Min; Guo, Tao; Tan, Ye; Tao, Yan-Yan; Liu, Cheng-Hai

2013-04-01

To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, Ram Vinod; Pratheeshkumar, Poyil; Son, Yong-O

Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Cr(VI) has been associated with adenocarcinomas and squamous cell carcinoma of the lung. The present study shows that acute Cr(VI) treatment in human bronchial epithelial cells (BEAS-2B) increased inflammatory responses (TNF-α, COX-2, and NF-кB/p65) and expression of Nrf2. Cr(VI)-induced generation of reactive oxygen species (ROS) are responsible for increased inflammation. Despite the fact that Nrf2 is a master regulator of response to oxidative stress, silencing of Nrf2 in the acute Cr(VI) treatment had no effect on Cr(VI)-induced inflammation. In contrast, in Cr(VI)-transformed (CrT) cells, Nrf2 is constitutively activated. Knock-down of thismore » protein resulted in decreased inflammation, while silencing of SOD2 and CAT had no effect in the expression of these inflammatory proteins. Results obtained from the knock-down of Nrf2 in CrT cells are very different from the results obtained in the acute Cr(VI) treatment. In BEAS-2B cells, knock-down of Nrf2 had no effect in the inflammation levels, while in CrT cells a decrease in the expression of inflammation markers was observed. These results indicate that before transformation, ROS plays a critical role while Nrf2 not in Cr(VI)-induced inflammation, whereas after transformation (CrT cells), Nrf2 is constitutively activated and this protein maintains inflammation while ROS not. Constitutively high levels of Nrf2 in CrT binds to the promoter regions of COX-2 and TNF-α, leading to increased inflammation. Collectively, our results demonstrate that before cell transformation ROS are important in Cr(VI)-induced inflammation and after transformation a constitutively high level of Nrf2 is important. - Highlights: • Cr(VI)-induced ROS increased inflammation, while Nrf2 had no effect. • In the CrT cells knock-down of Nrf2 resulted in decreased inflammation. • Mechanistic differences in regulating Cr(VI)-induced inflammation.« less

Odor Signals of Immune Activation and CNS Inflammation

DTIC Science & Technology

2014-12-01

inflammation results in detectable alteration of body odor and that traumatic brain injury (TBI) might similarly produce volatile metabolites specific to...Because both LPS and TBI elicit inflammatory processes and LPS-induced inflammation induces body odor changes, we hypothesized that (1) TBI would...induce a distinct change in body odor and (2) this change would resemble the change induced by LPS. Mice receiving surgery and lateral fluid percussion

Renewable Enhanced Feedstocks for Advanced Biofuels and Bioproducts (REFABB)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peoples, Oliver; Snell, Kristi

The basic concept of the REFABB project was that by genetically engineering the biomass crop switchgrass to produce a natural polymer PHB, which is readily broken down by heating (thermolysis) into the chemical building block crotonic acid, sufficient additional economic value would be added for the grower and processor to make it an attractive business at small scale. Processes for using thermolysis to upgrade biomass to densified pellets (char) or bio-oil are well known and require low capital investment similar to a corn ethanol facility. Several smaller thermolysis plants would then supply the densified biomass, which is easier to handlemore » and transport to a centralized biorefinery where it would be used as the feedstock. Crotonic acid is not by itself a large volume commodity chemical, however, the project demonstrated that it can be used as a feedstock to produce a number of large volume chemicals including butanol which itself is a biofuel target. In effect the project would try to address three key technology barriers, feedstock logistics, feedstock supply and cost effective biomass conversion. This project adds to our understanding of the potential for future biomass biorefineries in two main areas. The first addressed in Task A was the importance and potential of developing an advanced value added biomass feedstock crop. In this Task several novel genetic engineering technologies were demonstrated for the first time. One important outcome was the identification of three novel genes which when re-introduced into the switchgrass plants had a remarkable impact on increasing the biomass yield based on dramatically increasing photosynthesis. These genes also turned out to be critical to increasing the levels of PHB in switchgrass by enabling the plants to fix carbon fast enough to support both plant growth and higher levels of the polymer. Challenges in the critical objective of Task B, demonstrating conversion of the PHB in biomass to crotonic acid at over 90% yield, demonstrated the need to consider up-front the limitations of trying to adopt existing equipment to a task for which subsequent basic research studies indicated it was not suitable. New information was developed in the most complex of the chemical conversions studied, advanced catalysis to make acrylic acid, a chemical used widely to make paints, and this was published in a scientific journal. In regard to the technical effectiveness, the crop science aspects were for the most part remarkably effective in addressing the underlying objectives indicating the soundness of the technical approach. With time, it should be possible to fully develop the advanced biomass biorefinery feedstock. Challenges within the thermolysis step to recover crotonic acid meant that by the end of the project we were not able to demonstrate an economic case based on data from scaled up equipment. Solving this will take further research and development work. As a general statement, the broadest public good is in demonstrating the value of funding a very unique approach to the complex problem of enabling large-scale biomass biorefineries which resulted in significant progress towards the ultimate goal and a clearer understanding of the technical hurdles remaining. Perhaps not surprisingly, some of the broader benefits to the public come from the use of the REFABB project innovations in areas unrelated to the initial objective. It is worth highlighting the breakthrough developments in identifying three single global regulator genes which can be engineered into plants to dramatically increase photosynthesis and carbon capturing ability. These genes have tremendous potential for use in major food crops, in particular corn to enhance grain yield and based on recent findings, increase the root density, a critical key to increasing carbon sequestration in agriculture and improving the sustainability of global food and biofuel production.« less

Curcumin inhibits adipogenesis induced by benzyl butyl phthalate in 3T3-L1 cells.

PubMed

Sakuma, Satoru; Sumida, Maki; Endoh, Yukiko; Kurita, Ayaka; Yamaguchi, Ayana; Watanabe, Tomoki; Kohda, Tetsuya; Tsukiyama, Yui; Fujimoto, Yohko

2017-08-15

Phthalates are a group of endocrine disrupting chemicals and may have contributed to the recent global obesity health crisis. Increased adipogenesis via the peroxisome proliferator-activated receptor γ (PPARγ)-CCAAT-enhancer binding protein α (C/EBPα) pathway could be one critical mechanism responsible for phthalate-induced weight gain. On the other hand, curcumin has been shown to inhibit adipogenesis in cells and animal models. The present study was undertaken to evaluate, for the first time, whether curcumin could reduce adipogenesis induced by benzyl butyl phthalate (BBP) via downregulation of the PPARγ-C/EBPα pathway. 3T3-L1 preadipocytes were differentiated by treating them with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of BBP, with or without curcumin. Cells that were grown in the presence of BBP alone showed a significant increase in triacylglycerol (TG) levels. In addition, the number of Oil Red O-stained cells and the mRNA expression levels of PPARγ, C/EBPα, adiponectin, and tumor necrosis factor-α (TNFα) were significantly increased. However, treatment with BBP in combination with curcumin resulted in major reductions in TG levels, the numbers of Oil Red O-stained cells, and the mRNA expression levels of the four proteins. These results suggest that curcumin might be an inhibitor of BBP-induced weight gain and inflammation via stimulation of adipocyte differentiation and TNFα generation. Curcumin may, therefore, be a potential medication for preventing the harmful effects of phthalates. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 74510 - National Register of Historic Places; Notification of Pending Nominations and Related Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-14

...., Troy, 12001132 Westchester County Downtown Ossining Historic District (Boundary Increase), Main St., Central & Croton Aves., Ossining, 12001133 TEXAS Walker County Austin Hall, 1741 University Ave...

5. GENERAL VIEW SHOWING CULVERT. BUTTRESSING ON LEFT AND RIGHT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. GENERAL VIEW SHOWING CULVERT. BUTTRESSING ON LEFT AND RIGHT WAS ADDED AT A LATER DATE. - Old Croton Aqueduct, Indian Creek Culvert, Reservoir & Quaker Bridge Roads, Crotonville, Ossining, Westchester County, NY

6. Photocopied December 1977, from loose original engineering drawing, Jervis ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. Photocopied December 1977, from loose original engineering drawing, Jervis Library. IRON PLATES OVER BRIDGE. - Old Croton Aqueduct, Sing Sing Kill Bridge, Spanning Aqueduct Street & Broadway, Ossining, Westchester County, NY

1. Photocopied December, 1977, from loose original engineering drawing, Jervis ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Photocopied December, 1977, from loose original engineering drawing, Jervis Library. SECTIONS OF INDIAN BROOK CLUVERT - Old Croton Aqueduct, Indian Creek Culvert, Reservoir & Quaker Bridge Roads, Crotonville, Ossining, Westchester County, NY

4. Photocopied December 1977, from loose original engineering drawing, Jervis ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Photocopied December 1977, from loose original engineering drawing, Jervis Library. CENTERING FOR 88-FOOT ARCH. - Old Croton Aqueduct, Sing Sing Kill Bridge, Spanning Aqueduct Street & Broadway, Ossining, Westchester County, NY

DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway

USDA-ARS?s Scientific Manuscript database

Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...

Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice.

PubMed

Yamazaki, Tomomi; Nakamori, Akiko; Sasaki, Eriko; Wada, Satoshi; Ezaki, Osamu

2007-12-01

Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). We analyzed the effects of dietary fish oil on fatty liver induced by sucrose, safflower oil, and butter in ddY mice. In experiment I, mice were fed a high-starch diet [70 energy% (en%) starch] plus 20% (wt/wt) sucrose in the drinking water or fed a high-safflower oil diet (60 en%) for 11 weeks. As a control, mice were fed a high-starch diet with drinking water. Fish oil (10 en%) was either supplemented or not. Mice supplemented with sucrose or fed safflower oil showed a 1.7-fold or 2.2-fold increased liver triglyceride content, respectively, compared with that of control mice. Fish oil completely prevented sucrose-induced fatty liver, whereas it exacerbated safflower oil-induced fatty liver. Sucrose increased SREBP-1c and target gene messenger RNAs (mRNAs), and fish oil completely inhibited these increases. In experiment II, mice were fed a high-safflower oil or a high-butter diet, with or without fish oil supplementation. Fish oil exacerbated safflower oil-induced fatty liver but did not affect butter-induced fatty liver. Fish oil increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and target CD36 mRNA in safflower oil-fed mice. These increases were not observed in sucrose-supplemented or butter-fed mice. The effects of dietary fish oil on fatty liver differ according to the cause of fatty liver; fish oil prevents sucrose-induced fatty liver but exacerbates safflower oil-induced fatty liver. The exacerbation of fatty liver may be due, at least in part, to increased expression of liver PPARgamma.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

PubMed

Couturier-Maillard, A; Froux, N; Piotet-Morin, J; Michaudel, C; Brault, L; Le Bérichel, J; Sénéchal, A; Robinet, P; Chenuet, P; Jejou, S; Dumoutier, L; Renauld, J C; Iovanna, J; Huber, S; Quesniaux, Vfj; Sokol, H; Ryffel, B

2018-05-04

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22 -/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

Biodistribution, pharmacokinetics and PET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc in a sarcoma- and inflammation-bearing mouse model.

PubMed

Liu, Ren-Shyan; Chou, Ta-Kai; Chang, Chih-Hsien; Wu, Chun-Yi; Chang, Chi-Wei; Chang, Tsui-Jung; Wang, Shih-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

2009-04-01

2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), [(18)F]fluoroacetate ([(18)F]FAc) and [(18)F]fluoromisonidazole ([(18)F]FMISO) were all considered to be positron emission tomography (PET) probes for tumor diagnosis, though based on different rationale of tissue uptake. This study compared the biodistribution, pharmacokinetics and imaging of these three tracers in a sarcoma- and inflammation-bearing mouse model. C3H mice were inoculated with 2x10(5) KHT sarcoma cells in the right thigh on Day 0. Turpentine oil (0.1 ml) was injected in the left thigh on Day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc were performed on Day 14 after tumor inoculation. The inflammatory lesions were clearly visualized by [(18)F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. The tumor-to-muscle and inflammatory lesion-to-muscle ratios derived from microPET imaging were 6.79 and 1.48 for [(18)F]FMISO, 8.12 and 4.69 for [(18)F]FDG and 3.72 and 3.19 for [(18)F]FAc at 4 h post injection, respectively. Among these, the tumor-to-inflammation ratio was the highest (4.57) for [(18)F]FMISO compared with that of [(18)F]FDG (1.73) and [(18)F]FAc (1.17), whereas [(18)F]FAc has the highest bioavailability (area under concentration of radiotracer vs. time curve, 116.2 hxpercentage of injected dose per gram of tissue). MicroPET images and biodistribution studies showed that the accumulation of [(18)F]FMISO in the tumor is significantly higher than that in inflammatory lesion at 4 h post injection. [(18)F]FDG and [(18)F]FAc delineated both tumor and inflammatory lesions. Our results demonstrated the potential of [(18)F]FMISO/PET in distinguishing tumor from inflammatory lesion.

Effects of Repeated Intraperitoneal Injection of Pharmaceutical-grade and Nonpharmaceutical-grade Corn Oil in Female C57BL/6J Mice

PubMed Central

Hubbard, Jennifer S; Chen, Patty H; Boyd, Kelli L

2017-01-01

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all substances, including vehicles used to solubilize experimental drugs. To date, no studies have evaluated the direct effect of the pharmaceutical classification of a compound on animal wellbeing. In this study, we evaluated intraperitoneal administration of pharmaceutical-grade corn oil, nonpharmaceutical-grade corn oil, and saline in female C57BL/6J mice. Compounds were administered every 48 h for a total of 4 injections. Mice were evaluated clinically by using body weight, body condition score, visual assessment score, CBC, and serum chemistries. Animals were euthanized at 24 h and 14 d after the final injection. Inflammation of the peritoneal wall and mesenteric fat was assessed microscopically by using a semiquantitative scoring system. Saline-dosed groups had lower pathology scores at both time points. At day 21, pharmaceutical-grade corn oil had a significantly higher pathology score compared with nonpharmaceutical-grade corn oil. No other significant differences between the corn oil groups were observed. The use of nonpharmaceutical grade corn oil did not result in adverse clinical consequences and is presumed safe to use for intraperitoneal injection in mice. Differences in inflammation between the 2 groups suggest that the use of either pharmaceutical-grade or nonpharmaceutical-grade corn oil should be consistent within a study. PMID:29256373

Modulation of Signal Proteins: A Plausible Mechanism to Explain How a Potentized Drug Secale Cor 30C Diluted beyond Avogadro's Limit Combats Skin Papilloma in Mice.

PubMed

Khuda-Bukhsh, Anisur Rahman; Bhattacharyya, Soumya Sundar; Paul, Saili; Dutta, Suman; Boujedaini, Naoual; Belon, Philippe

2011-01-01

In homeopathy, ability of ultra-high diluted drugs at or above potency 12C (diluted beyond Avogadro's limit) in ameliorating/curing various diseases is often questioned, particularly because the mechanism of action is not precisely known. We tested the hypothesis if suitable modulations of signal proteins could be one of the possible pathways of action of a highly diluted homeopathic drug, Secale cornutum 30C (diluted 10(60) times; Sec cor 30). It could successfully combat DMBA + croton oil-induced skin papilloma in mice as evidenced by histological, cytogenetical, immunofluorescence, ELISA and immunoblot findings. Critical analysis of several signal proteins like AhR, PCNA, Akt, Bcl-2, Bcl-xL, NF-κB and IL-6 and of pro-apoptotic proteins like cytochrome c, Bax, Bad, Apaf, caspase-3 and -9 revealed that Sec cor 30 suitably modulated their expression levels along with amelioration of skin papilloma. FACS data also suggested an increase of cell population at S and G2 phases and decrease in sub-G1 and G1 phages in carcinogen-treated drug-unfed mice, but these were found to be near normal in the Sec cor 30-fed mice. There was reduction in genotoxic and DNA damages in bone marrow cells of Sec Cor 30-fed mice, as revealed from cytogenetic and Comet assays. Changes in histological features of skin papilloma were noted. Immunofluorescence studies of AhR and PCNA also suggested reduced expression of these proteins in Sec cor 30-fed mice, thereby showing its anti-cancer potentials against skin papilloma. Furthermore, this study also supports the hypothesis that potentized homeopathic drugs act at gene regulatory level.

BIOLOGICAL AND PHYTOCHEMICAL INVESTIGATIONS OF EXTRACTS FROM PTEROCARPUS ERINACEUS POIR (FABACEAE) ROOT BARKS

PubMed Central

Noufou, Ouédraogo; Anne-Emmanuelle, Hay; Claude W, Ouédraogo Jean; Richard, Sawadogo W; André, Tibiri; Marius, Lompo; Jean-baptiste, Nikiema; Jean, Koudou; Marie-Genevieve, Dijoux-Franca; Pierre, Guissou Innocent

2017-01-01

Background: Pterocarpus erinaceus Poir. belonging to Fabacae familly is used as medicinal plant in Burkina Faso’s folk medicine. Roots of P. erinaceus are used to treat ulcer, stomach ache and inflammatory diseases. The objective of the present study was to carry out phytochemical composition of methanol (MeOH) and dichloromethane (DCM) extracts from Pterocarpus erinaceus roots, to isolate pure compounds, and to evaluate their pharmacological activities. Methods: Chromatographic fractionation led to the isolation of active components of the extracts. The structures were established by NMR analysis and comparison with data from literature. The anti-inflammatory activity was evaluated using croton oil-induced edema of mice ear as well as the effect of extracts against lipoxygenase and lipid peroxidation was evaluated. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Cupric-reducing antioxidant capacity (CUPRAC) methods were used to evaluate the antioxidant activity of the extracts. Results: Friedelin (1), 3a-hydroxyfriedelan-2-one (2), a-sophoradiol (3) and stigmasterol (4) were isolated from DCM extract and maltol-6-O-apiofuranoside-glucopyranoside (5) isolated from MeOH. DCM extract and friedelin, 3a-hydroxyfriedelan-2-one, a-sophoradiol showed a significant anti-inflammatory effect against ear edema. Friedelin (1), α-sophoradiol (3) and maltol-6-O-apiofuranoside-glucopyranoside (5) exhibited lipoxygenase inhibition. MeOH extract (100 μg/mL) inhibited lipoxygenase and lipid peroxidation activities at 45.1 ± 3% and 30.7 ± 0.5% respectively. MeOH extract, ethyl acetate fraction and butanol fraction exhibited antioxidant property with both two methods used. Conclusion: The results suggested that the extracts and compounds from roots of Pterocarpus erinaceus possessed local anti-inflammatory effect, antioxidant properties and inhibitor effect against lipoxygenase and lipid peroxidation activities. PMID:28480397

Expression and Sequence Variants of Inflammatory Genes; Effects on Plasma Inflammation Biomarkers Following a 6-Week Supplementation with Fish Oil.

PubMed

Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2016-03-15

(1) BACKGROUND: A growing body of literature suggest that polymorphisms (SNPs) from inflammation-related genes could possibly play a role in cytokine production and then interact with dietary n-3 fatty acids (FAs) to modulate inflammation. The aim of the present study was to test whether gene expression of selected inflammatory genes was altered following an n-3 PUFA supplementation and to test for gene-diet interactions modulating plasma inflammatory biomarker levels. (2) METHODS: 191 subjects completed a 6-week n-3 FA supplementation with 5 g/day of fish oil. Gene expression of TNF-α and IL6 was assessed in peripheral blood mononuclear cells (PBMCs) using the TaqMan technology. Genotyping of 20 SNPs from the TNF-LTA gene cluster, IL1β, IL6 and CRP genes was performed. (3) RESULTS: There was no significant reduction of plasma IL-6, TNF-α and C-reactive protein (CRP) levels after the 6-week fish oil supplementation. TNF-α and IL6 were slightly overexpressed in PBMCs after the supplementation (fold changes of 1.05 ± 0.38 and 1.18 ± 0.49, respectively (n = 191)), but relative quantification (RQ) within the -0.5 to 2.0 fold are considered as nonbiologically significant. In a MIXED model for repeated measures adjusted for the effects of age, sex and BMI, gene by supplementation interaction effects were observed for rs1143627, rs16944, rs1800797, and rs2069840 on IL6 levels, for rs2229094 on TNF-α levels and for rs1800629 on CRP levels (p < 0.05 for all). (4) CONCLUSIONS: This study shows that a 6-week n-3 FA supplementation with 5 g/day of fish oil did not alter gene expression levels of TNF-α and IL6 in PBMCs and did not have an impact on inflammatory biomarker levels. However, gene-diet interactions were observed between SNPs within inflammation-related genes modulating plasma inflammatory biomarker levels.

Opportunities for probiotics and polyunsaturated fatty acids to improve metabolic health of overweight pregnant women.

PubMed

Mokkala, K; Röytiö, H; Ekblad, U; Laitinen, K

2017-02-07

Overweight during pregnancy predisposes both the mother and foetus to health complications. Maternal complications include gestational diabetes, obstetric problems and type 2 diabetes later in life. Complications for the offspring are not only restricted to the foetal period or birth, such as prematurity and foetal macrosomia, but may also have long-term metabolic health implications through the mechanism of early nutrition programming. One of the key metabolic components characterising overweight in the non-pregnant state is low-grade inflammation manifested by elevated levels of circulatory pro-inflammatory cytokines. In pregnancy, in addition to adipose tissue and placenta, inflammatory response may originate from the gut. The extent to which overweight induces metabolic maladaptation during pregnancy and further compromises maternal and child health is currently poorly understood. In this review, we evaluate recent scientific literature and describe the suggested links between overweight, gut and low-grade inflammation associated metabolic disorders. We focus on overweight pregnant women and gestational diabetes, and discuss how specific dietary factors, probiotics and long-chain polyunsaturated fatty acids (fish oil), might confer health benefits in combatting against metabolic risk factors.

Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease

PubMed Central

de Souza, Priscilla Azambuja Lopes; Marcadenti, Aline; Portal, Vera Lúcia

2017-01-01

Coronary artery disease (CAD) is responsible for more than 7 million deaths worldwide. In the early stages of the development of atherosclerotic plaques, cardiovascular risk factors stimulate vascular endothelial cells, initiating an inflammatory process, fundamental in the pathogenesis of CAD. The inclusion of potentially cardioprotective foods, such as olive oil, to the diet, may aid in the control of these risk factors, and in the reduction of cytokines and inflammatory markers. The present review aims to address the interaction between phenolic compounds present in olive oil, and inflammation, in the prevention and treatment of CAD. In vitro and in vivo studies suggest that phenolic compounds, such as hydroxytyrosol, tyrosol, and their secoiridoid derivatives, may reduce the expression of adhesion molecules and consequent migration of immune cells, modify the signaling cascade and the transcription network (blocking the signal and expression of the nuclear factor kappa B), inhibit the action of enzymes responsible for the production of eicosanoids, and consequently, decrease circulating levels of inflammatory markers. Daily consumption of olive oil seems to modulate cytokines and inflammatory markers related to CAD in individuals at risk for cardiovascular diseases. However, clinical studies that have evaluated the effects of olive oil and its phenolic compounds on individuals with CAD are still scarce. PMID:28973999

Topical atorvastatin ameliorates 12-O-tetradecanoylphorbol-13-acetate induced skin inflammation by reducing cutaneous cytokine levels and NF-κB activation.

PubMed

Kulkarni, Nagaraj M; Muley, Milind M; Jaji, Mallikarjun S; Vijaykanth, G; Raghul, J; Reddy, Neetin Kumar D; Vishwakarma, Santosh L; Rajesh, Navin B; Mookkan, Jeyamurugan; Krishnan, Uma Maheswari; Narayanan, Shridhar

2015-06-01

Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor used in the treatment of atherosclerosis and dyslipidemia. Studies have evaluated the utility of statins in the treatment of skin inflammation but with varied results. In the present study, we investigated the effect of atorvastatin on TNF-α release and keratinocyte proliferation in vitro and in acute and chronic 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation in vivo. Atorvastatin significantly inhibited lipopolysacharide induced TNF-α release in THP-1 cells and keratinocyte proliferation in HaCaT cells. In an acute study, topical atorvastatin showed dose dependent reduction in TPA induced skin inflammation with highest efficacy observed at 500 µg/ear dose. In chronic study, topical atorvastatin significantly reduced TPA induced ear thickness, ear weight, cutaneous cytokines, MPO activity and improved histopathological features comparable to that of dexamethasone. Atorvastatin also inhibited TPA stimulated NF-κB activation in mouse ear. In conclusion, our results suggest that atorvastatin ameliorates TPA induced skin inflammation in mice at least in part, due to inhibition of cytokine release and NF-κB activation and may be beneficial for the treatment skin inflammation like psoriasis.

Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

PubMed Central

Forney, Laura A.; Lenard, Natalie R.; Stewart, Laura K.

2018-01-01

Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms. PMID:29562620

Remediation System Evaluation, Brewster Wellfield Superfund Site

EPA Pesticide Factsheets

The Brewster Well Field, located on the northern bank of the East Branch Croton River (the “River”),was found in 1978 to be contaminated with chlorinated volatile organic chemicals (CVOCs) includingtetrachloroethene (PCE), trichloroethene (TCE) and..

GENERAL VIEW SHOWING VENTILATOR NUMBER NINE. THIS VENTILATOR IS SLIGHTLY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

GENERAL VIEW SHOWING VENTILATOR NUMBER NINE. THIS VENTILATOR IS SLIGHTLY MORE ORNATE THAN WAS GENERALLY USED BECAUSE OF ITS LOCATION - Old Croton Aqueduct, Ventilator Number 9, Spring & Everett Streets, Ossining, Westchester County, NY

Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.

PubMed

Ghosh, Amiya K; O'Brien, Martin; Mau, Theresa; Yung, Raymond

2017-09-07

Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation.

Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging

PubMed Central

Ghosh, Amiya K.; O'Brien, Martin; Mau, Theresa; Yung, Raymond

2017-01-01

Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation. PMID:28898202

Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis.

PubMed

Murakami, Akira; Furukawa, Ikuyo; Miyamoto, Shingo; Tanaka, Takuji; Ohigashi, Hajime

2013-01-01

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity.

PubMed

McCarty, Mark F; DiNicolantonio, James J

2016-01-01

Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)-about 30%-have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to 'ectopic fat' metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6-C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate.

Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity

PubMed Central

McCarty, Mark F; DiNicolantonio, James J

2016-01-01

Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)—about 30%—have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to ‘ectopic fat’ metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6–C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate. PMID:27547436

Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

PubMed

Ratheesh, M; Sandya, S; Pramod, C; Asha, S; Svenia, Jose P; Premlal, S; GrishKumar, B

2017-02-01

Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and anti-arthritic activity in experimental arthritic model. CB as an anti-arthritic drug has beneficial effect for treating inflammation, tissue damage and pain associated with arthritis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo

Highlights: Black-Right-Pointing-Pointer SIRT1 inactivation decreases autophagy in THP-1 cell. Black-Right-Pointing-Pointer Inhibition of autophagy induces inflammation. Black-Right-Pointing-Pointer SIRT1 inactivation induces inflammation through NF-{kappa}B activation. Black-Right-Pointing-Pointer The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-{kappa}B activation. Black-Right-Pointing-Pointer SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD{sup +}-dependent histone deacetylase, whichmore » is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 through nuclear factor (NF)-{kappa}B signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-{kappa}B activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-{kappa}B activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and is implicated in decreased 5 Prime -AMP activated kinase (AMPK) activation, leading to the impairment of autophagy. The mTOR inhibitor, rapamycin, abolishes Sirtinol-induced inflammation and NF-{kappa}B activation associated with p62/Sqstm1 accumulation. In summary, SIRT1 inactivation induces inflammation through NF-{kappa}B activation and dysregulates autophagy via nutrient-sensing pathways such as the mTOR and AMPK pathways, in THP-1 cells.« less

α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2.

PubMed

Li, Xiao-Jun; Yang, Yan-Jing; Li, Yu-Sang; Zhang, Wei Kevin; Tang, He-Bin

2016-02-17

Frankincense oil and water extracts (FOE, FWE) have long been used for external treatment of inflammation and pain. The present study was conducted to identify the active ingredients responsible for the anti-inflammatory and analgesic effects and to determine the underlying mechanisms. The compositions of FOE and FWE were identified and compared by GC-MS. The anti-inflammatory and analgesic activities of the two extracts and their possible active ingredients (α-pinene, linalool, and 1-octanol) were evaluated and compared in a xylene-induced ear edema model and a formalin-inflamed hind paw model. Inflammatory infiltrates and cyclooxygenase-2 (COX-2) expression in hind paw skin were investigated by histological staining. The contents of α-pinene, linalool, and 1-octanol in FOE were much higher than those in FWE. Mice treated with FOE exhibited greater and faster lessening of swelling and pain than mice treated with FWE. The combination of the three components had more potent pharmacological effects on hind paw inflammation and COX-2 overexpression than the three components used alone. These findings suggest that topical application of FOE or its active ingredients (including α-pinene, linalool, and 1-octanol) exhibit significantly anti-inflammatory and analgesic effects through inhibiting nociceptive stimulus-induced inflammatory infiltrates and COX-2 overexpression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells.

PubMed

Fischer, Horst; Machen, Terry E; Widdicombe, Jonathan H; Carlson, Thomas J S; King, Steven R; Chow, John W S; Illek, Beate

2004-08-01

An oligomeric proanthocyanidin (SP-303) extracted from the bark latex of the tree Croton lechleri (family Euphorbiaceae) is a potent inhibitor of cholera toxin-induced fluid accumulation and chloride secretion. The manufacturing process for SP-303 was optimized and simplified to produce an increased yield of the herbal extract. The novel extract (named SB-300) contained on average 70.6+/-7.2% SP-303 by weight (mean +/- S.D.; n=56 lots). Here, we describe the effectiveness of SB-300 on cAMP-regulated chloride secretion, which is mediated by the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) in human colonic T84 cells. Exposure of the apical surface to SB-300 blocked forskolin-stimulated Cl- secretion by 92.2+/-3.0% with a half-maximal inhibition constant (KB) of 4.8+/-0.8 microM. For SP-303, stimulated Cl- currents were decreased by 98.0+/-7.2 % and KB averaged 4.1+/-1.3 microM. There was no significant difference between the blocking kinetics of SP-303 and SB-300. Forskolin-stimulated whole cell Cl- currents were effectively blocked by extracellular addition of SB-300 (63+/-8.5%; n=3) and to a similar extent by SP-303 (83 +/- 0.6%; n=2; at 50 microM each). Both extracts inhibited a time- and voltage-independent Cl- conductance, which indicated the involvement of CFTR Cl- channels. We conclude that both SP-303 (used in Provir) and SB-300 (used in NSF Normal Stool Formula) are novel natural products that target the CFTR Cl- channel. SB-300 is a low cost herbal extract and may present a complementary and alternative medicine approach for the treatment of fluid loss in watery diarrhea.

Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation.

PubMed

d'Avila, Joana Costa; Siqueira, Luciana Domett; Mazeraud, Aurélien; Azevedo, Estefania Pereira; Foguel, Debora; Castro-Faria-Neto, Hugo Caire; Sharshar, Tarek; Chrétien, Fabrice; Bozza, Fernando Augusto

2018-01-30

Microglia function is essential to maintain the brain homeostasis. Evidence shows that aged microglia are primed and show exaggerated response to acute inflammatory challenge. Systemic inflammation signals to the brain inducing changes that impact cognitive function. However, the mechanisms involved in age-related cognitive decline associated to episodic systemic inflammation are not completely understood. The aim of this study was to identify neuropathological features associated to age-related cognitive decline in a mouse model of episodic systemic inflammation. Young and aged Swiss mice were injected with low doses of LPS once a week for 6 weeks to induce episodic systemic inflammation. Sickness behavior, inflammatory markers, and neuroinflammation were assessed in different phases of systemic inflammation in young and aged mice. Behavior was evaluated long term after episodic systemic inflammation by open field, forced swimming, object recognition, and water maze tests. Episodic systemic inflammation induced systemic inflammation and sickness behavior mainly in aged mice. Systemic inflammation induced depressive-like behavior in both young and aged mice. Memory and learning were significantly affected in aged mice that presented lower exploratory activity and deficits in episodic and spatial memories, compared to aged controls and to young after episodic systemic inflammation. Systemic inflammation induced acute microglia activation in young mice that returned to base levels long term after episodic systemic inflammation. Aged mice presented dystrophic microglia in the hippocampus and entorhinal cortex at basal level and did not change morphology in the acute response to SI. Regardless of their dystrophic microglia, aged mice produced higher levels of pro-inflammatory (IL-1β and IL-6) as well as pro-resolution (IL-10 and IL-4) cytokines in the brain. Also, higher levels of Nox2 expression, oxidized proteins and lower antioxidant defenses were found in the aged brains compared to the young after episodic systemic inflammation. Our data show that aged mice have increased susceptibility to episodic systemic inflammation. Aged mice that showed cognitive impairments also presented higher oxidative stress and abnormal production of cytokines in their brains. These results indicate that a neuroinflammation and oxidative stress are pathophysiological mechanisms of age-related cognitive impairments.

Cellular and Molecular Players in Adipose Tissue Inflammation in the Development of Obesity-induced Insulin Resistance

PubMed Central

Lee, Byung-Cheol; Lee, Jongsoon

2013-01-01

There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. PMID:23707515

Adverse Phototoxic Effect of Essential Plant Oils on NIH 3T3 Cell Line after UV Light Exposure.

PubMed

Binder, Svatopluk; Hanáková, Adéla; Tománková, Kateřina; Pížová, Klára; Bajgar, Robert; Manišová, Barbora; Kejlová, Kristina; Bendová, Hana; Jírová, Dagmar; Kolářová, Hana

2016-09-01

Natural or artificial substances have become an inseparable part of our lives. It is questionable whether adequate testing has been performed in order to ensure these substances do not pose a serious health risk. The principal aim of our research was to clarify the potential risk of adding essential oils to food, beverages and cosmetic products. The toxicity of substances frequently employed in cosmetics, aromatherapy and food industry (bergamot oil, Litsea cubeba oil, orange oil, citral) were investigated using cell line NIH3T3 (mouse fibroblasts) with/without UV irradiation. The MTT assay was used to estimate the cell viability. Reactive oxygen species (ROS) which are products of a number of natural cellular processes such as oxygen metabolism and inflammation were measured to determine the extent of cellular stress. DNA damage caused by strand breaks was examined by comet assay. MTT test determined EC50 values for all tested substances, varying from 0.0023% v/v for bergamot oil to 0.018% v/v for citral. ROS production measurement showed that UV radiation induces oxidative stress to the cell resulting in higher ROS production compared to the control and non-irradiated samples. Comet assay revealed that both groups (UV, without UV) exert irreversible DNA damage resulting in a cell death. Our findings suggest that even low concentrations (lower than 0.0464% v/v) of orange oil can be considered as phototoxic (PIF value 8.2) and probably phototoxic for bergamot oil (PIF value 4.6). We also found significant changes in the cell viability, the ROS production and the DNA after the cells were exposed to the tested chemicals. Even though these substances are widely used as antioxidants it should be noted that they present a risk factor and their use in cosmetic and food products should be minimized. Copyright© by the National Institute of Public Health, Prague 2016

Possible Involvement of Liver Resident Macrophages (Kupffer Cells) in the Pathogenesis of Both Intrahepatic and Extrahepatic Inflammation

PubMed Central

Kakinuma, Yuki; Kimura, Takuya

2017-01-01

Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation. PMID:28804705

Possible Involvement of Liver Resident Macrophages (Kupffer Cells) in the Pathogenesis of Both Intrahepatic and Extrahepatic Inflammation.

PubMed

Kakinuma, Yuki; Kimura, Takuya; Watanabe, Yoshifumi

2017-01-01

Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation.

Longitudinal Strain in the Forearc of a Rollback-Subduction System Forced to Change Length: Structural evolution of the Crotone Basin in NE Calabria, Southern Italy

NASA Astrophysics Data System (ADS)

Reitz, M. A.; Seeber, L.

2009-12-01

Calabria is a continental fragment incorporated into a forearc overriding the WNW directed subduction system. This system rolled back toward ESE across the central Mediterranean during the Neogene to form the Tyrrhenian Basin. Riding above the megathrust, forearcs seek a dynamic equilibrium between boundary stresses (drag below and lateral containments) with body stress (gravity acting on the shape of the forearc). Changes in boundary conditions are balanced by changes in the shape. The internal deformation history of the forearc, therefore, is expected to reflect changes in subduction tectonics during the evolution of the arc. We analyzed the structure of the Crotone Basin, located in northeastern Calabria, which is located in the exposed part of the forearc closest to the deformation front and to the Apennines. The main purpose was to compare the successive phases of deformation in the basin to the known evolution of the arc. We found four distinct events from the late Tortonian to the present. A widespread unconformity correlated with the onset of rollback marks a regional foundering with multidirectional normal growth faults. Following this pervasive and deeply rooted extension, the Crotone Basin experiences a period of parallel and distal sedimentation (Ponda clay). These sediments mark a relative long period (~5ma) of remarkable tectonic quiescence, even though subduction-rollback is moving the arc rapidly (3-5cm/yr) to the ESE. In addition, the forearc is shortening by progressive collision with Apulia (the Apennines) and Africa (the Maghrebides) during this time, but our study area is still far from the oblique collisions occurring at the ends of the forearc. The Messinian Salinity Crisis (5.3-6Ma) causes major instabilities in the accretion by loading it with evaporite deposits first and then removing the water load. Landward (westward) thrusting of the accretionary complex correlates with the Messinian in the Crotone basin and elsewhere along eastern Calabria. A characteristic fluvial conglomerate that locally caps the evaporite sequence records this thrusting by a systematic fracturing of the cobbles. After a well-known mid-Pliocene basin-forming extensional event, we find evidence of a basin-wide contractional event affecting the entire Neogene sequence up to the mid-to-late Pliocene. The data show a north-south compression with vergence to the north. This arc-longitudinal shortening may correlate with mid-Pliocene N-S shortening reported in the southern Apennines. Finally, many of these shortening structures are cut or reactivated by a recent (mid-Pleistocene?) faults, that accommodate extension also directed N-S to NW-SE. Our data show a shift from radial to longitudinal tectonics in the Pliocene as the Crotone basin nears the oblique collision with Apulia. Longitudinal forearc shortening may lead to extension in the Pleistocene, as the forearc squeezes through the narrow between Africa (Sicily) and Apulia, and begins lengthening as rollback consumes progressively wider Ionian lithosphere.

Adipose tissue macrophages in the Development of Obesity-induced Inflammation, Insulin Resistance and Type 2 Diabetes

PubMed Central

Lee, Jongsoon

2014-01-01

It has been increasingly accepted that chronic subacute inflammation plays an important role in the development of insulin resistance and Type 2 Diabetes in animals and humans. Particularly supporting this is that suppression of systemic inflammation in Type 2 Diabetes improves glycemic control; this also points to a new potential therapeutic target for the treatment of Type 2 Diabetes. Recent studies strongly suggest that obesity-induced inflammation is mainly mediated by tissue resident immune cells, with particular attention being focused on adipose tissue macrophages (ATMs). This review delineates the current progress made in understanding obesity-induced inflammation and the roles ATMs play in this process. PMID:23397293

Reversing Breast Cancer-Induced Immune Suppression

DTIC Science & Technology

2014-01-01

same oxidative radicals that MDSC use to facilitate immune suppression. Nrf2 protects cells against inflammation and is stabilized in response to... inflammation , hypoxia, and other factors that are known inducers of MDSC. Since Nrf2 regulates antioxidant response and apoptosis, I hypothesize that... inflammation -induced and conventional MDSC transport of cystine. SASP has no effect on tumor growth, metastatic disease, MDSC accumulation, or MDSC suppressive

Peripheral inflammation is associated with remote global gene expression changes in the brain

PubMed Central

2014-01-01

Background Although the central nervous system (CNS) was once considered an immunologically privileged site, in recent years it has become increasingly evident that cross talk between the immune system and the CNS does occur. As a result, patients with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease or psoriasis, are often further burdened with neuropsychiatric symptoms, such as depression, anxiety and fatigue. Despite the recent advances in our understanding of neuroimmune communication pathways, the precise effect of peripheral immune activation on neural circuitry remains unclear. Utilizing transcriptomics in a well-characterized murine model of systemic inflammation, we have started to investigate the molecular mechanisms by which inflammation originating in the periphery can induce transcriptional modulation in the brain. Methods Several different systemic and tissue-specific models of peripheral toll-like-receptor-(TLR)-driven (lipopolysaccharide (LPS), lipoteichoic acid and Imiquimod) and sterile (tumour necrosis factor (TNF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)) inflammation were induced in C57BL/6 mice. Whole brain transcriptional profiles were assessed and compared 48 hours after intraperitoneal injection of lipopolysaccharide or vehicle, using Affymetrix GeneChip microarrays. Target gene induction, identified by microarray analysis, was validated independently using qPCR. Expression of the same panel of target genes was then investigated in a number of sterile and other TLR-dependent models of peripheral inflammation. Results Microarray analysis of whole brains collected 48 hr after LPS challenge revealed increased transcription of a range of interferon-stimulated genes (ISGs) in the brain. In addition to acute LPS challenge, ISGs were induced in the brain following both chronic LPS-induced systemic inflammation and Imiquimod-induced skin inflammation. Unique to the brain, this transcriptional response is indicative of peripherally triggered, interferon-mediated CNS inflammation. Similar models of sterile inflammation and lipoteichoic-acid-induced systemic inflammation did not share the capacity to trigger ISG induction in the brain. Conclusions These data highlight ISG induction in the brain as being a consequence of a TLR-induced type I interferon response. As considerable evidence links type I interferons to psychiatric disorders, we hypothesize that interferon production in the brain could represent an important mechanism, linking peripheral TLR-induced inflammation with behavioural changes. PMID:24708794

TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation

PubMed Central

Tauseef, Mohammad; Knezevic, Nebojsa; Chava, Koteswara R.; Smith, Monica; Sukriti, Sukriti; Gianaris, Nicholas; Obukhov, Alexander G.; Vogel, Stephen M.; Schraufnagel, Dean E.; Dietrich, Alexander; Birnbaumer, Lutz; Malik, Asrar B.

2012-01-01

Lung vascular endothelial barrier disruption and the accompanying inflammation are primary pathogenic features of acute lung injury (ALI); however, the basis for the development of both remains unclear. Studies have shown that activation of transient receptor potential canonical (TRPC) channels induces Ca2+ entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca2+ signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca2+ entry in ECs in a TLR4-dependent manner. Moreover, deletion of TRPC6 renders mice resistant to endotoxin-induced barrier dysfunction and inflammation, and protects against sepsis-induced lethality. TRPC6 induces Ca2+ entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca2+ entry mediated by TRPC6, in turn, activates the nonmuscle myosin light chain kinase (MYLK), which not only increases lung vascular permeability but also serves as a scaffold to promote the interaction of myeloid differentiation factor 88 and IL-1R–associated kinase 4, which are required for NF-κB activation and lung inflammation. Our findings suggest that TRPC6-dependent Ca2+ entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin. PMID:23045603

Green tea polyphenols avert chronic inflammation-induced myocardial fibrosis of female rats

USDA-ARS?s Scientific Manuscript database

Objective: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. Treatments: Fo...

Reversing Breast Cancer-Induced Immune Suppression

DTIC Science & Technology

2013-01-01

MDSC use to facilitate immune suppression. Nrf2 protects cells against inflammation and is stabilized in response to inflammation , hypoxia, and... inflammation -induced and conventional MDSC transport of cystine. SASP has no effect on tumor growth, metastatic disease, MDSC accumulation, or MDSC...anti-tumor immunity. It has been demonstrated that inflammation enhances xC- expression on MDSC, but higher xC- expression does not enhance the

A mixture of St. John's wort and sea buckthorn oils regresses endometriotic implants and affects the levels of inflammatory mediators in peritoneal fluid of the rat: A surgically induced endometriosis model.

PubMed

İlhan, Mert; Süntar, İpek; Demirel, Mürşide Ayşe; Yeşilada, Erdem; Keleş, Hikmet; Küpeli Akkol, Esra

2016-12-01

Sea buckthorn (Hippophae rhamnoides L.) and St. John's wort (Hypericum perforatum L.) are used as an emmenagog and for the treatment of other gynecological disorders including uterus inflammation and endometriosis. The aim of the present study is to investigate the potential of a mixture of sea buckthorn and St. John's wort oils (HrHp oil) in the treatment of endometriosis. The activity was assessed in surgically induced endometriosis in rats. A 15-mm piece of endometrium was sutured into the abdominal wall. Twenty-eight days later, a second laparotomy was performed to calculate the endometrial foci areas and to score intra-abdominal adhesions. The rats were treated with either vehicle, HrHp oil formulation, or the reference (buserelin acetate). At the end of the experiment all rats were sacrificed and endometriotic foci areas and intra-abdominal adhesions were re-evaluated. The tissue sections were analyzed histopathologically. Peritoneal fluids of the experimental animals were collected in order to detect the levels of tumor necrosis factor-α, vascular endothelial growth factor, and interleukin-6, which might be involved in the etiology of endometriosis. In the HrHp oil-treated group, the volumes of endometriotic implants were found to be significantly decreased (from 50.8 mm 3 to 18.6 mm 3 , p<0.001) without any adhesion (0.0±0.0, p<0.001) when compared to the control group (3.1±0.9). The levels of tumor necrosis factor-α decreased from 7.02±1.33 pg/mL to 4.78±1.02 pg/mL (p<0.01); vascular endothelial growth factor from 17.39±8.52 pg/mL to 9.67±5.04 pg/mL (p<0.01); and interleukin-6 from 50.95±22.84 pg/mL to 29.11±7.45 pg/mL (p<0.01), respectively, after HrHp oil treatment. HrHp oil may be a promising alternative for the treatment of endometriosis. Copyright © 2016. Published by Elsevier B.V.

BMP2-Induced Inflammation Can Be Suppressed by the Osteoinductive Growth Factor NELL-1

PubMed Central

Shen, Jia; James, Aaron W.; Zara, Janette N.; Asatrian, Greg; Khadarian, Kevork; Zhang, James B.; Ho, Stephanie; Kim, Hyun Ju

2013-01-01

Bone-morphogenetic protein 2 (BMP2) is currently the only Food and Drug Administration-approved osteoinductive growth factor used in clinical settings for bone regeneration and repair. However, the use of BMP2 is encumbered by numerous clinical complications, including postoperative inflammation and life-threatening cervical swelling. Thus, methods to prevent BMP2-induced inflammation would have far-reaching clinical implications toward improving current BMP2-based methods for bone regeneration. For the first time, we investigate the potential role of the growth factor Nel-like molecule-1 (NELL-1) in inhibiting BMP2-induced inflammation. Adult rats underwent a femoral bone onlay procedure, treated with either BMP2 protein (4 mg/mL), NELL-1 protein (4 mg/mL), or both proteins combined. Animals were evaluated at 3, 7, and 14 days postoperatively by histology, histomorphometry, immunohistochemistry, and real-time PCR for markers of inflammation (TNFα, IL6). The relative levels of TNFα and IL6 in serum were also detected by ELISA. The mechanism for NELL-1's anti-inflammatory effect was further assessed through examining inflammatory markers and generation of reactive oxygen species (ROS) in the mouse embryonic fibroblast NIH3T3 cells. BMP2 significantly induced local inflammation, including an early and pronounced polymorphonuclear cell infiltration accompanied by increased expression of TNFα and IL6. Treatment with NELL-1 alone elicited no significant inflammatory response. However, NELL-1 significantly attenuated BMP2-induced inflammation by all markers and at all timepoints. These local findings were also confirmed using systemic serum inflammatory biomarkers (TNFα, IL6). In each case, NELL-1 fully reversed BMP2-induced systemic inflammation. Lastly, our findings were recapitulated in vitro, where NELL-1 suppressed BMP2 induced expression of inflammatory markers, as well as NF-κB transcriptional activity and generation of ROS. BMP2-induced inflammation is a serious public health concern with potentially life-threatening complications. In the present study, we observed that the growth factor, NELL-1, significantly attenuates or completely reverses BMP2-induced inflammation. The mechanisms of NELL-1's anti-inflammatory effect are only partially elucidated, and may include reduction of NF-κB transcriptional activity or ROS generation. PMID:23758588

1. GENERAL VIEW SHOWING VENTILATOR NO. 9. THIS VENTILATOR IS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. GENERAL VIEW SHOWING VENTILATOR NO. 9. THIS VENTILATOR IS SLIGHTLY MORE ORNATE THAN WAS GENERALLY USED BECAUSE OF ITS LOCATION. - Old Croton Aqueduct, Ventilator Number 9, Spring & Everett Streets, Ossining, Westchester County, NY

Inhibitory Effects of Vinpocetine on the Progression of Atherosclerosis Are Mediated by Akt/NF-κB Dependent Mechanisms in apoE-/- Mice

PubMed Central

Zhuang, Jianhui; Peng, Wenhui; Li, Hailing; Lu, Yuyan; Wang, Ke; Fan, Fan; Li, Shuang; Xu, Yawei

2013-01-01

Background Recent studies have found additional roles for vinpocetine, a potent phosphodiesterase type I inhibitor, in anti-proliferation and anti-inflammation of vascular smooth muscle cells and cancer cells via different mechanisms. In this study, we attempted to investigate whether vinpocetine protected against atherosclerotic development in apoE-/- mice and explore the underlying anti-atherogenic mechanisms in macrophages. Methodology/Principal Findings Vinpocetine markedly decreased atherosclerotic lesion size in apoE-/- mice measured by oil red O. Masson’s trichrome staining and immunohistochemical analyses revealed that vinpocetine significantly increased the thickness of fibrous cap, reduced the size of lipid-rich necrotic core and attenuated inflammation. In vitro experiments exhibited a significant decrease in monocyte adhesion treated with vinpocetine. Further, active TNF-α, IL-6, monocyte chemoattractant protein-1and matrix metalloproteinase-9 expression induced by ox-LDL were attenuated by vinpocetine in a dose-dependent manner. Similarly, ox-LDL-induced reactive oxygen species were significantly repressed by vinpocetine. Both western blot and luciferase activity assay showed that vinpocetine inhibited the enhanced Akt, IKKα/β, IκBα phosphorylation and NF-κB activity induced by ox-LDL, and the inhibition of NF-κB activity was partly caused by Akt dephosphorylation. However, knockdown of PDE1B did not affect Akt, IKKα/β and IκBα phosphorylation. Conclusions These results suggest that vinpocetine exerts anti-atherogenic effects through inhibition of monocyte adhesion, oxidative stress and inflammatory response, which are mediated by Akt/NF-κB dependent pathway but independent of PDE1 blockade in macrophages. PMID:24349299

Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.

PubMed

Zhuang, Jianhui; Peng, Wenhui; Li, Hailing; Lu, Yuyan; Wang, Ke; Fan, Fan; Li, Shuang; Xu, Yawei

2013-01-01

Recent studies have found additional roles for vinpocetine, a potent phosphodiesterase type I inhibitor, in anti-proliferation and anti-inflammation of vascular smooth muscle cells and cancer cells via different mechanisms. In this study, we attempted to investigate whether vinpocetine protected against atherosclerotic development in apoE(-/-) mice and explore the underlying anti-atherogenic mechanisms in macrophages. Vinpocetine markedly decreased atherosclerotic lesion size in apoE(-/-) mice measured by oil red O. Masson's trichrome staining and immunohistochemical analyses revealed that vinpocetine significantly increased the thickness of fibrous cap, reduced the size of lipid-rich necrotic core and attenuated inflammation. In vitro experiments exhibited a significant decrease in monocyte adhesion treated with vinpocetine. Further, active TNF-α, IL-6, monocyte chemoattractant protein-1 and matrix metalloproteinase-9 expression induced by ox-LDL were attenuated by vinpocetine in a dose-dependent manner. Similarly, ox-LDL-induced reactive oxygen species were significantly repressed by vinpocetine. Both western blot and luciferase activity assay showed that vinpocetine inhibited the enhanced Akt, IKKα/β, IκBα phosphorylation and NF-κB activity induced by ox-LDL, and the inhibition of NF-κB activity was partly caused by Akt dephosphorylation. However, knockdown of PDE1B did not affect Akt, IKKα/β and IκBα phosphorylation. These results suggest that vinpocetine exerts anti-atherogenic effects through inhibition of monocyte adhesion, oxidative stress and inflammatory response, which are mediated by Akt/NF-κB dependent pathway but independent of PDE1 blockade in macrophages.

Spectroscopic and microbiological characterization of labdane diterpene 15,16-epoxy-4-hydroxy-labda-13(16),14-dien-3,12-dione isolated from the stems of Croton jacobinensis

NASA Astrophysics Data System (ADS)

Bernardino, A. C. S. S.; Teixeira, A. M. R.; de Menezes, J. E. S. A.; Pinto, C. C. C.; Santos, H. S.; Freire, P. T. C.; Coutinho, H. D. M.; Sena Junior, D. M.; Bandeira, P. N.; Braz-Filho, R.

2017-11-01

In the present study, the natural product named 15,16-epoxy-4-hydroxy-labda-13(16),14-dien-3,12-dione (C20H28O4), a labdane-type diterpene was isolated from the stems of Croton jacobinensis for the first time. This new compound was characterized by infrared and Raman spectroscopy combined with Density Functional Theory calculation. Additionally, the antimicrobial and modulatory antibiotic activities of the compound towards Escherichia coli and Pseudomonas aeruginosa strains were assessed. The labdane diterpene demonstrated a modulatory effect when combined with the antibiotics assayed against both bacteria. A synergistic effect against Escherichia coli can be observed when the compound is associated with gentamicin, reducing the concentration of this antibiotic that is required to inhibit bacterial growth. Other synergistic effects can be observed with gentamicin and cephalothin antibiotics against P. aeruginosa.

Long-term dietary supplementation with saury oil attenuates metabolic abnormalities in mice fed a high-fat diet: combined beneficial effect of omega-3 fatty acids and long-chain monounsaturated fatty acids.

PubMed

Yang, Zhi-Hong; Inoue, Seika; Taniguchi, Yasuko; Miyahara, Hiroko; Iwasaki, Yusuke; Takeo, Jiro; Sakaue, Hiroshi; Nakaya, Yutaka

2015-12-01

Pacific saury is a common dietary component in East Asia. Saury oil contains considerable levels of n-3 unsaturated fatty acids (PUFA) and long-chain monounsaturated fatty acids (LCMUFA) with aliphatic tails longer than 18 carbons. In our previous study, consumption of saury oil for 4 to 6 wk improved insulin sensitivity and the plasma lipid profile in mice. However, the long-term effects of saury oil on metabolic syndrome (MetS) risk factors remain to be demonstrated. In the current study, we examined the long-term effects of saury oil on mice fed a high-fat diet, and compared the effect of n-3 PUFA EPA and LCMUFA on MetS risk factor in diet-induced obese mice. In Experiment 1, male C57BL/6 J mice were fed either a 32% lard diet (control) or a diet containing 22% lard plus 10% saury oil (saury oil group) for 18 weeks. Although no differences were found in body weight and energy expenditure between the control and saury oil groups, the saury oil diet decreased plasma insulin, non-HDL cholesterol, hepatic steatosis, and adipocyte size, and altered levels of mRNA transcribed from genes involved in insulin signaling and inflammation in adipose tissue. Organ and plasma fatty acid profile analysis revealed that consumption of saury oil increased n-3 PUFA and LCMUFA (especially n-11 LCMUFA) levels in multiple organs, and decreased the fatty acid desaturation index (C16:1/C16:0; C18:1/C18:0) in liver and adipose tissue. In Experiment 2, male C57BL/6 J mice were fed a 32% lard diet (control), a diet containing 28% lard plus 4% EPA (EPA group), or a diet containing 20% lard plus 12% LCMUFA concentrate (LCMUFA group) for 8 weeks. EPA or LCMUFA intake increased organ levels of EPA and LCMUFA, respectively. Consumption of EPA reduced plasma lipid levels and hepatic lipid deposition, and decreased the fatty acid desaturation index in liver and adipose tissue. Consumption of LCMUFA decreased plasma non-HDL cholesterol, improved hyperinsulinemia, and decreased the fatty acid desaturation index in adipose tissue. EPA accumulated mainly in liver, and LCMUFA (especially n-11 LCMUFA) accumulated mainly in white adipose tissue, suggesting their possible individual biological effects for improving MetS. Our results suggest that saury oil-mediated improvement of metabolic syndrome in diet-induced obese mice may possibly be due to a combined effect of n-3 PUFA and LCMUFA.

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids.

PubMed

Arpón, Ana; Milagro, Fermín I; Razquin, Cristina; Corella, Dolores; Estruch, Ramón; Fitó, Montserrat; Marti, Amelia; Martínez-González, Miguel A; Ros, Emilio; Salas-Salvadó, Jordi; Riezu-Boj, José-Ignacio; Martínez, J Alfredo

2017-12-23

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346- CPT1B / CHKB-CPT1B and cg17071192- GNAS/GNASAS , being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes.

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids

PubMed Central

Razquin, Cristina; Estruch, Ramón; Fitó, Montserrat; Martínez-González, Miguel A.; Ros, Emilio

2017-01-01

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346–CPT1B/CHKB-CPT1B and cg17071192–GNAS/GNASAS, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes. PMID:29295516

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

PubMed Central

Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

2016-01-01

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study.

PubMed

Lyte, Joshua M; Gabler, Nicholas K; Hollis, James H

2016-11-05

High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults. Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA. Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p < 0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p > 0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals. Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.

Low grade inflammation inhibits VEGF induced HUVECs migration in p53 dependent manner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panta, Sushil; Yamakuchi, Munekazu; Kagoshima University Hospital, Kagoshima

In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Low dose of TNFα induces mild upregulation and moreover nuclearmore » localization of tumor suppressor protein 53 (P53) which causes decrease in inhibitor of DNA binding-1 (Id1) expression and shuttling to the cytoplasm. In absence of Id1, HUVECs fail to upregulate β{sub 3}-integrin and cell migration is decreased. Connecting low dose of TNFα induced p53 to β{sub 3}-integrin through Id1, we present additional link in cross talk between inflammation and angiogenesis. - Highlights: • Low grade inflammation (low dose of TNF alfa) inhibits VEGF induced endothelial cells migration. • The low grade inflammation with VEGF treatment upregulates P53 to a nonlethal level. • P53 activation inhibits Id1 shuttling to the cytoplasm in endothelial cells. • Inhibition of Id1 resulted in downregulation of β{sub 3}-integrin which cause decrease in cell migration. • Inflammation and angiogenesis might cross-talk by P53 – Id1 – β{sub 3}-integrin pathway in endothelial cells.« less

The effects PCSO-524®, a patented marine oil lipid and omega-3 PUFA blend derived from the New Zealand green lipped mussel (Perna canaliculus), on indirect markers of muscle damage and inflammation after muscle damaging exercise in untrained men: a randomized, placebo controlled trial.

PubMed

Mickleborough, Timothy D; Sinex, Jacob A; Platt, David; Chapman, Robert F; Hirt, Molly

2015-01-01

The purpose of the present study was to evaluate the effects of PCSO-524®, a marine oil lipid and n-3 LC PUFA blend, derived from New Zealand green- lipped mussel (Perna canaliculus), on markers of muscle damage and inflammation following muscle damaging exercise in untrained men. Thirty two untrained male subjects were randomly assigned to consume 1200 mg/d of PCSO- 524® (a green-lipped mussel oil blend) or placebo for 26 d prior to muscle damaging exercise (downhill running), and continued for 96 h following the muscle damaging exercise bout. Blood markers of muscle damage (skeletal muscle slow troponin I, sTnI; myoglobin, Mb; creatine kinase, CK), and inflammation (tumor necrosis factor, TNF-α), and functional measures of muscle damage (delayed onset muscle soreness, DOMS; pressure pain threshold, PPT; knee extensor joint range of motion, ROM; isometric torque, MVC) were assessed pre- supplementation (baseline), and multiple time points post-supplementation (before and after muscle damaging exercise). At baseline and 24 h following muscle damaging exercise peripheral fatigue was assessed via changes in potentiated quadriceps twitch force (∆Qtw,pot) from pre- to post-exhaustive cycling ergometer test in response to supra-maximal femoral nerve stimulation. Compared to placebo, supplementation with the green-lipped mussel oil blend significantly attenuated (p < 0.05) sTnI and TNF-α at 2, 24, 48, 72 and 96 h., Mb at 24, 48, 72, 96 h., and CK-MM at all-time points following muscle damaging exercise, significantly reduced (p < 0.05) DOMS at 72 and 96 h post-muscle damaging exercise, and resulted in significantly less strength loss (MVC) and provided a protective effect against joint ROM loss at 96 h post- muscle damaging exercise. At 24 h after muscle damaging exercise perceived pain was significantly greater (p < 0.05) compared to baseline in the placebo group only. Following muscle damaging exercise ∆Qtw,pot was significantly less (p < 0.05) on the green-lipped mussel oil blend compared to placebo. Supplementation with a marine oil lipid and n-3 LC PUFA blend (PCSO-524®), derived from the New Zealand green lipped mussel, may represent a useful therapeutic agent for attenuating muscle damage and inflammation following muscle damaging exercise.

Nanoparticle distribution during systemic inflammation is size-dependent and organ-specific

NASA Astrophysics Data System (ADS)

Chen, K.-H.; Lundy, D. J.; Toh, E. K.-W.; Chen, C.-H.; Shih, C.; Chen, P.; Chang, H.-C.; Lai, J. J.; Stayton, P. S.; Hoffman, A. S.; Hsieh, P. C.-H.

2015-09-01

This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner. Electronic supplementary information (ESI) available: IF images of brain, heart, low magnification images of spleen, mouse heart rate and blood pressure post-LPS. See DOI: 10.1039/c5nr03626g

Anti-inflammatory effect of cinnamaldehyde and linalool from the leaf essential oil of Cinnamomum osmophloeum Kanehira in endotoxin-induced mice.

PubMed

Lee, Shih-Chieh; Wang, Shih-Yun; Li, Chien-Chun; Liu, Cheng-Tzu

2018-01-01

Cinnamomum osmophloeum Kanehira is a Taiwan native plant that belongs to genus Cinnamomum and is also known as pseudocinnamomum or indigenous cinnamon. Its leaf is traditionally used by local people in cooking and as folk therapy. We previously demonstrated the chemical composition and anti-inflammatory effect of leaf essential oil of Cinnamomum osmophloeum Kanehira of linalool chemotype in streptozotocin-induced diabetic rats and on endotoxin-injected mice. The aim of the present study is to evaluate whether cinnamaldehyde and linalool the active anti-inflammatory compounds in leaf essential oil of Cinnamomum osmophloeum Kanehira. Before the injection of endotoxin, C57BL/6 mice of the experimental groups were administered cinnamaldehyde (0.45 or 0.9 mg/kg body weight) or linalool (2.6 or 5.2 mg/kg body weight), mice of the positive control group were administered the leaf essential oil (13 mg/kg body weight), and mice of the negative group were administered vehicle (corn oil, 4 mL/kg body weight) by gavage every other day for two weeks. All mice received endotoxin (i.p. 10 mg/mL/kg body weight) the next day after the final administration and were killed 12 h after the injection. Normal control mice were pretreated with vehicle followed by the injection with saline. None of the treatment found to affect body weight or food or water intake of mice before the injection of endotoxin. Cinnamaldehyde and linalool were found significantly reversed endotoxin-induced body weight loss and lymphoid organ enlargement compared with vehicle (P < 0.05). Both compounds also significantly lowered endotoxin-induced levels of peripheral nitrate/nitrite, interleukin (IL)-1β, IL-18, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and High-mobility group box 1 protein (HMGB-1), and levels of nitrate/nitrite, IL-1β, TNF-α, and IFN-γ in spleen and mesenteric lymph nodes (MLNs) (P < 0.05). Endotoxin-induced expression of toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88), myeloid differentiation protein 2 (MD2), Nod-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and caspase-1 in spleen and mesenteric lymph nodes (MLNs) were inhibited by all tested doses of cinnamaldehyde and linalool (P < 0.05). Subsequently, the activation of nuclear factor (NF)-κB and the activity of caspase-1 in spleen and MLNs were also suppressed by these two compounds (P < 0.05). In addition, cinnamaldehyde and linalool at the dose equivalent to their corresponding content in the tested dose of the leaf essential oil, which was 0.9 mg/kg and 5.2 mg/kg, respectively, showed similar or slightly less inhibitory activity for most of these inflammatory parameters compared with that of the leaf essential oil. Our data confirmed the potential use of leaf essential oil of Cinnamomum osmophloeum Kanehira as an anti-inflammatory natural product and provide evidence for cinnamaldehyde and linalool as two potent agents for prophylactic use in health problems associated with inflammations that being attributed to over-activated TLR4 and/or NLRP3 signaling pathways. Copyright © 2017. Published by Elsevier B.V.

Variations of transcript profiles between sea otters Enhydra lutris from Prince William Sound, Alaska, and clinically normal reference otters

USGS Publications Warehouse

Miles, A. Keith; Bowen, Lizabeth; Ballachey, Brenda E.; Bodkin, James L.; Murray, M.; Estes, J.L.; Keister, Robin A.; Stott, J.L.

2012-01-01

Development of blood leukocyte gene transcript profiles has the potential to expand condition assessments beyond those currently available to evaluate wildlife health, including sea otters Enhydra lutris, both individually and as populations. The 10 genes targeted in our study represent multiple physiological systems that play a role in immuno-modulation, inflammation, cell protection, tumor suppression, cellular stress-response, xenobiotic metabolizing enzymes, and antioxidant enzymes. These genes can be modified by biological, physical, or anthropogenic impacts and consequently provide information on the general type of stressors present in a given environment. We compared gene transcript profiles of sea otters sampled in 2008 among areas within Prince William Sound impacted to varying degrees by the 1989 ‘Exxon Valdez’ oil spill with those of captive and wild reference sea otters. Profiles of sea otters from Prince William Sound showed elevated transcription in genes associated with tumor formation, cell death, organic exposure, inflammation, and viral exposure when compared to the reference sea otter group, indicating possible recent and chronic exposure to organic contaminants. Sea otters from historically designated oiled areas within Prince William Sound 19 yr after the oil spill had higher transcription of genes associated with tumor formation, cell death, heat shock, and inflammation than those from areas designated as less impacted by the spill.

3. AERIAL VIEW OF SAW MILL RIVER CULVERT. NEPPERHAN AVENUE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. AERIAL VIEW OF SAW MILL RIVER CULVERT. NEPPERHAN AVENUE IS AT LEFT, SLIGHTLY FILLED SAW MILL RIVER CULVERT IS ON RIGHT. - Old Croton Aqueduct, Saw Mill River Culvert, Spanning Nepperhan Avenue, Yonkers, Westchester County, NY

The Croton-Yorktown Model of Individualized Earth Science.

ERIC Educational Resources Information Center

Matthias, George F.; Snyder, Edward B.

1980-01-01

The individualized learning model, discussed in this article, uses an efficient feedback mechanism which incorporates an innovative student evaluation program and a unique system of classroom management. The design provides a model for monitoring student progress. (Author/SA)

5. Photocopied December 1977, from loose original engineering drawing, Jervis ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Photocopied December 1977, from loose original engineering drawing, Jervis Library. SECTION OF AQUEDUCT SHOWING CAST-IRON LINING AS USED OVER BRIDGES. - Old Croton Aqueduct, Sing Sing Kill Bridge, Spanning Aqueduct Street & Broadway, Ossining, Westchester County, NY

Vulvodynia

MedlinePlus

... or skin disease. Your provider also may perform cotton swab test. During this test, the provider will ... or oils that may cause inflammation. Wear all cotton underwear and don't use fabric softener on ...

THE EFFECT OF ADRENOCORTICOTROPIC HORMONE ON INFLAMMATION DUE TO TUBERCULIN HYPERSENSITIVITY AND TURPENTINE AND ON CIRCULATING ANTIBODY LEVELS

PubMed Central

Osgood, Charles K.; Favour, Cutting B.

1951-01-01

The treatment with adrenocorticotropic hormone of guinea pigs sensitized with heat-killed tubercle bacilli caused suppression of their skin reactivity to tuberculin. Similar animals treated with saline did not show this change. Normal guinea pigs treated with adrenocorticotropic hormone showed suppression of inflammation, but not necrosis, produced by intracutaneous oil of turpentine. There was slight, but probably not significant, diminution of inflammation during saline administration. Tuberculin complement-fixing antibody titers were not altered by either adrenocorticotropic hormone or saline administration. Adrenocorticotropic hormone produced marked eosinopenia and lymphopenia in guinea pigs. PMID:14888823

Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis.

PubMed

Vieira de Barros, Karina; Gomes de Abreu, Gilclay; Xavier, Roberta Araujo Navarro; Real Martinez, Carlos Augusto; Ribeiro, Marcelo Lima; Gambero, Alessandra; de Oliveira Carvalho, Patrícia; Silveira, Vera Lúcia Flor

2011-02-01

High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. Copyright © 2011 Elsevier Inc. All rights reserved.

Olive oil polyphenols reduce oxysterols -induced redox imbalance and pro-inflammatory response in intestinal cells.

PubMed

Serra, Gessica; Incani, Alessandra; Serreli, Gabriele; Porru, Laura; Melis, M Paola; Tuberoso, Carlo I G; Rossin, Daniela; Biasi, Fiorella; Deiana, Monica

2018-05-16

Dietary habits may strongly influence intestinal homeostasis. Oxysterols, the oxidized products of cholesterol present in cholesterol-containing foodstuffs, have been shown to exert pro-oxidant and pro-inflammatory effects, altering intestinal epithelial layer and thus contributing to the pathogenesis of human inflammatory bowel diseases and colon cancer. Extra virgin olive oil polyphenols possess antioxidant and anti-inflammatory properties, and concentrate in the intestinal lumen, where may help in preventing intestinal diseases. In the present study we evaluated the ability of an extra virgin olive oil phenolic extract to counteract the pro-oxidant and pro-inflammatory action of a representative mixture of dietary oxysterols in the human colon adenocarcinoma cell line (Caco-2) undergoing full differentiation into enterocyte-like cells. Oxysterols treatment significantly altered differentiated Caco-2 cells redox status, leading to oxidant species production and a decrease of GSH levels, after 1 h exposure, followed by an increase of cytokines production, IL-6 and IL-8, after 24 h. Oxysterol cell treatment also induced after 48 h an increase of NO release, due to the induction of iNOS. Pretreatment with the phenolic extract counteracted oxysterols effects, at least in part by modulating one of the main pathways activated in the cellular response to the action of oxysterols, the MAPK-NF-kB pathway. We demonstrated the ability of the phenolic extract to directly modulate p38 and JNK1/2 phosphorylation and activation of NF-kB, following its inhibitor IkB phosphorylation. The phenolic extract also inhibited iNOS induction, keeping NO concentration at the control level. Our results suggest a protective effect at intestinal level of extra virgin olive oil polyphenols, able to prevent or limit redox unbalance and the onset and progression of chronic intestinal inflammation. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Gender differences in the effect of fish oil on appetite, inflammation and nutritional status in haemodialysis patients.

PubMed

Zabel, R; Ash, S; King, N; Naslund, E; Bauer, J

2010-08-01

Haemodialysis patients show signs of chronic inflammation and reduced appetite, which is associated with a worse clinical status and an increased mortality risk. Fish oil has anti-inflammatory properties and may be useful as a therapeutic treatment. There is limited evidence to indicate the feasibility and efficacy of this intervention in dialysis patients. The present study aimed to compare the effect of 12 weeks of supplementation with fish oil on markers of appetite and inflammation in male and female haemodialysis patients. The study was conducted in 28 haemodialysis patients. All patients were prescribed 3 g of fish oil per day for 12 weeks. Changes in appetite, plasma fatty acid profiles and inflammatory markers were measured at baseline and at 12 weeks. The mean (SD) increase in percent plasma eicosapentaenoic acid was statistically significant [1.1 (0.8) to 4.1 (2.2), P < 0.001], which was a strong indicator of good adherence. There were trends towards reductions in peptide YY (-9%; P = 0.078) and an increase in subjective sensations of hunger (+12%; P = 0.406), which reflects an increase in motivation to eat. Males (n = 13) experienced a more marked increase in hunger compared to females (+23% versus -6%), which was associated with maintenance in C-reactive protein and interleukin-6, and a reduction in soluble intercellular adhesion molecule-1. The results obtained demonstrate meaningful trends towards improvements in subjective appetite and certain inflammatory markers (although no change in dietary intake) and this effect was more pronounced in males. However, the levels of some inflammatory markers increased in females and this requires further study. The high level of adherence achieved indicates that an intervention requiring patients to consume four fish oil capsules per day is achievable. This was a short-term study and the effects need to be confirmed in a randomised controlled trial.

Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

PubMed

Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

2013-08-01

To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

TSG-6 secreted by human umbilical cord-MSCs attenuates severe burn-induced excessive inflammation via inhibiting activations of P38 and JNK signaling.

PubMed

Liu, Lingying; Song, Huifeng; Duan, Hongjie; Chai, Jiake; Yang, Jing; Li, Xiao; Yu, Yonghui; Zhang, Xulong; Hu, Xiaohong; Xiao, Mengjing; Feng, Rui; Yin, Huinan; Hu, Quan; Yang, Longlong; Du, Jundong; Li, Tianran

2016-07-22

The hMSCs have become a promising approach for inflammation treatment in acute phase. Our previous study has demonstrated that human umbilical cord-MSCs could alleviate the inflammatory reaction of severely burned wound. In this study, we further investigated the potential role and mechanism of the MSCs on severe burn-induced excessive inflammation. Wistar rats were randomly divided into following groups: Sham, Burn, Burn+MSCs, Burn+MAPKs inhibitors, and Burn, Burn+MSCs, Burn+Vehicle, Burn+siTSG-6, Burn+rhTSG-6 in the both experiments. It was found that MSCs could only down-regulate P38 and JNK signaling, but had no effect on ERK in peritoneal macrophages of severe burn rats. Furthermore, suppression of P38 and JNK activations significantly reduced the excessive inflammation induced by severe burn. TSG-6 was secreted by MSCs using different inflammatory mediators. TSG-6 from MSCs and recombinant human (rh)TSG-6 all significantly reduced activations of P38 and JNK signaling induced by severe burn and then attenuated excessive inflammations. On the contrary, knockdown TSG-6 in the cells significantly increased phosphorylation of P38 and JNK signaling and reduced therapeutic effect of the MSCs on excessive inflammation. Taken together, this study suggested TSG-6 from MSCs attenuated severe burn-induced excessive inflammation via inhibiting activation of P38 and JNK signaling.

Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production.

PubMed

Kearney, C J; Cullen, S P; Tynan, G A; Henry, C M; Clancy, D; Lavelle, E C; Martin, S J

2015-08-01

TNF promotes a regulated form of necrosis, called necroptosis, upon inhibition of caspase activity in cells expressing RIPK3. Because necrosis is generally more pro-inflammatory than apoptosis, it is widely presumed that TNF-induced necroptosis may be detrimental in vivo due to excessive inflammation. However, because TNF is intrinsically highly pro-inflammatory, due to its ability to trigger the production of multiple cytokines and chemokines, rapid cell death via necroptosis may blunt rather than enhance TNF-induced inflammation. Here we show that TNF-induced necroptosis potently suppressed the production of multiple TNF-induced pro-inflammatory factors due to RIPK3-dependent cell death. Similarly, necroptosis also suppressed LPS-induced pro-inflammatory cytokine production. Consistent with these observations, supernatants from TNF-stimulated cells were more pro-inflammatory than those from TNF-induced necroptotic cells in vivo. Thus necroptosis attenuates TNF- and LPS-driven inflammation, which may benefit intracellular pathogens that evoke this mode of cell death by suppressing host immune responses.

Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production

PubMed Central

Kearney, C J; Cullen, S P; Tynan, G A; Henry, C M; Clancy, D; Lavelle, E C; Martin, S J

2015-01-01

TNF promotes a regulated form of necrosis, called necroptosis, upon inhibition of caspase activity in cells expressing RIPK3. Because necrosis is generally more pro-inflammatory than apoptosis, it is widely presumed that TNF-induced necroptosis may be detrimental in vivo due to excessive inflammation. However, because TNF is intrinsically highly pro-inflammatory, due to its ability to trigger the production of multiple cytokines and chemokines, rapid cell death via necroptosis may blunt rather than enhance TNF-induced inflammation. Here we show that TNF-induced necroptosis potently suppressed the production of multiple TNF-induced pro-inflammatory factors due to RIPK3-dependent cell death. Similarly, necroptosis also suppressed LPS-induced pro-inflammatory cytokine production. Consistent with these observations, supernatants from TNF-stimulated cells were more pro-inflammatory than those from TNF-induced necroptotic cells in vivo. Thus necroptosis attenuates TNF- and LPS-driven inflammation, which may benefit intracellular pathogens that evoke this mode of cell death by suppressing host immune responses. PMID:25613374

Antibacterial and antigelatinolytic effects of Satureja hortensis L. essential oil on epithelial cells exposed to Fusobacterium nucleatum.

PubMed

Zeidán-Chuliá, Fares; Keskin, Mutlu; Könönen, Eija; Uitto, Veli-Jukka; Söderling, Eva; Moreira, José Cláudio Fonseca; Gürsoy, Ulvi K

2015-04-01

The present report examined the effects of essential oils (EOs) from Satureja hortensis L. and Salvia fruticosa M. on the viability and outer membrane permeability of the periodontopathogen Fusobacterium nucleatum, a key bacteria in oral biofilms, as well as the inhibition of matrix metalloproteinase (MMP-2 and MMP-9) activities in epithelial cells exposed to such bacteria. Membrane permeability was tested by measuring the N-phenyl-1-naphthylamine uptake and bacterial viability by using the commercially available Live/Dead BacLight kit. In addition, gelatin zymography was performed to analyze the inhibition of F. nucleatum-induced MMP-2 and MMP-9 activities in HaCaT cells. We showed that 5, 10, and 25 μL/mL of Sat. hortensis L. EO decreased the ratio of live/dead bacteria and increased the outer membrane permeability in a range of time from 0 to 5 min. Treatments with 10 and 25 μL/mL of Sal. fruticosa M. also increased the membrane permeability and 5, 10, and 25 μL/mL of both EOs inhibited MMP-2 and MMP-9 activities in keratinocytes induced after exposure of 24 h to F. nucleatum. We conclude that antibacterial and antigelatinolytic activities of Sat. hortensis L. EO have potential for the treatment of periodontal inflammation.

Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke.

PubMed

Whitehouse, Michael Wellesley; Jones, Mark

2009-10-01

To seek a mechanism linking tobacco smoking with the increased incidence and severity of rheumatoid arthritis, deduced from many retrospective surveys, by studying arthritis/fibrosis development in rats. Rats (>300) received low levels of sodium/potassium thiocyanate (10 or 25 mmol/l) in their drinking water to raise their blood thiocyanate levels, mimicking the elevated levels of blood, salivary and urinary thiocyanate found in smokers. Thiocyanate supplements increased the severity of experimental arthritis induced by tailbase injection of (1) Freund's complete adjuvants (mycobacteria plus various adjuvant-active oils), (2) collagen type-II with Freund's incomplete adjuvant (no mycobacteria), (3) the synthetic lipid amine, avridine in an oil and (4) the natural hydrocarbons squalene (C(30)H(50)) and pristane (C(19)H(40)). This pro-arthritic effect was independent of sex, rat strain or changing diet and housing facilities. Thiocyanate supplements also amplified the acute/persisting inflammatory responses to paw injections of pristane, zymosan and microcrystalline hydroxyapatite. Iodide salts also mimicked some of these effects of thiocyanate. Thiocyanate, a detoxication product of HCN present in tobacco smoke, increased (or even induced) inflammatory responses to several agents causing arthritis or fibrotic inflammation in rats. It, therefore, can act as a co-arthritigen, or 'virulence factor' and could be a therapeutic target to reduce arthritis expression and morbidity.

Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino rats.

PubMed

Kaithwas, Gaurav; Majumdar, Dipak K

2010-06-01

The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.

Effects of Citral on Lipopolysaccharide-Induced Inflammation in Human Umbilical Vein Endothelial Cells.

PubMed

Song, Yan; Zhao, Hongfeng; Liu, Jinyang; Fang, Chao; Miao, Renying

2016-04-01

Citral is an active compound of lemongrass oil which has been reported to have anti-inflammatory effects. In this study, we investigated the effects of citral on lipopolysaccharide (LPS)-induced inflammatory response in a rat model of peritonitis and human umbilical vein endothelial cells (HUVECs). LPS was intraperitoneally injected into rats to establish a peritonitis model. The HUVECs were treated with citral for 12 h before exposure to LPS. The levels of TNF-α and IL-8 were measured using ELISA. Western blotting was used to detect the expression of VCAM-1, ICAM-1, NF-κB, and PPAR-γ. The results showed that citral had a protective effect against LPS-induced peritonitis. Citral decreased the levels of WBCs and inflammatory cytokines TNF-α and IL-6. Citral also inhibited LPS-induced myeloperoxidase (MPO) activity in the peritoneal tissue. Treatment of HUVECs with citral significantly inhibited TNF-α and IL-8 expression induced by LPS. LPS-induced VCAM-1 and ICAM-1 expression were also suppressed by citral. Meanwhile, we found that citral inhibited LPS-induced NF-κB activation in HUVECs. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, citral inhibits LPS-induced inflammatory response via activating PPAR-γ which attenuates NF-κB activation and inflammatory mediator production.

Synergistic Effect of Green Tea Polyphenols and Vitamin D on Chronic Inflammation-Induced Bone Loss in Female Rats

USDA-ARS?s Scientific Manuscript database

Our recent study demonstrated a bone-protective role of green tea polyphenols (GTPs), extracted from green tea, in chronic inflammation-induced bone loss of female rats through reduction of inflammation and oxidative stress. This study further examines effects of GTPs in conjunction with vitamin D (...

A lipidomic study on the regulation of inflammation and oxidative stress targeted by marine ω-3 PUFA and polyphenols in high-fat high-sucrose diets.

PubMed

Dasilva, Gabriel; Pazos, Manuel; García-Egido, Eduardo; Gallardo, José M; Ramos-Romero, Sara; Torres, Josep Lluís; Romeu, Marta; Nogués, María-Rosa; Medina, Isabel

2017-05-01

The ability of polyphenols to ameliorate potential oxidative damage of ω-3 PUFAs when they are consumed together and then, to enhance their potentially individual effects on metabolic health is discussed through the modulation of fatty acids profiling and the production of lipid mediators. For that, the effects of the combined consumption of fish oils and grape seed procyanidins on the inflammatory response and redox unbalance triggered by high-fat high-sucrose (HFHS) diets were studied in an animal model of Wistar rats. A standard diet was used as control. Results suggested that fish oils produced a replacement of ω-6 by ω-3 PUFAs in membranes and tissues, and consequently they improved inflammatory and oxidative stress parameters: favored the activity of 12/15-lipoxygenases on ω-3 PUFAs, enhanced glutathione peroxidases activity, modulated proinflammatory lipid mediators synthesis through the cyclooxygenase (COX) pathways and down-regulated the synthesis de novo of ARA leaded by Δ5 desaturase. Although polyphenols exerted an antioxidative and antiinflammatory effect in the standard diet, they were less effective to reduce inflammation in the HFHS dietary model. Contrary to the effect observed in the standard diet, polyphenols up-regulated COX pathways toward ω-6 proinflammatory eicosanoids as PGE 2 and 11-HETE and decreased the detoxification of ω-3 hydroperoxides in the HFHS diet. As a result, additive effects between fish oils and polyphenols were found in the standard diet in terms of reducing inflammation and oxidative stress. However, in the HFHS diets, fish oils seem to be the one responsible for the positive effects found in the combined group. Copyright © 2017 Elsevier Inc. All rights reserved.

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

PubMed Central

Heisler, Jillian M.; O’Connor, Jason C.

2015-01-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

Aldehyde dedydrogenase-2 plays a beneficial role in ameliorating chronic alcohol-induced hepatic steatosis and inflammation through regulation of autophagy.

PubMed

Guo, Rui; Xu, Xihui; Babcock, Sara A; Zhang, Yingmei; Ren, Jun

2015-03-01

Mitochondrial aldehyde dehydrogenase (ALDH2) plays a critical role in the detoxification of the ethanol metabolite acetaldehyde. This study was designed to examine the impact of global ALDH2 overexpression on alcohol-induced hepatic steatosis. Wild type Friend virus B (FVB) and ALDH2 transgenic mice were placed on a 4% alcohol or control diet for 12 weeks. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and cholesterol, hepatic triglyceride, steatosis, fat metabolism-related proteins, pro-inflammatory cytokines, glutathione (GSH), oxidized glutathione (GSSG), autophagy and autophagy signalling were examined. The role of autophagy was evaluated in alcohol dehydrogenase 1 (ADH1)-transfected human hepatocellular liver carcinoma cells (VA-13) treated with or without the autophagy inducer rapamycin and lysosomal inhibitors. Chronic alcohol intake led to elevated AST-, ALT-levels, bilirubin, AST/ALT ratio, cholesterol, hepatic triglycerides and hepatic fat deposition as evidenced by H&E and Oil Red O staining. Hepatic fat deposition was associated with disturbed levels of fat metabolism-related proteins (fatty acid synthase, SCD1), upregulated interleukin-6, TNF-α, cyclooxygenase, oxidative stress, and loss of autophagy, effects which were attenuated or ablated by the ALDH2 transgene. Moreover, ethanol (100 mM) and acetaldehyde (100 and 500 μM) increased levels of IL-6 and IFN-γ, and suppressed autophagy in VA-13 cells, effects which were markedly alleviated by rapamycin. In addition, lysosomal inhibitors mimicked ethanol-induced p62 accumulation with little additive effect with ethanol. Ethanol significantly suppressed LC3 conversion in the presence of lysosomal inhibitors. In summary, our results revealed that ALDH2 plays a beneficial role in ameliorating chronic alcohol intake-induced hepatic steatosis and inflammation through regulation of autophagy. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

MTOR Suppresses Cigarette Smoke-Induced Epithelial Cell Death and Airway Inflammation in Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Yong; Liu, Juan; Zhou, Jie-Sen; Huang, Hua-Qiong; Li, Zhou-Yang; Xu, Xu-Chen; Lai, Tian-Wen; Hu, Yue; Zhou, Hong-Bin; Chen, Hai-Pin; Ying, Song-Min; Li, Wen; Shen, Hua-Hao; Chen, Zhi-Hua

2018-04-15

Airway epithelial cell death and inflammation are pathological features of chronic obstructive pulmonary disease (COPD). Mechanistic target of rapamycin (MTOR) is involved in inflammation and multiple cellular processes, e.g., autophagy and apoptosis, but little is known about its function in COPD pathogenesis. In this article, we illustrate how MTOR regulates cigarette smoke (CS)-induced cell death, airway inflammation, and emphysema. Expression of MTOR was significantly decreased and its suppressive signaling protein, tuberous sclerosis 2 (TSC2), was increased in the airway epithelium of human COPD and in mouse lungs with chronic CS exposure. In human bronchial epithelial cells, CS extract (CSE) activated TSC2, inhibited MTOR, and induced autophagy. The TSC2-MTOR axis orchestrated CSE-induced autophagy, apoptosis, and necroptosis in human bronchial epithelial cells; all of which cooperatively regulated CSE-induced inflammatory cytokines IL-6 and IL-8 through the NF-κB pathway. Mice with a specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly augmented airway inflammation and airspace enlargement in response to CS exposure, accompanied with enhanced levels of autophagy, apoptosis, and necroptosis in the lungs. Taken together, these data demonstrate that MTOR suppresses CS-induced inflammation and emphysema-likely through modulation of autophagy, apoptosis, and necroptosis-and thus suggest that activation of MTOR may represent a novel therapeutic strategy for COPD. Copyright © 2018 by The American Association of Immunologists, Inc.

FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

PubMed

Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

2018-06-01

Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing inflammation and insulin resistance in obesity and diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats

PubMed Central

Hosseini, Sayed Masoud; Taghiabadi, Elahe; Abnous, Khalil; Hariri, Alireza Timcheh; Pourbakhsh, Hamed; Hosseinzadeh, Hossein

2017-01-01

Objective(s): Long term consumption of ethanol may induce damage to many organs. Ethanol induces its noxious effects through reactive oxygen species production, and lipid peroxidation and apoptosis induction in different tissues and cell types. Previous experiments have indicated the antioxidant characteristics of thymoquinone, the active constituent of Nigella sativa fixed oil, against biologically dangerous reactive oxygen species. This experiment was planned to evaluate the protective effect of thymoquinone against subchronic ethanol toxicity in rats. Materials and Methods: Experiments were performed on six groups. Each group consisted of six animals, including control group (saline, gavage), ethanol-receiving group (3 g/kg/day, gavage), thymoquinone (2.5, 5, 10 mg/Kg/day, intraperitoneally (IP)) plus ethanol and thymoquinone (10 mg/Kg/day, IP) groups. Treatments were carried out in four weeks. Results: Thymoquinone reduced the ethanol-induced increase in the lipid peroxidation and severity of histopathological alteration in liver and kidney tissues. In addition it improved the levels of proinflammatory cytokines in liver tissue. Furthermore, thymoquinone corrected the liver enzymes level including alanine transaminase, aspartate transaminase and alkaline phosphatase in serum and glutathione content in liver and kidney tissues. Other experiments such as Western blot analysis and quantitative real-time RT-PCR revealed that thymoquinone suppressed the expression of Bax/Bcl-2 ratio (both protein and mRNA level), and caspases activation pursuant to ethanol toxicity. Conclusion: This study indicates that thymoquinone may have preventive effects against ethanol toxicity in the liver and kidney tissue through reduction in lipid peroxidation and inflammation, and also interrupting apoptosis. PMID:29085585

The effect of stinging nettle (Urtica dioica) seed oil on experimental colitis in rats.

PubMed

Genc, Zeynep; Yarat, Aysen; Tunali-Akbay, Tugba; Sener, Goksel; Cetinel, Sule; Pisiriciler, Rabia; Caliskan-Ak, Esin; Altıntas, Ayhan; Demirci, Betul

2011-12-01

This study investigated the effect of Urtica dioica, known as stinging nettle, seed oil (UDO) treatment on colonic tissue and blood parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic administration with a 8-cm-long cannula with rats under ether anesthesia, assigned to a colitis group and a colitis+UDO group. Rats in the control group were given saline at the same volume by intracolonic administration. UDO (2.5 mL/kg) was given to the colitis+UDO group by oral administration throughout a 3-day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was given to the control and colitis groups at the same volume by oral administration. At the end of the experiment macroscopic lesions were scored, and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor activity, and superoxide dismutase and myeloperoxidase activities. Colonic tissues were also examined by histological and cytological analysis. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that UDO decreased levels of pro-inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. UDO administration ameliorated the TNBS-induced disturbances in colonic tissue except for MDA. In conclusion, UDO, through its anti-inflammatory and antioxidant actions, merits consideration as a potential agent in ameliorating colonic inflammation.

Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance.

PubMed

Lee, Byung-Cheol; Lee, Jongsoon

2014-03-01

There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation.

PubMed

Lee, Da-In; Park, Mi-Kyung; Kang, Shin Ae; Choi, Jun-Ho; Kang, Seok-Jung; Lee, Jeong-Yeol; Yu, Hak Sun

2016-01-01

Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women.

PubMed

Liong, Stella; Lappas, Martha

2016-04-15

Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1α, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1α was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1α and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1β-induced production of IL-6, IL-8, IL-1β and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-α-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-β, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Requirements for flare reactions of joint inflammation induced in mice by cloned MT4+, Lyt-2- T cells.

PubMed

Klasen, I S; Ladestein, R M; van den Berg, W B; Benner, R

1989-03-01

Joint inflammation was induced in C57B1/6 mice by injection of cloned MT4+, Lyt-2- T cells specific for the antigen methylated bovine serum albumin (mBSA), together with mBSA. In this model, after waning of the inflammation, flare reactions can be induced by a rechallenge with the specific antigen. Herein we show that such flare reactions can still be induced several weeks after waning of the joint inflammation, as was demonstrated both in normal C57B1/6 mice and in athymic C57B1 nude mice. The results in the latter group indicate that T cells of the recipient mice are not necessary for the elicitation of flare reactions. On histologic examination, the inflammatory infiltrates in the knee joints of the nude mice appeared to be mainly granulocytic. The cloned T cells persisted and remained functionally reactive in the knee joint for at least 2 weeks in the absence of the antigen, and thus, in the absence of inflammation. In view of the similarities between induced joint inflammation in mice and rheumatoid arthritis in humans, these data may be relevant to our understanding of the processes involved in the latter disease.

Expression and Sequence Variants of Inflammatory Genes; Effects on Plasma Inflammation Biomarkers Following a 6-Week Supplementation with Fish Oil

PubMed Central

Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2016-01-01

(1) Background: A growing body of literature suggest that polymorphisms (SNPs) from inflammation-related genes could possibly play a role in cytokine production and then interact with dietary n-3 fatty acids (FAs) to modulate inflammation. The aim of the present study was to test whether gene expression of selected inflammatory genes was altered following an n-3 PUFA supplementation and to test for gene–diet interactions modulating plasma inflammatory biomarker levels. (2) Methods: 191 subjects completed a 6-week n-3 FA supplementation with 5 g/day of fish oil. Gene expression of TNF-α and IL6 was assessed in peripheral blood mononuclear cells (PBMCs) using the TaqMan technology. Genotyping of 20 SNPs from the TNF-LTA gene cluster, IL1β, IL6 and CRP genes was performed. (3) Results: There was no significant reduction of plasma IL-6, TNF-α and C-reactive protein (CRP) levels after the 6-week fish oil supplementation. TNF-α and IL6 were slightly overexpressed in PBMCs after the supplementation (fold changes of 1.05 ± 0.38 and 1.18 ± 0.49, respectively (n = 191)), but relative quantification (RQ) within the −0.5 to 2.0 fold are considered as nonbiologically significant. In a MIXED model for repeated measures adjusted for the effects of age, sex and BMI, gene by supplementation interaction effects were observed for rs1143627, rs16944, rs1800797, and rs2069840 on IL6 levels, for rs2229094 on TNF-α levels and for rs1800629 on CRP levels (p < 0.05 for all). (4) Conclusions: This study shows that a 6-week n-3 FA supplementation with 5 g/day of fish oil did not alter gene expression levels of TNF-α and IL6 in PBMCs and did not have an impact on inflammatory biomarker levels. However, gene–diet interactions were observed between SNPs within inflammation-related genes modulating plasma inflammatory biomarker levels. PMID:26999109

The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells.

PubMed

Yoon, Seolah; Kim, Jeongjun; Lee, Hyunghee; Lee, Haerim; Lim, Jonghoon; Yang, Heejeong; Shin, Soon Shik; Yoon, Michung

2017-01-04

Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation. The effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay. Administration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells. These results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil

PubMed Central

Morrison, Martine C.; Mulder, Petra; Stavro, P. Mark; Suárez, Manuel; Arola-Arnal, Anna; van Duyvenvoorde, Wim; Kooistra, Teake; Wielinga, Peter Y.; Kleemann, Robert

2015-01-01

Background and Aims As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore, besides potential health effects conferred by the type of fatty acids in a vegetable oil, other minor components (e.g. phytochemicals) may also have health benefits. Here, we investigated the potential long-term health effects of isocaloric substitution of dietary fat (i.e. partial replacement of saturated by unsaturated fats), as well as putative additional effects of phytochemicals present in unrefined (virgin) oil on development of non-alcoholic fatty liver disease (NAFLD) and associated atherosclerosis. For this, we used pumpkin seed oil, because it is high in unsaturated fatty acids and a rich source of phytochemicals. Methods ApoE*3Leiden mice were fed a Western-type diet (CON) containing cocoa butter (15% w/w) and cholesterol (1% w/w) for 20 weeks to induce risk factors and disease endpoints. In separate groups, cocoa butter was replaced by refined (REF) or virgin (VIR) pumpkin seed oil (comparable in fatty acid composition, but different in phytochemical content). Results Both oils improved dyslipidaemia, with decreased (V)LDL-cholesterol and triglyceride levels in comparison with CON, and additional cholesterol-lowering effects of VIR over REF. While REF did not affect plasma inflammatory markers, VIR reduced circulating serum amyloid A and soluble vascular adhesion molecule-1. NAFLD and atherosclerosis development was modestly reduced in REF, and VIR strongly decreased liver steatosis and inflammation as well as atherosclerotic lesion area and severity. Conclusions Overall, we show that an isocaloric switch from a diet rich in saturated fat to a diet rich in unsaturated fat can attenuate NAFLD and atherosclerosis development. Phytochemical-rich virgin pumpkin seed oil exerts additional anti-inflammatory effects resulting in more pronounced health effects. PMID:26405765

Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil.

PubMed

Morrison, Martine C; Mulder, Petra; Stavro, P Mark; Suárez, Manuel; Arola-Arnal, Anna; van Duyvenvoorde, Wim; Kooistra, Teake; Wielinga, Peter Y; Kleemann, Robert

2015-01-01

As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore, besides potential health effects conferred by the type of fatty acids in a vegetable oil, other minor components (e.g. phytochemicals) may also have health benefits. Here, we investigated the potential long-term health effects of isocaloric substitution of dietary fat (i.e. partial replacement of saturated by unsaturated fats), as well as putative additional effects of phytochemicals present in unrefined (virgin) oil on development of non-alcoholic fatty liver disease (NAFLD) and associated atherosclerosis. For this, we used pumpkin seed oil, because it is high in unsaturated fatty acids and a rich source of phytochemicals. ApoE*3Leiden mice were fed a Western-type diet (CON) containing cocoa butter (15% w/w) and cholesterol (1% w/w) for 20 weeks to induce risk factors and disease endpoints. In separate groups, cocoa butter was replaced by refined (REF) or virgin (VIR) pumpkin seed oil (comparable in fatty acid composition, but different in phytochemical content). Both oils improved dyslipidaemia, with decreased (V)LDL-cholesterol and triglyceride levels in comparison with CON, and additional cholesterol-lowering effects of VIR over REF. While REF did not affect plasma inflammatory markers, VIR reduced circulating serum amyloid A and soluble vascular adhesion molecule-1. NAFLD and atherosclerosis development was modestly reduced in REF, and VIR strongly decreased liver steatosis and inflammation as well as atherosclerotic lesion area and severity. Overall, we show that an isocaloric switch from a diet rich in saturated fat to a diet rich in unsaturated fat can attenuate NAFLD and atherosclerosis development. Phytochemical-rich virgin pumpkin seed oil exerts additional anti-inflammatory effects resulting in more pronounced health effects.

Metabolic markers in Ossabaw pigs fed high fat diets enriched in regular or low α-linolenic acid soy oil

PubMed Central

2013-01-01

Background Soy oil is a major vegetable oil consumed in the US. A recently developed soybean variety produces oil with a lower concentration of α-linolenic acid, hence a higher (n-6)/(n-3) ratio, than regular soy oil. The study was conducted to determine the metabolic impact of the low α-linolenic acid containing soy oil. Methods Ossabaw pigs were fed diets supplemented with either 13% regular soybean oil (SBO), or 13% of the low α-linolenic soybean oil (LLO) or a control diet (CON) without extra oil supplementation, for 8 weeks. Results Serum and adipose tissue α-linolenic acid concentration was higher in pigs fed the SBO diet than those on the CON and LLO diets. In the serum, the concentration of saturated fatty acids (SFA) was lower in the LLO group than in CON and SBO groups polyunsaturated fatty acid (PUFA) concentration was higher in the LLO group compared to CON and SBO groups. Glucose, insulin, triglycerides and LDL-cholesterol were higher in pigs fed the SBO diet than those fed the CON and LLO diets. HDL-cholesterol was lower in pigs on the SBO diet than those on the CON and LLO diets. Pigs fed SBO and LLO diets had lower CRP concentration than those on the CON diet. Adipose tissue expression of Interleukin 6 (IL-6) was higher in the SBO and LLO diets than the CON. Expression of ECM genes, COLVIA and fibronectin, was significantly reduced in the SBO diet relative to the CON and LLO diets whereas expression of inflammation-related genes, cluster of differentiation 68 (CD68) and monocyte chemoattractant protein 1 (MCP-1), was not different across treatments. Conclusions Results suggest that lowering the content of α-linolenic acid in the context of a high fat diet could lead to mitigation of development of hyperinsulinemia and dyslipidemia without significant effects on adipose tissue inflammation. PMID:23497195

4. EXTERIOR VIEW LOOKING EAST. WATER IN THE AQUEDUCT CAN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. EXTERIOR VIEW LOOKING EAST. WATER IN THE AQUEDUCT CAN CAN BE DIVERTED AT THE WASTE WEIR TO BE DISCHARGED INTO THE CULVERT IN FOREGROUND. - Old Croton Aqueduct, Northern Waste Weir, Snowden Avenue & Van Wick Street, Ossining, Westchester County, NY

Neutrophils confer T cell resistance to myeloid-derived suppressor cell-mediated suppression to promote chronic inflammation.

PubMed

Ryan, Sean O; Johnson, Jenny L; Cobb, Brian A

2013-05-15

Low-grade chronic inflammation can persist in aging humans unnoticed for years or even decades, inflicting continuous damage that can culminate later in life as organ dysfunction, physical frailty, and some of the most prominent debilitating and deadly age-associated diseases, including rheumatoid arthritis, diabetes, heart disease, and cancer. Despite the near universal acceptance of these associations, the mechanisms underlying unresolved inflammation remain poorly understood. In this study, we describe a novel inducible method to examine systemic chronic inflammation using susceptible animal models. Induced inflammation results in unresolved innate cellular responses and persistence of the same serum proinflammatory molecules used as diagnostic biomarkers and therapeutic targets for chronic inflammation in humans. Surprisingly, we found long-term persistence of an inflammation-associated neutrophil cell population constitutively producing the proinflammatory IFN-γ cytokine, which until now has only been detected transiently in acute inflammatory responses. Interestingly, these cells appear to confer T cell resistance to the otherwise potent anti-inflammatory function of myeloid-derived suppressor cells, revealing a novel mechanism for the maintenance of chronic inflammatory responses over time. This discovery represents an attractive target to resolve inflammation and prevent the inflammation-induced pathologies that are of critical concern for the well-being of the aging population.

Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

PubMed

Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

2015-04-01

Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

Omega-3 Fatty Acids Attenuate Brain Alterations in High-Fat Diet-Induced Obesity Model.

PubMed

de Mello, Aline Haas; Schraiber, Rosiane de Bona; Goldim, Mariana Pereira de Souza; Garcez, Michelle Lima; Gomes, Maria Luiza; de Bem Silveira, Gustavo; Zaccaron, Rubya Pereira; Schuck, Patrícia Fernanda; Budni, Josiane; Silveira, Paulo Cesar Lock; Petronilho, Fabricia; Rezin, Gislaine Tezza

2018-05-04

This study evaluated the effects of omega-3 on inflammation, oxidative stress, and energy metabolism parameters in the brain of mice subjected to high-fat diet-induced obesity model. Body weight and visceral fat weight were evaluated as well. Male Swiss mice were divided into control (purified low-fat diet) and obese (purified high-fat diet). After 6 weeks, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + OMEGA-3. Fish oil (400 mg/kg/day) or saline solution was administrated orally, during 4 weeks. When the experiment completed 10 weeks, the animals were euthanized and the brain and visceral fat were removed. The brain structures (hypothalamus, hippocampus, prefrontal cortex, and striatum) were isolated. Treatment with omega-3 had no effect on body weight, but reduced the visceral fat. Obese animals showed increased inflammation, increased oxidative damage, decreased antioxidant enzymes activity and levels, changes in the Krebs cycle enzyme activities, and inhibition of mitochondrial respiratory chain complexes in the brain structures. Omega-3 treatment partially reversed the changes in the inflammatory and in the oxidative damage parameters and attenuated the alterations in the antioxidant defense and in the energy metabolism (Krebs cycle and mitochondrial respiratory chain). Omega-3 had a beneficial effect on the brain of obese animals, as it partially reversed the changes caused by the consumption of a high-fat diet and consequent obesity. Our results support studies that indicate omega-3 may contribute to obesity treatment.

Combining eicosapentaenoic acid, decosahexaenoic acid and arachidonic acid, using a fully crossed design, affect gene expression and eicosanoid secretion in salmon head kidney cells in vitro.

PubMed

Holen, Elisabeth; He, Juyun; Espe, Marit; Chen, Liqiou; Araujo, Pedro

2015-08-01

Future feed for farmed fish are based on untraditional feed ingredients, which will change nutrient profiles compared to traditional feed based on marine ingredients. To understand the impact of oils from different sources on fish health, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were added to salmon head kidney cells, in a fully crossed design, to monitor their individual and combined effects on gene expression. Exposing salmon head kidney cells to single fatty acids, arachidonic acid (AA) or decosahexaenoic acid (DHA), resulted in down-regulation of cell signaling pathway genes and specific fatty acid metabolism genes as well as reduced prostaglandin E2 (PGE2) secretion. Eicosapentaenoic acid (EPA) had no impact on gene transcription in this study, but reduced the cell secretion of PGE2. The combined effect of AA + EPA resulted in up-regulation of eicosanoid pathway genes and the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), Bclx (an inducer of apoptosis) and fatty acid translocase (CD36) as well as increased cell secretion of PGE2 into the media. Adding single fatty acids to salmon head kidney cells decreased inflammation markers in this model. The combination AA + EPA acted differently than the rest of the fatty acid combinations by increasing the inflammation markers in these cells. The concentration of fatty acid used in this experiment did not induce any lipid peroxidation responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of intestinal inflammation as an early event in obesity and insulin resistance

PubMed Central

Ding, Shengli; Lund, Pauline K.

2013-01-01

Purpose of review To highlight recent evidence supporting a concept that intestinal inflammation is a mediator or contributor to development of obesity and insulin resistance. Recent findings Current views suggest that obesity-associated systemic and adipose tissue inflammation promote insulin resistance, which underlies many obesity-linked health risks. Diet-induced changes in gut microbiota also contribute to obesity. Recent findings support a concept that high fat diet and bacteria interact to promote early inflammatory changes in the small intestine that contribute to development of or susceptibility to obesity and insulin resistance. This review summarizes the evidence supporting a role of intestinal inflammation in diet-induced obesity and insulin resistance and discusses mechanisms. Summary The role of diet-induced intestinal inflammation as an early biomarker and mediator of obesity, and insulin resistance warrants further study. PMID:21587067

Low-grade inflammation decreases emotion recognition - Evidence from the vaccination model of inflammation.

PubMed

Balter, Leonie J T; Hulsken, Sasha; Aldred, Sarah; Drayson, Mark T; Higgs, Suzanne; Veldhuijzen van Zanten, Jet J C S; Raymond, Jane E; Bosch, Jos A

2018-05-06

The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean age = 25, SD = 5 years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6 h 30 m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (p < .001), without fever, sickness symptoms (e.g., nausea, light-headedness), or mood changes (all p's > .21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (p < .05). RMET stimuli selected on valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression. Copyright © 2018 Elsevier Inc. All rights reserved.

Sandalwood Album Oil as a Botanical Therapeutic in Dermatology.

PubMed

Moy, Ronald L; Levenson, Corey

2017-10-01

Many skin conditions and diseases are characterized by inflammation, infection, and hyperplasia. Safe and effective topical treatment options that can be used long-term are needed. Traditional botanical medicines, which are often complex mixtures that exert their biological activities via multiple mechanisms of action, are being studied as potential new active ingredients in dermatology. Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is an essential oil distilled from the Santalum album tree and has demonstrated biological activity as an anti-inflammatory, anti-microbial, and anti-proliferative agent. Sandalwood album oil has also shown promise in clinical trials for treatment of acne, psoriasis, eczema, common warts, and molluscum contagiosum. The favorable safety profile, ease of topical use, and recent availability of pharmaceutical-grade sandalwood album oil support its broader use as the basis of novel therapies in dermatology.

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.

PubMed

Ramalho, Theresa Raquel de Oliveira; Oliveira, Maria Talita Pacheco de; Lima, Ana Luisa de Araujo; Bezerra-Santos, Claudio Roberto; Piuvezam, Marcia Regina

2015-09-01

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. Georg Thieme Verlag KG Stuttgart · New York.

Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS.

PubMed

Sharma, Ashok Kumar; Bharti, Saurabh; Bhatia, Jagriti; Nepal, Saroj; Malik, Salma; Ray, Ruma; Kumari, Santosh; Arya, Dharamvir Singh

2012-11-01

Increased oxidative stress and inflammation in obesity are the central and causal components in the pathogenesis and progression of cardiometabolic syndrome (CMetS). The aim of the study was to determine the potential role of sesamol (a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil) in chronic high-cholesterol/high-fat diet (HFD)-induced CMetS in rats and to explore the molecular mechanism driving this activity. Rats were fed with HFD (55% calorie from fat and 2% cholesterol) for 60 days to induce obesity, dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the 30th day, rats with total cholesterol >150 mg/dl were considered hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia, dyslipidemia, TNF-α, IL-6, leptin, resistin, highly sensitive C-reactive protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with normalization of adiponectin, nitric oxide and arterial pressures in a dose-dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant enzyme activities were also amended in HFD rats. Similarly, sesamol normalized hepatic steatosis and ultrastructural pathological alteration in hepatocytes, although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic PPARγ, PPARα and e-NOS protein expressions were increased, whereas LXRα, SERBP-1c, P-JNK and NF-κB expression were decreased by sesamol treatment. These results suggest that sesamol attenuates oxidative stress, inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via modulating PPARγ, NF-κB, P-JNK, PPARα, LXRα, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS. Copyright © 2012 Elsevier Inc. All rights reserved.

Oral omega-3 fatty acids promote resolution in chemical peritonitis.

PubMed

Chacon, Alexander C; Phillips, Brett E; Chacon, Miranda A; Brunke-Reese, Deborah; Kelleher, Shannon L; Soybel, David I

2016-11-01

Recent studies suggest that purified omega-3 fatty acids may attenuate acute inflammation and hasten the transition to healing. In this study, we tested the hypothesis that pretreatment with omega-3-rich fish oil (FO) would promote resolution of peritoneal inflammation through production of specific lipid mediators. C57/BL6 mice were given a daily 200-μL oral gavage of saline (CTL) or FO (1.0-1.5 g/kg/d docosahexaenoic acid and 1.3-2.0 g/kg/d eicosapentaenoic acid) for 7 d before chemical peritonitis was induced with thioglycollate. Peritoneal lavage fluid was collected before induction and at days 2 and 4 after peritonitis onset. Prostaglandin E2 (PGE2), Leukotriene B4 (LTB4), Resolvin D1 (RvD1), and the composition of immune cell populations were examined in peritoneal lavage exudates. Cells harvested from the peritoneum were assessed for macrophage differentiation markers, phagocytosis, and lipopolysaccharide-induced cytokine secretion profiles (interleukin [IL]-6, IL-10, IL-1β, TNFα). The ratio of RvD1 to pro-inflammatory PGE2 and LTB4 was increased in the peritoneal cavity of FO-supplemented animals. FO induced a decrease in the number of monocytes in the lavage fluid, with no change in the number of macrophages, neutrophils, or lymphocytes. Macrophage phagocytosis and M1/M2 messenger RNA markers were unchanged by FO with the exception of decreased PPARγ expression. FO increased ex vivo TNFα secretion after stimulation with lipopolysaccharide. Our findings provide evidence that nutraceutically relevant doses of FO supplements given before and during chemical peritonitis shift the balance of lipid mediators towards a proresolution, anti-inflammatory state without drastically altering the number or phenotype of local innate immune cell populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats.

PubMed

Tabassum, Rizwana; Vaibhav, Kumar; Shrivastava, Pallavi; Khan, Andleeb; Ahmed, Mohd Ejaz; Ashafaq, Mohammad; Khan, M Badruzzaman; Islam, Farah; Safhi, Mohammed M; Islam, Fakhrul

2015-01-15

Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia-reperfusion (I-R) injury, this study was designed to elucidate the potential effects of PA against I-R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2h followed by 22h reperfusion in Wistar male rats (250-280g, 14-16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I-R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1β, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I-R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient. Copyright © 2014 Elsevier B.V. All rights reserved.

FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

PubMed Central

Wang, Feng; Cai, Bing; Li, Kai-Cheng; Hu, Xu-Ye; Lu, Ying-Jin; Wang, Qiong; Bao, Lan; Zhang, Xu

2015-01-01

Na+,K+-ATPase (NKA) is required to generate the resting membrane potential in neurons. Nociceptive afferent neurons express not only the α and β subunits of NKA but also the γ subunit FXYD2. However, the neural function of FXYD2 is unknown. The present study shows that FXYD2 in nociceptive neurons is necessary for maintaining the mechanical allodynia induced by peripheral inflammation. FXYD2 interacted with α1NKA and negatively regulated the NKA activity, depolarizing the membrane potential of nociceptive neurons. Mechanical allodynia initiated in FXYD2-deficient mice was abolished 4 days after inflammation, whereas it persisted for at least 3 weeks in wild-type mice. Importantly, the FXYD2/α1NKA interaction gradually increased after inflammation and peaked on day 4 post inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission. Thus, the increased FXYD2 activity may be a fundamental mechanism underlying the persistent hypersensitivity to pain induced by inflammation. PMID:25633594

Fish Oil Accelerates Diet-Induced Entrainment of the Mouse Peripheral Clock via GPR120

PubMed Central

Itokawa, Misa; Nagahama, Hiroki; Ohtsu, Teiji; Furutani, Naoki; Kamagata, Mayo; Yang, Zhi-Hong; Hirasawa, Akira; Tahara, Yu; Shibata, Shigenobu

2015-01-01

The circadian peripheral clock is entrained by restricted feeding (RF) at a fixed time of day, and　insulin secretion regulates RF-induced entrainment of the peripheral clock in mice. Thus, carbohydrate-rich food may be ideal for facilitating RF-induced entrainment, although the role of dietary oils in insulin secretion and RF-induced entrainment has not been described. The soybean oil component of standard mouse chow was substituted with fish or soybean oil containing docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Tuna oil (high DHA/EPA), menhaden oil (standard), and DHA/EPA dissolved in soybean oil increased insulin secretion and facilitated RF-induced phase shifts of the liver clock as represented by the bioluminescence rhythms of PER2::LUCIFERASE knock-in mice. In this model, insulin depletion blocked the effect of tuna oil and fish oil had no effect on mice deficient for GPR120, a polyunsaturated fatty acid receptor. These results suggest food containing fish oil or DHA/EPA is ideal for adjusting the peripheral clock. PMID:26161796

Meibomian Gland Dysfunction and Treatment (Posterior Blepharitis)

MedlinePlus

... if left untreated, MGD can cause or exacerbate dry eye symptoms and eyelid inflammation. The oil glands become ... in permanent changes in the tear film and dry eyes. Symptoms include: ... Stickiness/ Crustiness Watering ...

MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea

PubMed Central

Chen, Yanfeng; Yang, Wenzhao; Zhang, Xiaobo; Yang, Shu; Peng, Gao; Wu, Ting; Zhou, Yueping; Huang, Caihong; Reinach, Peter S.; Li, Wei; Liu, Zuguo

2016-01-01

MK2 activation by p38 MAPK selectively induces inflammation in various diseases. We determined if a MK2 inhibitor (MK2i), improves cornea wound healing by inhibiting inflammation caused by burning rat corneas with alkali. Our study, for the first time, demonstrated that MK2i inhibited alkali burn-induced MK2 activation as well as rises in inflammation based on: a) blunting rises in inflammatory index, inflammatory cell infiltration, ED1+ macrophage and PMN+ neutrophil infiltration; b) suppressing IL-6 and IL-1β gene expression along with those of macrophage inflammatory protein-1α (MIP-1α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); c) reducing angiogenic gene expression levels and neovascularization (NV) whereas anti-angiogenic PEDF levels increased. In addition, this study found that MK2i did not affect human corneal epithelial cell (HCEC) proliferation and migration and had no detectable side effects on ocular surface integrity. Taken together, MK2i selectively inhibited alkali burn-induced corneal inflammation by blocking MK2 activation, these effects have clinical relevance in the treatment of inflammation related ocular surface diseases. PMID:27329698

Dysregulated IL-1β Secretion in Autoinflammatory Diseases: A Matter of Stress?

PubMed Central

Carta, Sonia; Semino, Claudia; Sitia, Roberto; Rubartelli, Anna

2017-01-01

Infectious and sterile inflammation is induced by activation of innate immune cells. Triggering of toll-like receptors by pathogen-associated molecular pattern or damage-associated molecular pattern (PAMP or DAMP) molecules generates reactive oxygen species that in turn induce production and activation of pro-inflammatory cytokines such as IL-1β. Recent evidence indicates that cell stress due to common events, like starvation, enhanced metabolic demand, cold or heat, not only potentiates inflammation but may also directly trigger it in the absence of PAMPs or DAMPs. Stress-mediated inflammation is also a common feature of many hereditary disorders, due to the proteotoxic effects of mutant proteins. We propose that harmful mutant proteins can induce dysregulated IL-1β production and inflammation through different pathways depending on the cell type involved. When expressed in professional inflammatory cells, stress induced by the mutant protein activates in a cell-autonomous way the onset of inflammation and mediates its aberrant development, resulting in the explosive responses that hallmark autoinflammatory diseases. When expressed in non-immune cells, the mutant protein may cause the release of transcellular stress signals that trigger and propagate inflammation. PMID:28421072

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

PubMed

Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

2015-02-01

We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

Emodin mitigates diesel exhaust particles-induced increase in airway resistance, inflammation and oxidative stress in mice.

PubMed

Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2015-08-15

Clinical and experimental studies have reported that short-term exposure to particulate air pollution is associated with inflammation, oxidative stress and impairment of lung function. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has a strong antioxidant and anti-inflammatory actions. Therefore, in the present study, we evaluated the possible ameliorative effect of emodin on diesel exhaust particles (DEP)-induced impairment of lung function, inflammation and oxidative stress in mice. Mice were intratracheally instilled with DEP (20 μg/mouse) or saline (control). Emodin was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty-four hours following DEP exposure, we evaluated airway resistance measured by forced oscillation technique, lung inflammation and oxidative stress. Emodin treatment abated the DEP-induced increase in airway resistance, and prevented the influx of neutrophils in bronchoalveolar lavage fluid. Similarly, lung histopathology confirmed the protective effect of emodin on DEP-induced lung inflammation. DEP induced a significant increase of proinflammatory cytokines in the lung including tumor necrosis factor α, interleukin 6 and interleukin 1β. The latter effect was significantly ameliorated by emodin. DEP caused a significant increase in lung lipid peroxidation, reactive oxygen species and a significant decrease of reduced glutathione concentration. These effects were significantly mitigated by emodin. We conclude that emodin significantly mitigated DEP-induced increase of airway resistance, lung inflammation and oxidative stress. Pending further pharmacological and toxicological studies, emodin may be considered a potentially useful pulmonary protective agent against particulate air pollution-induced lung toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity.

PubMed

Morari, Joseane; Anhe, Gabriel F; Nascimento, Lucas F; de Moura, Rodrigo F; Razolli, Daniela; Solon, Carina; Guadagnini, Dioze; Souza, Gabriela; Mattos, Alexandre H; Tobar, Natalia; Ramos, Celso D; Pascoal, Vinicius D; Saad, Mario J; Lopes-Cendes, Iscia; Moraes, Juliana C; Velloso, Licio A

2014-11-01

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Spinal Actions of Lipoxin A4 and 17(R)-Resolvin D1 Attenuate Inflammation-Induced Mechanical Hypersensitivity and Spinal TNF Release

PubMed Central

Abdelmoaty, Sally; Wigerblad, Gustaf; Bas, Duygu B.; Codeluppi, Simone; Fernandez-Zafra, Teresa; El-Awady, El-Sayed; Moustafa, Yasser; Abdelhamid, Alaa El-din S.; Brodin, Ernst; Svensson, Camilla I.

2013-01-01

Lipoxins and resolvins have anti-inflammatory and pro-resolving actions and accumulating evidence indicates that these lipid mediators also attenuate pain-like behavior in a number of experimental models of inflammation and tissue injury-induced pain. The present study was undertaken to assess if spinal administration of lipoxin A4 (LXA4) or 17 (R)-resolvin D1 (17(R)-RvD1) attenuates mechanical hypersensitivity in the carrageenan model of peripheral inflammation in the rat. Given the emerging role of spinal cytokines in the generation and maintenance of inflammatory pain we measured cytokine levels in the cerebrospinal fluid (CSF) after LXA4 or 17(R)-RvD1 administration, and the ability of these lipid metabolites to prevent stimuli-induced release of cytokines from cultured primary spinal astrocytes. We found that intrathecal bolus injection of LXA4 and17(R)-RvD1 attenuated inflammation-induced mechanical hypersensitivity without reducing the local inflammation. Furthermore, both LXA4 and 17(R)-RvD1 reduced carrageenan-induced tumor necrosis factor (TNF) release in the CSF, while only 17(R)-RvD1attenuated LPS and IFN-γ-induced TNF release in astrocyte cell culture. In conclusion, this study demonstrates that lipoxins and resolvins potently suppress inflammation-induced mechanical hypersensitivity, possibly by attenuating cytokine release from spinal astrocytes. The inhibitory effect of lipoxins and resolvins on spinal nociceptive processing puts them in an intriguing position in the search for novel pain therapeutics. PMID:24086560

In vitro and in vivo antimalarial activity of essential oils and chemical components from three medicinal plants found in northeastern Brazil.

PubMed

Mota, Magaly L; Lobo, Lis Tavares Coelho; Costa, José M Galberto da; Costa, Leandro S; Rocha, Hugo A O; Rocha e Silva, Luiz F; Pohlit, Adrian M; Neto, Valter F de Andrade

2012-05-01

The prophylactic and therapeutic arsenal against malaria is quite restricted and all the antimalarials currently in use have limitations. Thus, there is a need to investigate medicinal plants in the search for phytochemicals which can be developed into drugs. In our investigation, essential oils (EOs) were obtained from Vanillosmopsis arborea (Gardner) Baker, Lippia sidoides Cham. and Croton zehntneri Pax & K. Hoffm., aromatic plants abundant in northeastern Brazil, which are found in the caatinga region and are used in traditional medicine. The chemical composition of these EOs was characterized by GC-MS, and monoterpenes and sesquiterpenes were well represented. We assessed the in vitro activity of these EOs and also individual EO chemical components against the human malaria parasite Plasmodium falciparum (K1 strain) and the in vivo activity of EOs in mice infected with Plasmodium berghei. The acute toxicity of these oils was assessed in healthy mice and in vitro cytotoxicity was determined at different concentrations against HeLa cells and mice macrophages. The EO of V. Arborea was partially active only when using the subcutaneous route (inhibited from 33 up to 47 %). In relation to the EOs, L. sidoides and C. zehntneri were active only by the oral route (per gavage) and partially inhibited the growth of P. berghei from 43 up to 55 % and showed good activity against P. falciparum in vitro (IC (50) = 7.00, 10.50, and 15.20 µg/mL, respectively). Individual EO constituents α-bisabolol, estragole, and thymol also exhibited good activity against P. falciparum (IC (50) = 5.00, 30.70, and 4.50 µg/mL, respectively). This is the first study showing evidence for the antimalarial activity of these species from northeastern Brazil and the low toxicity of their EOs. © Georg Thieme Verlag KG Stuttgart · New York.

Inflammation, oxidative stress and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats.

PubMed

Elswefy, Sahar El-Sayed; Abdallah, Fatma Rizk; Atteia, Hebatallah Husseini; Wahba, Alaa Samir; Hasan, Rehab Abdallah

2016-10-01

Bisphenol A (BPA) is a key monomer in the production of plastics. It has been shown to be hepatotoxic. Inflammation and oxidative stress are closely linked with liver fibrosis, the major contributing factor to hepatic failure. Therefore, the aim of this study was to evaluate the impact of chronic exposure to BPA on the development of hepatic fibrosis in male rats and to determine the cross-talk between the hepatic cytokine network, oxidative stress and apoptosis. For this purpose, 30 male Wistar albino rats were divided into three equal groups as follows: the first group was given no treatment (normal control group); the second group was given corn oil once daily by oral gavage for 8 weeks (vehicle control group); and the third group received BPA (50 mg/kg body weight/day, p.o.) for 8 weeks. BPA administration induced liver fibrosis as reflected in an increase in serum hepatic enzymes activities, hepatic hydroxyproline content and histopathological changes particularly increased collagen fibre deposition around the portal tract. In addition, there was inflammation (as reflected in increase in interleukin-1beta 'IL-1β', decrease in interleukin-10 'IL-10' serum levels and increase in IL-1β/IL-10 ratio), oxidative stress (as reflected in increase in malondialdehyde (MDA) level, reduction in reduced glutathione (GSH) content and inhibition of catalase (CAT) activity) and apoptosis [as reflected in an increase in caspase-3 level and a decrease in numbers of B-cell lymphoma 2 (BCL2)-immunopositive hepatocytes]. Interestingly, BPA had an upregulating effect on an extracellular matrix turnover gene [as reflected in matrix metalloproteinase-9 (MMP-9)] and a downregulating effect on its inhibitor gene [as reflected in tissue inhibitor of matrix metalloproteinase-2 (TIMP-2)] expression. Thus, the mechanism by which BPA induced liver fibrosis seems to be related to stimulation of the inflammatory response, along with oxidative stress, the apoptotic pathway and activation of extracellular matrix turnover. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation.

PubMed

Bosquet, Alba; Girona, Josefa; Guaita-Esteruelas, Sandra; Heras, Mercedes; Saavedra-García, Paula; Martínez-Micaelo, Neus; Masana, Lluís; Rodríguez-Calvo, Ricardo

2018-06-01

Fatty acid binding protein 4 (FABP4) inhibitors have been proposed as potential therapeutic approaches against insulin resistance-related inflammation and type 2 diabetes mellitus. However, the underlying molecular mechanisms by which these molecules drive these effects in skeletal muscle remain unknown. Here, we assessed whether the FABP4 inhibitor BMS309403 prevented lipid-induced endoplasmic reticulum (ER) stress-associated inflammation in skeletal muscle. The BMS309403 treatment was assessed both in the skeletal muscle of high-fat diet (HFD)-fed mice and in palmitate-stimulated C2C12 myotubes. HFD feeding promoted insulin resistance, which is characterized by increased plasma levels of glucose, insulin, non-esterified fatty acids, triglycerides, resistin, and leptin and reduced plasma levels of adiponectin compared with control mice fed a standard diet. Additionally, insulin-resistant animals showed increased FABP4 plasma levels. In line with this evidence, recombinant FABP4 attenuated the insulin-induced AKT phosphorylation in C2C12 myotubes. Treatment with BMS309403 reduced lipid-induced ER stress and inflammation in both mouse skeletal muscle and C2C12 myotubes. The effects of the FABP4 inhibitor reducing lipid-induced ER stress-associated inflammation were related to the reduction of fatty acid-induced intramyocellular lipid deposits, ROS and nuclear factor-kappaB (NF-κB) nuclear translocation. Accordingly, BMS309403 reduced lipid-induced p38 MAPK phosphorylation, which is upstream of NF-κB activation. Overall, these findings indicate that BMS309403 reduces fatty acid-induced ER stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation. Copyright © 2018 Elsevier B.V. All rights reserved.

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

PubMed

Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Effects of positive end-expiratory pressure titration and recruitment maneuver on lung inflammation and hyperinflation in experimental acid aspiration-induced lung injury.

PubMed

Ambrosio, Aline M; Luo, Rubin; Fantoni, Denise T; Gutierres, Claudia; Lu, Qin; Gu, Wen-Jie; Otsuki, Denise A; Malbouisson, Luiz M S; Auler, Jose O C; Rouby, Jean-Jacques

2012-12-01

In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.