Anti-inflammatory and cytotoxic activities of Bursera copallifera.

PubMed

Columba-Palomares, M F María C; Villareal, Dra María L; Acevedo Quiroz, M C Macdiel E; Marquina Bahena, M C Silvia; Álvarez Berber, Dra Laura P; Rodríguez-López, Dra Verónica

2015-10-01

The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain. The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 μg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 μg/mL, IC50 = 5.7 μg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 μg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 μg/mL), whereas DMeL exhibited an IC50 value of 19.9 μg/mL. In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera.

Anti-inflammatory actions of clonidine, guanfacine and B-HT 920 against various inflammagen-induced acute paw oedema in rats.

PubMed

Kulkarni, S K; Mehta, A K; Kunchandy, J

1986-02-01

Clonidine (0.1-1.0 mg/kg, i.p.) exhibited anti-inflammatory activity in carrageenan-, formalin-, 5-HT- and histamine-induced paw oedema in rats. Similarly, other two alpha 2-adrenoceptor agonists, guanfacine and B-HT 920, also displayed an anti-inflammatory action in these models. The anti-inflammatory effect of all the three alpha 2-adrenoceptor agonists was reversed by yohimbine. However, prazosin failed to block the anti-inflammatory effect of clonidine. Intracerebroventricularly administered clonidine had a delayed onset of anti-inflammatory action, starting only from 60 min post carrageenan administration. This was in contrast to the systemically administered clonidine which was effective against both phases of carrageenan-induced oedema. On the other hand, irrespective of the route of administration, i.e. peripheral or central, guanfacine and B-HT 920 were effective against the early as well as against the delayed phases of the inflammatory reaction. The studies suggest that it is not the imidazoline moiety but the activation of alpha 2-adrenoceptors which is essential for the anti-inflammatory action of these agents.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

PubMed

Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

2012-11-01

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

6-Gingerol inhibits ROS and iNOS through the suppression of PKC-{alpha} and NF-{kappa}B pathways in lipopolysaccharide-stimulated mouse macrophages

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

Lee, Tzung-Yan, E-mail: joyamen@mail.cgu.edu.tw; Lee, Ko-Chen; Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

2009-04-24

Inflammation is involved in numerous diseases, including chronic inflammatory diseases and the development of cancer. Many plants possess a variety of biological activities, including antifungal, antibacterial and anti-inflammatory activities. However, our understanding of the anti-inflammatory effects of 6-gingerol is very limited. We used lipopolysaccharide (LPS)-stimulated macrophages as a model of inflammation to investigate the anti-inflammatory effects of 6-gingerol, which contains phenolic structure. We found that 6-gingerol exhibited an anti-inflammatory effect. 6-Gingerol could decrease inducible nitric oxide synthase and TNF-{alpha} expression through suppression of I-{kappa}B{alpha} phosphorylation, NF-{kappa}B nuclear activation and PKC-{alpha} translocation, which in turn inhibits Ca{sup 2+} mobilization and disruptionmore » of mitochondrial membrane potential in LPS-stimulated macrophages. Here, we demonstrate that 6-gingerol acts as an anti-inflammatory agent by blocking NF-{kappa}B and PKC signaling, and may be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.« less

Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice.

PubMed

Fialho, Maria Fernanda Pessano; Brusco, Indiara; da Silva Brum, Evelyne; Piana, Mariana; Boligon, Aline Augusti; Trevisan, Gabriela; Oliveira, Sara Marchesan

2017-08-17

Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Buddleja thyrsoides Lam., known as 'Barbasco' or 'Cambara', is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25-30 g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides extract crude revealed the presence of the lupeol, stigmasterol, and β-sitosterol. The stability study of the B. thyrsoides gel did not show relevant changes at low temperatures. The oral treatment with the B. thrysoides extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The B. thyrsoides antinociceptive effect was not reversed by naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition ( I max ) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with B. thyrsoides did not cause adverse effects. These findings suggest that the oral or topical treatment with B. thyrsoides presents antinociceptive actions in an arthritic pain model without causing adverse effects. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation

PubMed Central

Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

2015-01-01

Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification. PMID:26347154

Phytochemical Composition, Antioxidant, Antimicrobial and in Vivo Anti-inflammatory Activity of Traditionally Used Romanian Ajuga laxmannii (Murray) Benth. (“Nobleman’s Beard” – Barba Împăratului)

PubMed Central

Toiu, Anca; Mocan, Andrei; Vlase, Laurian; Pârvu, Alina E.; Vodnar, Dan C.; Gheldiu, Ana-Maria; Moldovan, Cadmiel; Oniga, Ilioara

2018-01-01

In the Romanian folk medicine, aerial parts of Ajuga laxmannii (“nobleman’s beard,” Romanian – “barba boierului” or “avrămească” or “creştinească”) are traditionally used as galactagogue and anti-inflammatory agents. The present study aimed to evaluate the chemical composition (polyphenols, iridoids, and phytosterols), antioxidant, antimicrobial and in vivo anti-inflammatory activity of different extracts of A. laxmannii aerial parts. The major identified bioactive compounds were rutin, 8-O-acetylharpagide and β-sitosterol. The antioxidant activity of A. laxmannii extracts was evaluated using several methods, and the results showed good antiradical effects. Moreover, the antimicrobial evaluation showed a potent antifungal activity against C. albicans and P. funiculosum. Furthermore, the anti-inflammatory effect was determined by monitoring some parameters involved in the inflammatory process. The results obtained showed differences between the analyzed extracts; and therefore the importance of choosing the best solvent in order to extract the appropriate amount of bioactive compounds. A. laxmannii ethanol extract showed an anti-inflammatory effect by reducing total leukocytes, PMN, phagocytosis, and oxidative stress. Compared to diclofenac, only the 50 mg/mL A. laxmannii extract had better anti-inflammatory and anti-oxidative stress effects, and this could justify the importance of a correlation between the activity and the used concentration. These findings strongly suggest that A. laxmannii could be considered as a valuable source of bioactive compounds, which could be further valued as anti-inflammatory agents in the composition of several herbal drugs. PMID:29551972

Cysteine, histidine and glycine exhibit anti-inflammatory effects in human coronary arterial endothelial cells.

PubMed

Hasegawa, S; Ichiyama, T; Sonaka, I; Ohsaki, A; Okada, S; Wakiguchi, H; Kudo, K; Kittaka, S; Hara, M; Furukawa, S

2012-02-01

The activation of nuclear factor-kappa B (NF-κB) in vascular endothelial cells may be involved in vascular pathogeneses such as vasculitis or atherosclerosis. Recently, it has been reported that some amino acids exhibit anti-inflammatory effects. We investigated the inhibitory effects of a panel of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases in various cell types. The activation of NF-κB was determined in human coronary arterial endothelial cells (HCAECs) because NF-κB modulates the production of many cytokines and the expression of adhesion molecules. We examined the inhibitory effects of the amino acids cysteine, histidine and glycine on the induction of NF-κB activation, expression of CD62E (E-selectin) and the production of interleukin (IL)-6 in HCAECs stimulated with tumour necrosis factor (TNF)-α. Cysteine, histidine and glycine significantly reduced NF-κB activation and inhibitor κBα (IκBα) degradation in HCAECs stimulated with TNF-α. Additionally, all the amino acids inhibited the expression of E-selectin and the production of IL-6 in HCAECs, and the effects of cysteine were the most significant. Our results show that glycine, histidine and cysteine can inhibit NF-κB activation, IκBα degradation, CD62E expression and IL-6 production in HCAECs, suggesting that these amino acids may exhibit anti-inflammatory effects during endothelial inflammation. © 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders

PubMed Central

Johnson, Tyler A.; Sohn, Johann; Inman, Wayne D.; Bjeldanes, Leonard F.; Rayburn, Keith

2012-01-01

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica, (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activity in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves were also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with the standard anti-inflammatory agent celastrol (1) but was moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves plant portions displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects ≥ 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of the roots, stems or leaves of stinging nettle may be more effective then traditional tinctures (water, methanol, ethanol) to undergo clinical evaluations for the treatment of inflammatory disorders including arthritis. A chemical investigation into the lipophillic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. PMID:23092723

Synthesis and Biological Evaluation of New Natural Phenolic (2E,4E,6E)-Octa-2,4,6-trienoic Esters.

PubMed

Gandolfi, Raffaella; Contini, Alessandro; Pinto, Daniela; Marzani, Barbara; Pandini, Stefano; Nava, Donatella; Pini, Elena

2017-12-01

In the present study the esterification of the OH groups of resveratrol, caffeic acid, ferulic acid, and β-sitosterol with an antioxidant polyconjugated fatty acid, (2E,4E,6E)-octa-2,4,6-trienoic acid, was achieved. As the selective esterification of OH groups of natural compounds can affect their biological activity, a selective esterification of resveratrol and caffeic acid was performed by an enzymatic approach. The new resulting compounds were characterized spectroscopically (FT-IR, NMR mono, and bidimensional techniques); when necessary the experimental data were integrated by quantum chemical calculations. The antioxidant, anti-inflammatory and proliferative activity was evaluated. The good results encourage the use of these molecules as antioxidant and/or anti-inflammatory agents in dermocosmetic application. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Terpenoids from Platostoma rotundifolium (Briq.) A. J. Paton Alter the Expression of Quorum Sensing-Related Virulence Factors and the Formation of Biofilm in Pseudomonas aeruginosa PAO1

PubMed Central

Rasamiravaka, Tsiry; Ngezahayo, Jérémie; Pottier, Laurent; Oliveira Ribeiro, Sofia; Souard, Florence; Hari, Léonard; Stévigny, Caroline; El Jaziri, Mondher; Duez, Pierre

2017-01-01

Platostoma rotundifolium (Briq.) A. J. Paton aerial parts are widely used in Burundi traditional medicine to treat infectious diseases. In order to investigate their probable antibacterial activities, crude extracts from P. rotundifolium were assessed for their bactericidal and anti-virulence properties against an opportunistic bacterial model, Pseudomonas aeruginosa PAO1. Whereas none of the tested extracts exert bacteriostatic and/or bactericidal proprieties, the ethyl acetate and dichloromethane extracts exhibit anti-virulence properties against Pseudomonas aeruginosa PAO1 characterized by an alteration in quorum sensing gene expression and biofilm formation without affecting bacterial viability. Bioguided fractionation of the ethyl acetate extract led to the isolation of major anti-virulence compounds that were identified from nuclear magnetic resonance and high-resolution molecular spectroscopy spectra as cassipourol, β-sitosterol and α-amyrin. Globally, cassipourol and β-sitosterol inhibit quorum sensing-regulated and -regulatory genes expression in las and rhl systems without affecting the global regulators gacA and vfr, whereas α-amyrin had no effect on the expression of these genes. These terpenoids disrupt the formation of biofilms at concentrations down to 12.5, 50 and 50 µM for cassipourol, β-sitosterol and α-amyrin, respectively. Moreover, these terpenoids reduce the production of total exopolysaccharides and promote flagella-dependent motilities (swimming and swarming). The isolated terpenoids exert a wide range of inhibition processes, suggesting a complex mechanism of action targeting P. aeruginosa virulence mechanisms which support the wide anti-infectious use of this plant species in traditional Burundian medicine. PMID:28613253

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders.

PubMed

Johnson, Tyler A; Sohn, Johann; Inman, Wayne D; Bjeldanes, Leonard F; Rayburn, Keith

2013-01-15

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. Published by Elsevier GmbH.

Potent Anti-Inflammatory Activity of Ursolic Acid, a Triterpenoid Antioxidant, Is Mediated through Suppression of NF-κB, AP-1 and NF-AT

PubMed Central

Checker, Rahul; Sandur, Santosh K.; Sharma, Deepak; Patwardhan, Raghavendra S.; Jayakumar, S.; Kohli, Vineet; Sethi, Gautam; Aggarwal, Bharat B.; Sainis, Krishna B.

2012-01-01

Background Ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, is the major component of many plants including apples, basil, cranberries, peppermint, rosemary, oregano and prunes and has been reported to possess antioxidant and anti-tumor properties. These properties of UA have been attributed to its ability to suppress NF-κB (nuclear factor kappa B) activation. Since NF-κB, in co-ordination with NF-AT (nuclear factor of activated T cells) and AP-1(activator protein-1), is known to regulate inflammatory genes, we hypothesized that UA might exhibit potent anti-inflammatory effects. Methodology/Principal Findings The anti-inflammatory effects of UA were assessed in activated T cells, B cells and macrophages. Effects of UA on ERK, JNK, NF-κB, AP-1 and NF-AT were studied to elucidate its mechanism of action. In vivo efficacy of UA was studied using mouse model of graft-versus-host disease. UA inhibited activation, proliferation and cytokine secretion in T cells, B cells and macrophages. UA inhibited mitogen-induced up-regulation of activation markers and co-stimulatory molecules in T and B cells. It inhibited mitogen-induced phosphorylation of ERK and JNK and suppressed the activation of immunoregulatory transcription factors NF-κB, NF-AT and AP-1 in lymphocytes. Treatment of cells with UA prior to allogenic transplantation significantly delayed induction of acute graft-versus-host disease in mice and also significantly reduced the serum levels of pro-inflammatory cytokines IL-6 and IFN-γ. UA treatment inhibited T cell activation even when added post-mitogenic stimulation demonstrating its therapeutic utility as an anti-inflammatory agent. Conclusions/Significance The present study describes the detailed mechanism of anti-inflammatory activity of UA. Further, UA may find application in the treatment of inflammatory disorders. PMID:22363615

Holoptelea integrifolia (Roxb.) Planch: A Review of Its Ethnobotany, Pharmacology, and Phytochemistry

PubMed Central

Ganie, Showkat Ahmad; Yadav, Surender Singh

2014-01-01

Holoptelea integrifolia (Ulmaceae) is a versatile medicinal plant used in various indigenous systems of medicine for curing routine healthcare maladies. It is traditionally used in the treatment and prevention of several ailments like leprosy, inflammation, rickets, leucoderma, scabies, rheumatism, ringworm, eczema, malaria, intestinal cancer, and chronic wounds. In vitro and in vivo pharmacological investigations on crude extracts and isolated compounds showed antibacterial, antifungal, analgesic, antioxidant, anti-inflammatory, anthelmintic, antidiabetic, antidiarrhoeal, adaptogenic, anticancer, wound healing, hepatoprotective, larvicidal, antiemetic, CNS depressant, and hypolipidemic activities. Phytochemical analysis showed the presence of terpenoids, sterols, saponins, tannins, proteins, carbohydrates, alkaloids, phenols, flavonoids, glycosides, and quinines. Numerous compounds including Holoptelin-A, Holoptelin-B, friedlin, epifriedlin, β-amyrin, stigmasterol, β-sitosterol, 1, 4-napthalenedione, betulin, betulinic acid, hexacosanol, and octacosanol have been identified and isolated from the plant species. The results of several studies indicated that H. integrifolia may be used as an effective therapeutic remedy in the prevention and treatment of various ailments. However, further studies on chemical constituents and their mechanisms in exhibiting certain biological activities are needed. In addition, study on the toxicity of the crude extracts and the compounds isolated from this plant should be assessed to ensure their eligibility to be used as source of modern medicines. PMID:24949441

Discovery and evaluation of asymmetrical monocarbonyl analogs of curcumin as anti-inflammatory agents

PubMed Central

Zhang, Yali; Zhao, Chengguang; He, Wenfei; Wang, Zhe; Fang, Qilu; Xiao, Bing; Liu, Zhiguo; Liang, Guang; Yang, Shulin

2014-01-01

Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS) – a component of the cell walls of gram-negative bacteria, via toll-like receptor 4–mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases. PMID:24741294

Marine Diterpenoids as Potential Anti-Inflammatory Agents

PubMed Central

González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

2015-01-01

The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

Assessment of phytochemicals, antioxidant, and anti-inflammatory potential of Boerhavia procumbens Banks ex Roxb.

PubMed

Bokhari, Jasia; Khan, Muhammad Rashid; Haq, Ihsan Ul

2016-08-01

Boerhavia procumbens is traditionally used in the treatment of various disorders including jaundice and gonorrhea, is a refrigerant, and exhibits anti-inflammatory and antispasmodic activities. The purpose of this study was to determine the phytochemical classes, antioxidant and anti-inflammatory activities of methanol extract (BPME) and different fractions (n-hexane (BPHE), ethyl acetate (BPEE), n-butanol (BPBE), and residual aqueous fraction (BPAE)) of B. procumbens against carrageenan-induced paw edema in rats. To assess the anti-inflammatory effects of B. procumbens, 42 Sprague Dawley male rats (150-200 g) were randomly divided into seven groups. Group I received distilled water and group II was treated with diclofenac potassium (10 mg/kg) body weight (bw) orally. Groups III, IV, V, VI, and VII were administered BPME, BPHE, BPEE, BPBE, and BPAE (200 mg/kg bw) orally, 1 h before the treatment with carrageenan (10 mg/kg bw) in rats. Anti-inflammatory effects of B. procumbens were determined by estimating the inhibition of edema at 1st, 2nd, and 3rd hour after carrageenan injection. Qualitative analysis of methanol extract indicated the composition of diverse classes, namely, flavonoids, tannins, saponins, phlobatannins, cardiac glycosides, alkaloids, terpenoids, and anthraquinones. Quantitative determination illustrated that BPBE and BPEE possessed the highest concentration of total phenolic (60.45 ± 2.1 mg gallic acid equivalent per gram sample) and total flavonoid content (68.05 ± 2.3 mg rutin equivalent per gram sample), respectively. A dose-dependent response for antioxidant activity was exhibited by all the samples. The sample with the highest aptitude for antioxidant activity was the BPBE for 2,2-azobis,3-ethylbenzothiozoline-6-sulfonic acid radical scavenging and total antioxidant capacity. Carrageenan-induced paw edema was significantly (p < 0.05) inhibited by BPBE and BPME at the 1st, 2nd, and 3rd hour and was comparable to control drug diclofenac potassium. Results revealed that various fractions of B. procumbens manifested the antioxidant and anti-inflammatory potential and accredit the local use of B. procumbens in various disorders. © The Author(s) 2015.

Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human aortic endothelial cells.

PubMed

Zapolska-Downar, D; Bryk, D; Małecki, M; Hajdukiewicz, K; Sitkiewicz, D

2012-08-01

Altered expression of cell adhesion molecules (CAMs) has been implicated in a variety of chronic inflammatory conditions, including atherosclerosis. Regulation of adhesion molecule expression by specific redox-sensitive mechanisms has been reported. Additionally, it has been observed that the extract of Aronia melanocarpa (A. Melanocarpa) fruits, rich in polyphenols, exhibits potent anti-oxidant properties and displays cardioprotective activity. Human aortic endothelial cells (HAECs) were pretreated with various concentrations (primarily 50 μg/mL) of Aronia Melanocarpa fruit extract prior to treatment with TNFα (10 ng/mL) for various periods of time. The surface protein and mRNA expression of ICAM-1 and VCAM-1 were determined using flow cytometry and real-time RT-PCR, respectively. Adhesion of peripheral blood mononuclear leucocytes (PBMLs) to TNFα-treated HAECs was evaluated by an adhesion assay. Activation of NF-κB was evaluated by measuring NF-κB p65 phosphorylation using flow cytometry. ROS production was determined by reduction in fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). Tested A. Melanocarpa extract significantly inhibited the expression of ICAM-1 and VCAM-1, attenuated the phosphorylation of NF-κB p65 and decreased intracellular ROS production in TNFα-treated HAECs. We conclude that A. Melanocarpa fruit extract exhibits anti-inflammatory effects in HAECs by inhibiting the expression of endothelial CAMs, activation of NF-κB and production of ROS.

Glitazones inhibit human monoamine oxidase but their anti-inflammatory actions are not mediated by VAP-1/semicarbazide-sensitive amine oxidase inhibition.

PubMed

Carpéné, Christian; Bizou, Mathilde; Tréguer, Karine; Hasnaoui, Mounia; Grès, Sandra

2015-09-01

Glitazones are peroxisome proliferator-activated receptor gamma (PPARγ) agonists widely used as antidiabetic drugs also known as thiazolidinediones. Most of them exert other effects such as anti-inflammatory actions via mechanisms supposed to be independent from PPARγ activation (e.g., decreased plasma monocyte chemoattractant protein-1 (MCP-1) levels). Recently, pioglitazone has been shown to inhibit the B form of monoamine oxidase (MAO) in mouse, while rosiglitazone and troglitazone were described as non-covalent inhibitors of both human MAO A and MAO B. Since molecules interacting with MAO might also inhibit semicarbazide-sensitive amine oxidase (SSAO), known as vascular adhesion protein-1 (VAP-1), and since VAP-1/SSAO inhibitors exhibit anti-inflammatory activity, our aim was to elucidate whether VAP-1/SSAO inhibition could be a mechanism involved in the anti-inflammatory behaviour of glitazones. To this aim, MAO and SSAO activities were measured in human subcutaneous adipose tissue biopsies obtained from overweight women undergoing plastic surgery. The production of hydrogen peroxide, an end-product of amine oxidase activity, was determined in tissue homogenates using a fluorometric method. The oxidation of 1 mM tyramine was inhibited by pargyline and almost resistant to semicarbazide, therefore predominantly MAO-dependent. Rosiglitazone was more potent than pioglitazone in inhibiting tyramine oxidation. By contrast, benzylamine oxidation was only abolished by semicarbazide: hence SSAO-mediated. Pioglitazone hampered SSAO activity only when tested at 1 mM while rosiglitazone was inefficient. However, rosiglitazone exhibited anti-inflammatory activity in human adipocytes by limiting MCP-1 expression. Our observations rule out any involvement of VAP-1/SSAO inhibition and subsequent limitation of leukocyte extravasation in the anti-inflammatory action of glitazones.

Inhibition of Nuclear Factor κB Activation and Cyclooxygenase-2 Expression by Aqueous Extracts of Hispanic Medicinal Herbs

PubMed Central

Gonzales, Amanda M.; Hunsaker, Lucy A.; Franco, Carolina R.; Royer, Robert E.; Vander Jagt, David L.; Vander Jagt, Dorothy J.

2010-01-01

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are a primary choice of therapy for diseases with a chronic inflammatory component. Unfortunately, long-term NSAID therapy is often accompanied by severe side effects, including cardiovascular and gastrointestinal complications. Because of this, there is critical need for identification of new and safer treatments for chronic inflammation to circumvent these side effects. Inflammatory diseases have been successfully remedied with natural herbs by many cultures. To better understand the potential of natural herbs in treating chronic inflammation and to identify their mechanism of action, we have evaluated the anti-inflammatory activities of 20 medicinal herbs commonly used in the Hispanic culture. We have established a standardized method for preparing aqueous extracts (teas) from the selected medicinal herbs and screened for inhibition of tumor necrosis factor-α-induced activation of nuclear factor κB (NF-κB), which is the central signaling pathway of the inflammatory response. A number of herbal teas were identified that exhibited significant anti-inflammatory activity. In particular, tea from the herb commonly called laurel was found to be an especially potent inhibitor of NF-κB-dependent cyclooxygenase-2 gene expression and prostaglandin E2 production in cultured murine macrophages. These findings indicate that laurel tea extract contains potent anti-inflammatory compounds that function by inhibiting the major signal transduction pathway responsible for inducing an inflammatory event. Based on these results, laurel may represent a new, safe therapeutic agent for managing chronic inflammation. PMID:20482259

Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways.

PubMed

Jo, Il-Joo; Bae, Gi-Sang; Choi, Sun Bok; Kim, Dong-Goo; Shin, Joon-Yeon; Seo, Seung-Hee; Choi, Mee-Ok; Kim, Tae-Hyeon; Song, Ho-Joon; Park, Sung-Joo

2014-08-15

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells.

PubMed

Hasegawa, Shunji; Ichiyama, Takashi; Sonaka, Ichiro; Ohsaki, Ayami; Hirano, Reiji; Haneda, Yasuhiro; Fukano, Reiji; Hara, Masami; Furukawa, Susumu

2011-11-01

The elemental diet is one of the effective therapies for inflammatory bowel disease. However, the mechanism remains unclear, and there have never been reports about the inhibitory effects of amino acids in human monocytes/macrophages. We investigated the inhibitory effects of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases, in human monocytes/macrophages. We examined the inhibitory effects of cysteine, histidine or glycine on the induction of nuclear factor-κB (NF-κB) activation, expression of intracellular adhesion molecule-1 (ICAM-1, CD54) and production of interleukin-8 (IL-8) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs) stimulated with tumor necrosis factor-α (TNF-α). Cysteine, histidine and glycine significantly reduced the activation of NF-κB in THP-1 cells stimulated with TNF-α. In addition, cysteine and histidine significantly inhibited the expression of ICAM-1 and production of IL-8 in THP-1 cells and PBMCs. Our results suggest that cysteine and histidine exhibit anti-inflammatory effects in THP-1 cells, and may be responsible for the efficacy of treatment in inflammatory bowel diseases.

Design, synthesis, and anti-inflammatory activity of caffeoyl salicylate analogs as NO production inhibitors.

PubMed

Yu, Pan; Xia, Chao-Jie; Li, Dong-Dong; Ni, Jun-Jun; Zhao, Lin-Guo; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei

2018-05-28

Chlorogenic acid (CGA) has been reported to exhibit potent anti-inflammatory activity. However, the development of anti-inflammatory agent based on CGA has not been investigated. In this paper, a series of caffeoyl salicylate compounds derived from CGA were designed, synthesized, and evaluated by LPS-induced nitric oxide synthase inhibition and QRT-PCR technique. Most compounds showed modest activity to inhibit production of nitric oxide (NO) in RAW 264.7 cells induced by lipopolysaccharides (LPS). Among these compounds, QRT-PCR and western blotting results indicated that compounds 6b, 6c, 6f, 6g and D104 that possess 5-member ring or 6-member ring caused a significant inhibition against expression of the iNOS2 in LPS-induced macrophages. In addition, cytotoxic assay displayed most derivatives have good safety in vitro. This new promising scaffold could be further exploited for the development of anti-inflammatory agent in the future. Copyright © 2017. Published by Elsevier B.V.

Amomum tsao-ko suppresses lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages via Nrf2-dependent heme oxygenase-1 expression.

PubMed

Li, Bin; Choi, Hee-Jin; Lee, Dong-Sung; Oh, Hyuncheol; Kim, Youn-Chul; Moon, Jin-Young; Park, Won-Hwan; Park, Sun-Dong; Kim, Jai-Eun

2014-01-01

Amomum tsao-ko Crevost et Lemaire, used as a spice in Asia, is an important source of Chinese cuisine and traditional Chinese medicines. A. tsao-ko is reported to exert a variety of biological and pharmacological activities, including anti-proliferative, anti-oxidative and neuroprotective effects. In this study, NNMBS227, consisting of the ethanol extract of A. tsao-ko, exhibited potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS227 in the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β) in LPS stimulated macrophages. NNMBS227 also inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by stimulation with LPS. In addition, NNMBS227 induced heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we confirmed an association between the anti-inflammatory effects of NNMBS227 and the up-regulation of HO-1. These findings suggest that Nrf2-dependent increases in the expression of HO-1 induced by NNMBS227 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

New Anti-Inflammatory Cembranes from the Cultured Soft Coral Nephthea columnaris

PubMed Central

Hsiao, Ting-Hsi; Sung, Chun-Sung; Lan, Yu-Hsuan; Wang, Yi-Chen; Lu, Mei-Chin; Wen, Zhi-Hong; Wu, Yang-Chang; Sung, Ping-Jyun

2015-01-01

Two new cembranes, columnariols A (1) and B (2), were isolated from the cultured soft coral Nephthea columnaris. The structures of cembranes 1 and 2 were elucidated by spectroscopic methods. In the anti-inflammatory effects test, cembranes 1 and 2 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Compound 1 exhibited moderate cytotoxicity toward LNCaP cells with an IC50 value of 9.80 μg/mL. PMID:26035022

Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation.

PubMed

Zhao, Zhanzhong; Tang, Xiangfang; Zhao, Xinghui; Zhang, Minhong; Zhang, Weijian; Hou, Shaohua; Yuan, Weifeng; Zhang, Hongfu; Shi, Lijun; Jia, Hong; Liang, Lin; Lai, Zhi; Gao, Junfeng; Zhang, Keyu; Fu, Ling; Chen, Wei

2014-07-01

Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1β, PGE2, TNF-α and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IκBα phosphorylation and degradation, and blocked the NF-κB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-κB activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity

PubMed Central

Hua, J; Scott, R.W.; Diamond, G

2011-01-01

Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 µg ml−1 mPE was sufficient to inhibit interleukin-1β-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-κB, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues. PMID:21040516

Nyctanthes arbor-tristis Linn--a critical ethnopharmacological review.

PubMed

Agrawal, Jyoti; Pal, Anirban

2013-04-19

Nyctanthes arbor-tristis (Oleaceae) is a mythological plant; has high medicinal values in Ayurveda. The popular medicinal use of this plant are anti-helminthic and anti-pyretic besides its use as a laxative, in rheumatism, skin ailments and as a sedative. Vitally, the natives plant it in their home gardens to pass on its medicinal usage to oncoming generations. The present review encompasses an ethnopharmacological evaluation focusing on information on the chemical constituents, pharmacological actions and toxicology in order to reveal the therapeutic potential and gaps requiring research involvement. The present review is based on searches in Scifinder(®), Pubmed (National Library of Medicine) and books published on the subject during the period 1933 to 2012. Nyctanthes arbor-tristis is most important in local and traditional medicines especially in India for treating intermittent fevers, arthritis and obstinate sciatica. Crude extracts and isolated compounds from the plant were shown to be pharmacologically active against inflammation, malaria, viral infection, leishmanisis and as an immunostimulant. The major class of biologically active compounds are the iridoid glucosides incl., Arbortristoside A, B and C from the seeds active as anticancer, anti-leishmania, anti-inflammatory, anti-allergic, immunomodulatory and antiviral. Other molecules; calceolarioside A, 4-hydroxyhexahydrobenzofuran-7one and β-sitosterol from leaves have been reported to be active as anti-leishmanial, anticancer and anti-inflammatory, respectively. The crude extracts have been found to be safe with an LD50 of 16gm/kg, while the LD50 of arbortristoside-A isolated from the seeds was found to be 0.5g/kg. Mostly in-vitro or in some cases in-vivo models provide some evidence especially in the treatment of inflammatory conditions like arthritis, fevers related to malaria and protozoan diseases especially leishmaniasis. The only clinical study found, is for treating malaria, but with crude extract only. Further, more detailed safety data pertaining to the acute and sub-acute toxicity, cardio and immunotoxicity also needs to be generated for crude extracts or pure compounds. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.

PubMed

Huang, Mei-Yan; Lin, Jing; Lu, Kuo; Xu, Hong-Gui; Geng, Zhi-Zhong; Sun, Ping-Hua; Chen, Wei-Min

2016-04-13

Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.

Anti-inflammatory steroids from the rhizomes of Dioscorea septemloba Thunb.

PubMed

Zhang, Yi; Yu, Hai-Yang; Chao, Li-Ping; Qu, Lu; Ruan, Jing-Ya; Liu, Yan-Xia; Dong, Yong-Zhe; Han, Li-Feng; Wang, Tao

2016-08-01

Seven new steroid glycosides, dioscorosides A1 (1), A2 (2), B1 (3), B2 (4), C1 (5), C2 (6), and D (7), together with 22 known ones (8-29) were isolated from the rhizomes of Dioscorea septemloba, their structures were elucidated by chemical and spectroscopic methods. All isolates were evaluated for in vitro anti-inflammatory potential using LPS-stimulated RAW 264.7 murine macrophages. Among them, spirostane glycosides 18 and 21-24 exhibited significant inhibition of nitrite production. Moreover, the structure-activity relationship was summarized. Copyright © 2016 Elsevier Inc. All rights reserved.

Coumarins from the roots of Angelica dahurica cause anti-allergic inflammation

PubMed Central

Li, Dong; Wu, Li

2017-01-01

Allergic inflammation is induced by allergens and leads to various allergic diseases, including rhinitis, asthma and conjunctivitis. Histamine is important in the pathogenesis of an immunoglobulin E-dependent allergic reaction and results in the secretion of cytokines associated with inflammation. Angelica dahurica (A. dahurica) is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. The present study investigated the chemical constituents from A. dahurica and evaluated their reductive effect on allergic inflammation. As a result, 15 compounds including 13 coumarins have been identified as isoimperatorin (1), imperatorin (2), oxypeucedanin (3), oxypeucedanin hydrate (4), bergapten (5), byakangelicin (6), phellopterin (7), byakangelicol (8), isopimpinellin (9), xanthotoxol (10), xanthotoxin (11), pimpinellin (12), scopoletin (13), β-sitosterol (14) and daucosterol (15). Compounds 1–13 were able to reduce the release of histamine, with compounds 4–6 exhibiting the most potent activity. Furthermore, compounds 1–12 were able to inhibit the secretion of tumor necrosis factor-α, interleukin (IL)-1β and IL-4, with compounds 5 and 7 exhibiting the strongest inhibitory effects. These compounds implemented the inhibitory effects on the expression of inflammatory cytokine genes through the inhibition of nuclear factor-κB activation. Virtual screening by a docking program indicated that compound 3 is a potent histamine H1 receptor antagonist. Additionally, the calculated physicochemical properties of these compounds support most furanocoumarins to be delivered to binding sites and permeate the cell membrane. The present findings contribute to understanding how A. dahurica attenuates allergic inflammation. PMID:28673013

Anti-Wrinkle and Anti-Inflammatory Effects of Active Garlic Components and the Inhibition of MMPs via NF-κB Signaling

PubMed Central

Kim, So Ra; Jung, Yu Ri; An, Hye Jin; Kim, Dae Hyun; Jang, Eun Ji; Choi, Yeon Ja; Moon, Kyoung Mi; Park, Min Hi; Park, Chan Hum; Chung, Ki Wung; Bae, Ha Ram; Choi, Yung Whan; Kim, Nam Deuk; Chung, Hae Young

2013-01-01

Skin aging is a multisystem degenerative process caused by several factors, such as, UV irradiation, stress, and smoke. Furthermore, wrinkle formation is a striking feature of photoaging and is associated with oxidative stress and inflammatory response. In the present study, we investigated whether caffeic acid, S-allyl cysteine, and uracil, which were isolated from garlic, modulate UVB-induced wrinkle formation and effect the expression of matrix-metalloproteinase (MMP) and NF-κB signaling. The results obtained showed that all three compounds significantly inhibited the degradation of type І procollagen and the expressions of MMPs in vivo and attenuated the histological collagen fiber disorder and oxidative stress in vivo. Furthermore, caffeic acid and S-allyl cysteine were found to decrease oxidative stress and inflammation by modulating the activities of NF-κB and AP-1, and uracil exhibited an indirect anti-oxidant effect by suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions levels and downregulating transcriptional factors. These results suggest that the anti-wrinkle effects of caffeic acid, S-allyl cysteine, and uracil are due to anti-oxidant and/or anti-inflammatory effects. Summarizing, caffeic acid, S-allyl cysteine, and uracil inhibited UVB-induced wrinkle formation by modulating MMP via NF-κB signaling. PMID:24066081

[In vitro anti-inflammatory and free radical scavenging activities of flavans from Ilex centrochinensis].

PubMed

Li, Lu-jun; Yu, Li-juan; Li, Yan-ci; Liu, Meng-yuan; Wu, Zheng-zhi

2015-04-01

This study was carried out to evaluate the anti-inflammatory and free radical scavenging activities of flavans from flex centrochinensis S. Y. Hu in vitro and their structure-activity relationship. LPS-stimulated RAW 264.7 macrophage was used as inflammatory model. MTT assay for cell availability, Griess reaction for nitric oxide (NO) production, the content of TNF-alpha, IL-1beta, IL-6 and PGE, were detected with ELISA kits; DPPH, superoxide anion and hydroxyl free radicals scavenging activities were also investigated. According to the result, all flavans tested exhibited anti-inflammatory effect in different levels. Among them, compounds 1, 3, 4 and 6 showed potent anti-inflammatory effect through the inhibition of NO, TNF-alpha, IL-lp and IL-6, of which 1 was the most effective inhibitor, however, 2 and 5 were relatively weak or inactive. The order of free radical scavenging activities was similar to that of anti-inflammatory activities. Therefore, these results suggest that 3, 4 and 6, especially of 1, were,in part responsible for the anti-inflammatory and free radical scavenging activity of Ilex centrochinensis. Hydroxyl group at 4'-position of B-ring plays an important role in the anti-inflammatory and free radical scavenging capacities.

Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity

PubMed Central

2012-01-01

Background As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time. Methods Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p < 0.05 (two-tailed). Results Results indicate that the curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK. Conclusions Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model. PMID:22909087

Inhibitory activity of Sargassum hemiphyllum sulfated polysaccharide in arachidonic acid-induced animal models of inflammation.

PubMed

Hwang, Pai-An; Hung, Yu-Lan; Chien, Shih-Yung

2015-03-01

Sargassum hemiphyllum is a common plant found on the coasts of Taiwan; it has been used as an anti-inflammatory agent in traditional herbal medicine. This study aimed to evaluate the anti-inflammatory effects of S. hemiphyllum sulfated polysaccharide (SHSP) using two different mouse models. In both arachidonic acid-induced ear inflammatory gavage and paint models, SHSP decreased ear swelling and erythema. In addition, SHSP decreased the production of myeloperoxidase, nitric oxide, interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in a dose-dependent manner. Histological examination results showed that SHSP reduced the area of neutrophilic infiltration in inflamed ears. The anti-inflammatory activity of SHSP has already been demonstrated in vitro. In this study, SHSP extracted from the same species of brown seaweed exhibited anti-inflammatory activity in both oral and topical applications in vivo. Therefore, SHSP may play a role in the treatment of inflammatory diseases. Copyright © 2014. Published by Elsevier B.V.

Morinda citrifolia lipid transfer protein 1 exhibits anti-inflammatory activity by modulation of pro- and anti-inflammatory cytokines.

PubMed

Campos, Dyély C O; Costa, Andrea S; Luz, Patrícia B; Soares, Pedro M G; Alencar, Nylane M N; Oliveira, Hermógenes D

2017-10-01

Previous reports have demonstrated that a thermostable lipid transfer protein isolated from noni seeds (McLTP 1 ; 9.4kDa) displays anti-nociceptive and anti-inflammatory activities. This work aimed to investigate the underlying mechanisms of the anti-inflammatory activity of McLTP 1 in mice. The protein was solubilised in sterile saline (0.9% NaCl) immediately before the treatment of mice by oral or intraperitoneal routes at doses of 8mg/kg. Given orally or intraperitoneally, McLTP 1 significantly inhibited (p<0.05) cell migration in experimental models of carrageenan-induced peritonitis and the formation of paw oedema induced by carrageenan and dextran. Additionally, McLTP 1 demonstrated the ability to significantly inhibit the production of the cytokines IL-1β, IL-6, and TNF-α (p<0.05) and to promote an increase in the production of the anti-inflammatory cytokine IL-10. The treatment of mice with McLTP 1 by the oral or i.p route reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury. This study suggested that the observed anti-inflammatory effects of McLTP 1 can be related to modulation of pro- and anti-inflammatory cytokine levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Potent Anti-Inflammatory Activity of Pyrenocine A Isolated from the Marine-Derived Fungus Penicillium paxilli Ma(G)K

PubMed Central

Toledo, Thaís Regina; Dejani, Naiara N.; Monnazzi, Luis Gustavo Silva; Kossuga, Miriam H.; Berlinck, Roberto G. S.; Sette, Lara D.; Medeiros, Alexandra I.

2014-01-01

Very little is known about the immunomodulatory potential of secondary metabolites isolated from marine microorganisms. In the present study, we characterized pyrenocine A, which is produced by the marine-derived fungus Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A was able to suppress, both pretreatment and posttreatment, the LPS-induced activation of macrophages via the inhibition of nitrite production and the synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti-inflammatory effects on the expression of receptors directly related to cell migration (Mac-1) as well as costimulatory molecules involved in lymphocyte activation (B7.1). Nitrite production was inhibited by pyrenocine A in macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A acts through the MyD88-dependent intracellular signaling pathway. Moreover, pyrenocine A is also able to inhibit the expression of genes related to NFκB-mediated signal transduction on macrophages stimulated by LPS. Our results indicate that pyrenocine A has promissory anti-inflammatory properties and additional experiments are necessary to confirm this finding in vivo model. PMID:24574582

The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo

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

Eisele, Petra Sabine; Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich; Furrer, Regula

The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1α allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1α and the related PGC-1β counteract the induction of inflammation by reducing the activity of the nuclear factor κB (NFκB). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC-1α/-1β transgenic mice in vivo in the basal state as well as after an acute inflammatory insult. Surprisingly, we observed amore » PGC-1-dependent alteration of the cytokine profile characterized by an increase in anti-inflammatory factors and a strong suppression of the pro-inflammatory interleukin 12 (IL-12). In conclusion, the anti-inflammatory environment in muscle that is promoted by the PGC-1s might contribute to the beneficial effects of these coactivators on muscle function and provides a molecular link underlying the tight mutual regulation of metabolism and inflammation. - Highlights: • Muscle PGC-1s are insufficient to prevent acute systemic inflammation. • The muscle PGC-1s however promote a local anti-inflammatory environment. • This anti-inflammatory environment could contribute to the therapeutic effect of the PGC-1s.« less

In vitro antioxidant and anti-inflammatory activities of Jaceosidin from Artemisia princeps Pampanini cv. Sajabal.

PubMed

Kim, Min-Jung; Han, Jong-Min; Jin, Yue-Yan; Baek, Nam-In; Bang, Myun-Ho; Chung, Hae-Gon; Choi, Myung-Sook; Lee, Kyung-Tae; Sok, Dai-Eun; Jeong, Tae-Sook

2008-04-01

Oxidized low-density lipoprotein (oxLDL) plays a key role in the inflammatory processes of atherosclerosis. Jaceosidin isolated from the methanolic extracts of the aerial parts of Artemisia princeps Pampanini cv. Sajabal was tested for antioxidant and anti-inflammatory activities. Jaceosidin inhibited the Cu(2+)-mediated LDL oxidation with IC(50) values of 10.2 microM in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. The antioxidant activities of jaceosidin were exhibited in the conjugated diene production, relative electrophoretic mobility, and apoB-100 fragmentation on copper-mediated LDL oxidation. Jaceosidin also inhibited the generation of reactive oxygen species (ROS) concerning in regulation of NF-kappaB signaling. And jaceosidin inhibited nuclear factor-kappa B (NF-kappaB) activity, nitric oxide (NO) production, and suppressed expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Evaluation of Caesalpinia pulcherrima Linn. for anti-inflammatory and antiulcer activities

PubMed Central

Sharma, Vivek; Rajani, G.P.

2011-01-01

Objective: To evaluate the ethanolic and aqueous extracts of aerial parts of Caesalpinia pulcherrima (Linn.) Sw. for anti-inflammatory and antiulcer activities. Materials and Methods: Anti-inflammatory action of the ethanolic and aqueous extracts of C. pulcherrima (100 and 200 mg/kg b.w.) (CPE and CPA) were evaluated by cotton pellet granuloma models. Pylorus ligation and aspirin induced ulcer models were employed for evaluating antiulcer activity for both the extracts. Ulcerogenic potential of CP was also evaluated. Result: The ethanolic and aqueous extracts of C. pulcherrima significantly decreased (P<0.01) the granuloma tissue development. CPE and CPA at both the doses exhibited significant (P<0.01) antiulcer activity by decreasing the ulcer score in both the ulcer models and it was not ulcerogenic. Conclusion: The ethanolic and aqueous extracts of aerial parts of C. pulcherrima (CPE and CPA) possess significant anti-inflammatory and antiulcer activities. PMID:21572651

Synthesis of some novel orcinol based coumarin triazole hybrids with capabilities to inhibit RANKL-induced osteoclastogenesis through NF-κB signaling pathway.

PubMed

Rama Krishna, Boddu; Thummuri, Dinesh; Naidu, V G M; Ramakrishna, Sistla; Venkata Mallavadhani, Uppuluri

2018-08-01

A total of twenty-two novel coumarin triazole hybrids (4a-4k and 6a-6k) were synthesized from orcinol in good to excellent yields of 70-94%. The structures of all the synthesized compounds were elucidated by spectroscopic techniques such as 1 H NMR, 13 C NMR, and HRMS. The anti-inflammatory potential of synthesized compounds was investigated against the proinflammatory cytokine, TNF-α on U937 cell line and compounds 4d, 4j, and 6j were found to exhibit promising anti-inflammatory activity. These three compounds were further screened against TNF-α on LPS-stimulated RAW 264.7 cells, which confirm their anti-inflammatory potential. Furthermore, the above said active compounds were tested for their inhibitory effect on RANKL-induced osteoclastogenesis in RAW 264.7 cells by using tartrate resistant acid phosphatase (TRAP) staining assay at 10 µM. Molecular mechanism studies demonstrated that compound 4d exhibited dose dependent inhibition of RANKL-induced osteoclastogenesis by suppression of the NF-kB pathway. Thus, compound 4d is a promising candidate for further optimization to develop as a potent anti-osteoporotic agent. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer's disease.

PubMed

García-Morales, Giovanni; Huerta-Reyes, Maira; González-Cortazar, Manasés; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Silva-García, Raúl; Román-Ramos, Rubén; Aguilar-Rojas, Arturo

2015-07-01

Bouvardia ternifolia has been used medicinally to treat inflammation. In the present study, we investigate the anti-Alzheimer's potential effect of the hydroalcoholic extract of B. ternifolia through evaluation of anti-inflammatory and antioxidant activities, quantification of the percentage inhibition of acetylcholinesterase activity, protection effect against β-amyloid fibrillar-induce neurotoxicity, and the identification of the main constituents. Our results show that B. ternifolia extract and ethyl acetate fraction induced anti-inflammatory effects by reducing inflammation by >70 %, while antioxidant test revealed significant IC50 values for flavonoid content fraction (30.67 ± 2.09 μg/ml) and ethyl acetate fraction (42.66 ± 0.93 μg/ml). The maximum inhibition of acetylcholinesterase was exhibited by scopoletin content fraction (38.43 ± 3.94 %), while ethyl acetate fraction exerted neuroprotective effect against β-amyloid peptide (83.97 ± 5.03 %). Phytochemical analysis, showed the presence of 3-O-quercetin glucopyranoside (415 mg/g), rutin (229.9 mg/g), ursolic and oleanolic acid (54 and 20.8 mg/g respectively), 3-O-quercetin rhamnopyranoside (12.8 mg/g), chlorogenic acid (9.5 mg/g), and scopoletin (1.38 mg/g). Our findings support the use of B. ternifolia since the extract induced significant neuroprotection against β-amyloid peptide, anti-inflammatory, antioxidant and anti-acetylcholinesterase effects that could be attributed to its contents of polyphenols, coumarins, and triterpenes, and encourage further studies for development of this extract as therapeutic agent in treatment of Alzheimer's disease.

Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases.

PubMed

Eng, Qian Yi; Thanikachalam, Punniyakoti Veeraveedu; Ramamurthy, Srinivasan

2018-01-10

The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported. This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research. Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017. EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated haemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant). EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity.

PubMed

Ezzat, Shahira M; Ezzat, Marwa I; Okba, Mona M; Menze, Esther T; Abdel-Naim, Ashraf B

2018-03-25

Ginger (Zingiber officinale Roscoe) is a well known anti-inflammatory drug in the Egyptian, Indian and Chinese folk medicines, yet its mechanism of action is unclear. To explore its mechanism of action and to correlate it to its biophytochemicals. Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated using protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated using carrageenan-induced rat paw edema in rats at doses 25, 50, 100 and 200mg/kg b.wt. All the tested extracts showed significant (p< 0.1) in vitro anti-inflammatory activities. The strongest anti-lipoxygenase activity was observed for AE that was more significant than that of diclofenac (58% and 52%, respectively) at the same concentration (125μg/ml). Purification of AE led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G1, G2 and G8 exhibited potent activity in all the studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw edema in a dose-dependent manner. AE (at 200mg/kg) showed significant reduction in production of PGE2, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES), myeloperoxidase (MPO) activity by 60%, 57%, 60%, 41%, 32% and 67%, respectively. AE at 100 and 200mg/kg was equipotent to indomethacin in reduction of NO x level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200mg/kg) prior to carrageenan. Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. This was evidenced by the dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenishment the total antioxidant capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual evaluation of some novel 2-amino-substituted coumarinylthiazoles as anti-inflammatory-antimicrobial agents and their docking studies with COX-1/COX-2 active sites.

PubMed

Chandak, Navneet; Kumar, Pawan; Kaushik, Pawan; Varshney, Parul; Sharma, Chetan; Kaushik, Dhirender; Jain, Sudha; Aneja, Kamal R; Sharma, Pawan K

2014-08-01

Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity.

Aurantiamide acetate from baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in Influenza A virus-infected cells.

PubMed

Zhou, Beixian; Yang, Zifeng; Feng, Qitong; Liang, Xiaoli; Li, Jing; Zanin, Mark; Jiang, Zhihong; Zhong, Nanshan

2017-03-06

Baphicacanthus cusia root also names "Nan Ban Lan Gen" has been traditionally used to prevent and treat influenza A virus infections. Here, we identified a peptide derivative, aurantiamide acetate (compound E17), as an active compound in extracts of B. cusia root. Although studies have shown that aurantiamide acetate possesses antioxidant and anti-inflammatory properties, the effects and mechanism by which it functions as an anti-viral or as an anti-inflammatory during influenza virus infection are poorly defined. Here we investigated the anti-viral activity and possible mechanism of compound E17 against influenza virus infection. The anti-viral activity of compound E17 against Influenza A virus (IAV) was determined using the cytopathic effect (CPE) inhibition assay. Viruses were titrated on Madin-Darby canine kidney (MDCK) cells by plaque assays. Ribonucleoprotein (RNP) luciferase reporter assay was further conducted to investigate the effect of compound E17 on the activity of the viral polymerase complex. HEK293T cells with a stably transfected NF-κB luciferase reporter plasmid were employed to examine the activity of compound E17 on NF-κB activation. Activation of the host signaling pathway induced by IAV infection in the absence or presence of compound E17 was assessed by western blotting. The effect of compound E17 on IAV-induced expression of pro-inflammatory cytokines was measured by real-time quantitative PCR and Luminex assays. Compound E17 exerted an inhibitory effect on IAV replication in MDCK cells but had no effect on avian IAV and influenza B virus. Treatment with compound E17 resulted in a reduction of RNP activity and virus titers. Compound E17 treatment inhibited the transcriptional activity of NF-κB in a NF-κB luciferase reporter stable HEK293 cell after stimulation with TNF-α. Furthermore, compound E17 blocked the activation of the NF-κB signaling pathway and decreased mRNA expression levels of pro-inflammatory genes in infected cells. Compound E17 also suppressed the production of IL-6, TNF-α, IL-8, IP-10 and RANTES from IAV-infected lung epithelial (A549) cells. These results indicate that compound E17 isolated from B. cusia root has potent anti-viral and anti-inflammatory effects on IAV-infected cells via inhibition of the NF-κB pathway. Therefore, compound E17 could be a potential therapeutic agent for the treatment of influenza. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activities.

PubMed

Nujić, Krunoslav; Smith, Marjorie; Lee, Michael; Belamarić, Daniela; Tomašković, Linda; Alihodžić, Sulejman; Malnar, Ivica; Polančec, Denis; Schneider, Klaus; Eraković Haber, Vesna

2012-02-29

In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti-inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. Copyright © 2011 Elsevier B.V. All rights reserved.

Oral delivery of Bifidobacterium longum expressing α-melanocyte-stimulating hormone to combat ulcerative colitis.

PubMed

Wei, Pijin; Yang, Yan; Ding, Qing; Li, Xiuying; Sun, Hanxiao; Liu, Zhaobing; Huang, Junli; Gong, Yahui

2016-02-01

α-Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide derived from pro-opiomelanocortin that exhibits potent anti-inflammatory properties by regulating the production of inflammatory mediators. This peptide has been well established in several inflammatory models, including inflammatory bowel disease (IBD). However, its extremely short duration in vivo limits its clinical application. To address this limitation, Bifidobacterium was used here as a carrier to deliver α-MSH. We utilized α-MSH-engineered Bifidobacterium against IBD, which is closely linked to immune and intestinal microbiota dysfunction. First, we constructed a Bifidobacterium longum secreting α-MSH (B. longum-α-MSH). We then tested the recombinant α-MSH expression and determined its bioactivity in HT-29 cells. To assess its effectiveness, B. longum-α-MSH was used against an ulcerative colitis (UC) model in rats induced by dextran sulfate sodium. The data showed that α-MSH expression in B. longum-α-MSH was effective, and its biological activity was similar to the synthesized one. This UC model experiment indicated that B. longum-α-MSH successfully colonized the intestinal gut, expressed bioactive α-MSH and had a significant anti-inflammatory effect. The results demonstrate the feasibility of preventing IBD by using B. longum-α-MSH.

A Phytopharmacological Review on a Medicinal Plant: Juniperus communis

PubMed Central

Bais, Souravh; Gill, Naresh Singh; Rana, Nitan; Shandil, Shandeep

2014-01-01

Juniperus communis is a shrub or small evergreen tree, native to Europe, South Asia, and North America, and belongs to family Cupressaceae. It has been widely used as herbal medicine from ancient time. Traditionally the plant is being potentially used as antidiarrhoeal, anti-inflammatory, astringent, and antiseptic and in the treatment of various abdominal disorders. The main chemical constituents, which were reported in J. communis L. are α-pinene, β-pinene, apigenin, sabinene, β-sitosterol, campesterol, limonene, cupressuflavone, and many others. This review includes the last 20 years journals and various books update on this plant, representing its pharmacological activity and health benefits against various diseases. PMID:27419205

A Phytopharmacological Review on a Medicinal Plant: Juniperus communis.

PubMed

Bais, Souravh; Gill, Naresh Singh; Rana, Nitan; Shandil, Shandeep

2014-01-01

Juniperus communis is a shrub or small evergreen tree, native to Europe, South Asia, and North America, and belongs to family Cupressaceae. It has been widely used as herbal medicine from ancient time. Traditionally the plant is being potentially used as antidiarrhoeal, anti-inflammatory, astringent, and antiseptic and in the treatment of various abdominal disorders. The main chemical constituents, which were reported in J. communis L. are α-pinene, β-pinene, apigenin, sabinene, β-sitosterol, campesterol, limonene, cupressuflavone, and many others. This review includes the last 20 years journals and various books update on this plant, representing its pharmacological activity and health benefits against various diseases.

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.

Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues.

PubMed

Lee, In-Seung; Cho, Dong-Hyuk; Kim, Ki-Suk; Kim, Kang-Hoon; Park, Jiyoung; Kim, Yumi; Jung, Ji Hoon; Kim, Kwanil; Jung, Hee-Jae; Jang, Hyeung-Jin

2018-02-01

Allergic asthma is the most common type in asthma, which is defined as a chronic inflammatory disease of the lung. In this study, we investigated whether embelin (Emb), the major component of Ardisia japonica BL. (AJB), exhibits anti-inflammatory effects on allergic asthma via inhibition of NF-κB activity using A549 cells and asthmatic airway epithelial tissues. Inflammation was induced in A549 cells, a human airway epithelial cell line, by IL-1β (10 ng/ml) treatment for 4 h. The effects of Emb on NF-κB activity and COX-2 protein expression in inflamed airway epithelial cells and human asthmatic airway epithelial tissues were analyzed via western blot. The secretion levels of NF-κB-mediated cytokines/chemokines, including IL-4, 6, 9, 13, TNF-α and eotaxin, were measured by a multiplex assay. Emb significantly blocked NF-κB activity in IL-1β-treated A549 cells and human asthmatic airway epithelial tissues. COX-2 expression was also reduced in both IL-1β-treated A549 cells and asthmatic tissues Emb application. Emb significantly reduced the secretion of IL-4, IL-6 and eotaxin in human asthmatic airway epithelial tissues by inhibiting activity of NF-κB. The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.

Anti-inflammatory, wound healing and in-vivo antioxidant properties of the leaves of Ficus amplissima Smith.

PubMed

Arunachalam, Karuppusamy; Parimelazhagan, Thangaraj

2013-01-09

Ficus amplissima, commonly known as kal-itchchi, being used in folklore medicine, leaves juice is applied externally on old chronic wounds and the latex is applied on the wound. There was no scientific evidence justifying the medicinal use of Ficus amplissima, therefore the present study was aimed at evaluation of anti-inflammatory, wound healing and in-vivo antioxidant activity of the plant. In the present study the acetone extract of Ficus amplissima leaves were studied for enzymatic antioxidant activity through different assays, anti-inflammatory by using carrageenan and histamine induced rat paw edema models (50mg, 100mg acetone extract) and wound healing activity by incorporating the two doses (1% (w/w) and 2% (w/w)) of acetone extract and simple ointment base B.P. in concentration of 0.5% (w/w) using excision and incision wound models in rats. In case of the excision wound model wound contraction and period of epithelization was studied while incision wound model was evaluated by determining tensile strength. Ficus amplissima leaves expressed the potent anti-inflammatory and in-vivo antioxidant activity where 100mg acetone extract showed high activity. Treatment of wound with ointment containing 2% (w/w) acetone extract exhibited significant (P<0.001) wound healing activity. The acetone extract of Ficus amplissima leaves exhibited better anti-inflammatory, wound healing and in-vivo antioxidant activity probably due to phenols constituents. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice via the NF-κB pathway.

PubMed

Chen, Haiming; Lu, Chuanjian; Liu, Huazhen; Wang, Maojie; Zhao, Hui; Yan, Yuhong; Han, Ling

2017-07-01

Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action. Effects of QC on PASI scores, back temperature, histopathological changes, oxidative/anti-oxidative indexes, pro-inflammatory cytokines and NF-κB pathway in IMQ-induced mice were investigated. Our results showed that QC could significantly reduce the PASI scores, decrease the temperature of the psoriasis-like lesions, and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC effectively attenuated levels of TNF-α, IL-6 and IL-17 in serum, increased activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin tissue induced by IMQ in mice. The mechanism may be associated with the down-regulation of NF-κB, IKKα, NIK and RelB expression and up-regulation of TRAF3, which were critically involved in the non-canonical NF-κB pathway. In conclusion, our present study demonstrated that QC had appreciable anti-psoriasis effects in IMQ-induced mice, and the underlying mechanism may involve the improvement of antioxidant and anti-inflammatory status and inhibition on the activation of the NF-κB signaling. Hence, QC, a naturally occurring flavone with potent anti-psoriatic effects, has the potential for further development as a candidate for psoriasis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibacterial and Anti-inflammatory Activities of Ppc-1, Active Principle of the Cellular Slime Mold Polysphondylium pseudo-candidum.

PubMed

Azelmat, Jabrane; Fiorito, Serena; Genovese, Salvatore; Epifano, Francesco; Grenier, Daniel

2015-01-01

The diisopentenyloxy quinolobactin derivative 3-methylbut-2-enyl-4-methoxy-8-[(3-methylbut-2-enyl)oxy] quinoline-2-carboxylate, also named as Ppc-1, has been initially isolated from the fruiting bodies of the cellular slime mold Polysphondylium pseudo-candidum. Given that few data are available in the literature concerning the biological properties of this compound, this study was undertaken to evaluate its antibacterial and anti-inflammatory properties. Ppc-1 exerted antibacterial activity on the Gram negative periodontopathogen Porphyromonas gingivalis, while it had no such effect on the other bacterial species tested. The antibacterial activity of Ppc-1 appeared to result from its ability to permeate the cell membrane. Using the U937-3xκB-LUC human monocytic cell line, Ppc-1 was found to dose-dependently inhibit the lipopolysaccharide-induced NF-κB activation, a signaling pathway that has been associated with inflammatory mediator secretion. In conclusion, Ppc-1, by exhibiting a dual mode of action including antibacterial and anti-inflammatory activities, may represent a promising targeted therapeutic agent for periodontal diseases.

Antibacterial, antioxidant, and topical anti-inflammatory activities of Bergia ammannioides: A wound-healing plant.

PubMed

Ezzat, Shahira M; Choucry, Mouchira A; Kandil, Zeinab A

2016-01-01

Despite the traditional use of Bergia ammannioides Henye ex Roth. (Elatinaceae) for the treatment of wounds in India, there is a scarcity of scientific data supporting this use. The objective of this study is to assess wound-healing potentiality of the plant, to study pharmacological activities that may contribute in eliminating wound complications, and to investigate the biologically active fractions. The ethanolic extract (EtOH) of the aerial parts was fractionated to obtain n-hexane (HxFr), chloroform (ClFr), ethyl acetate (EtFr), and n-butanol (BuOH) fractions. EtOH and its fractions were formulated in strength of 5 and 10% w/w ointment and tested for wound-healing activity using the excision model. The topical anti-inflammatory, in vitro antioxidant, and antibacterial activities were evaluated. HxFr and EtFr were chemically investigated to isolate their constituents. Application of EtOH, HxFr, and EtFr (10% w/w ointments) leads to 71.77, 85.62, and 81.29% healing of the wounds with an increase in the collagen content. HxFr had the strongest anti-inflammatory (64.5% potency relative to Voltaren®) and antibacterial activity (MIC = 104 μg/ml against Staphylococcus aureus), while EtFr showed the strongest antioxidant activity against DPPH, ABTS(•+), and super oxide radical with an IC50 value of 10.25 ± 0.01, 66.09 ± 0.76, and 167.33 ± 0.91 µg/ml, respectively. β-Sitosterol, lupeol, cyclolaudenol, and cycloartenol were isolated from HxFr. Quercetin, ellagic acid, kaempferol-3-O-α-l-rhamnoside, and quercetin-3-O-α-l-rhamnoside were isolated from EtFr. Our study presents scientific evidence for the efficacy of B. ammannioides in enhancing wound healing, and the first isolation of cyclolaudenol and cycloartenol from Bergia.

Sitosterol prevents obesity-related chronic inflammation.

PubMed

Kurano, Makoto; Hasegawa, Koji; Kunimi, Motoei; Hara, Masumi; Yatomi, Yutaka; Teramoto, Tamio; Tsukamoto, Kazuhisa

2018-02-01

The physiological roles of phytosterols in chronic inflammation, which are believed to be involved in the underlying mechanisms for metabolic diseases, have yet to be elucidated. Therefore, in the present study, we aimed to elucidate the physiological roles of phytosterols in both clinical studies and animal experiments. We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects (n=46) and non-diabetic subjects (n=178). Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels. When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet, we observed that the increase in body weight, the fatty liver changes, and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake. We also observed that the plasma IL-6 and TNF-α levels, the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6, TNF-α, and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice. These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Separation of flavonoids from Millettia griffithii with high-performance counter-current chromatography guided by anti-inflammatory activity.

PubMed

Tang, Huan; Wu, Bo; Chen, Kai; Pei, Heying; Wu, Wenshuang; Ma, Liang; Peng, Aihua; Ye, Haoyu; Chen, Lijuan

2015-02-01

Millettia griffithii is a unique Chinese plant located in the southern part of Yunnan Province. Up to now, there is no report about its phytochemical or related bioactivity research. In our previous study, the n-hexane crude extract of Millettia griffithii revealed significant anti-inflammatory activity at 100 μg/mL, inspiring us to explore the anti-inflammatory constituents. Four fractions (I, II, III, and A) were fractionated from n-hexane crude extract by high-performance counter-current chromatography with solvent system composed of n-hexane/ethyl acetate/methanol/water (8:9:8:9, v/v) and then were investigated for the potent anti-inflammatory activity. Fraction A, with the most potent inhibitory activity was further separated to give another four fractions (IV, V, VI, and B) with solvent system composed of n-hexane/ethyl acetate/methanol/water (8:4:8:4, v/v). Compound V and fraction B exhibited remarkable anti-inflammatory activity with nitric oxide inhibitory rate of 80 and 65%, which was worth further fractionation. Then, three fractions (VII, VIII, and IX) were separated from fraction B with a solvent system composed of n-hexane/ethyl acetate/methanol/water (8:1:8:1, v/v), with compound VIII demonstrating the most potent inhibitory activity (80%). Finally, the IC50 values of compound V and VIII were tested as 38.2 and 14.9 μM. The structures were identified by electrospray ionization mass spectrometry and(1)H and (13)C NMR spectroscopy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nickel(II) Complex of Polyhydroxybenzaldehyde N4-Thiosemicarbazone Exhibits Anti-Inflammatory Activity by Inhibiting NF-κB Transactivation

PubMed Central

Loh, Sheng Wei; Looi, Chung Yeng; Hassandarvish, Pouya; Phan, Alicia Yi Ling; Wong, Won Fen; Wang, Hao; Paterson, Ian C.; Ea, Chee Kwee; Mustafa, Mohd Rais; Maah, Mohd Jamil

2014-01-01

Background The biological properties of thiosemicarbazone have been widely reported. The incorporation of some transition metals such as Fe, Ni and Cu to thiosemicarbazone complexes is known to enhance its biological effects. In this study, we incorporated nickel(II) ions into thiosemicarbazone with N4-substitution groups H3L (H; H3L1, CH3; H3L2, C6H5; H3L3 and C2H5; H3L4) and examined its potential anti-inflammatory activity. Methodology/Principal Findings Four ligands (1–4) and their respective nickel-containing complexes (5–8) were synthesized and characterized. The compounds synthesized were tested for their effects on NF-κB nuclear translocation, pro-inflammatory cytokines secretion and NF-κB transactivation activity. The active compound was further evaluated on its ability to suppress carrageenan-induced acute inflammation in vivo. A potential binding target of the active compound was also predicted by molecular docking analysis. Conclusions/Significance Among all synthesized compounds tested, we found that complex [Ni(H2L1)(PPh3)]Cl (5) (complex 5), potently inhibited IκBα degradation and NF-κB p65 nuclear translocation in LPS-stimulated RAW264.7 cells as well as TNFα-stimulated HeLa S3 cells. In addition, complex 5 significantly down-regulated LPS- or TNFα-induced transcription of NF-κB target genes, including genes that encode the pro-inflammatory cytokines TNFα, IFNβ and IL6. Luciferase reporter assays confirmed that complex 5 inhibited the transactivation activity of NF-κB. Furthermore, the anti-inflammatory effect of complex 5 was also supported by its suppressive effect on carrageenan-induced paw edema formation in wild type C57BL/6 mice. Interestingly, molecular docking study showed that complex 5 potentially interact with the active site of IKKβ. Taken together, we suggest complex 5 as a novel NF-κB inhibitor with potent anti-inflammatory effects. PMID:24977407

Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin.

PubMed

Kim, Byung-Hak; Choi, Mi Sun; Lee, Hyun Gyu; Lee, Song-Hee; Noh, Kum Hee; Kwon, Sunho; Jeong, Ae Jin; Lee, Haeri; Yi, Eun Hee; Park, Jung Youl; Lee, Jintae; Joo, Eun Young; Ye, Sang-Kyu

2015-11-01

Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.

Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis.

PubMed

Xu, Danfeng; Lian, Di; Wu, Jing; Liu, Ying; Zhu, Mingjie; Sun, Jiaming; He, Dake; Li, Ling

2017-08-04

Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-derived neurotrophic factor (BDNF) has long been recommended for the treatment of CNS diseases due to its powerful neuro-survival properties, as well as its recently reported anti-inflammatory and anti-apoptotic effects in vitro and in vivo. In this study, we investigated the effects of BDNF-related signaling on the inflammatory response and hippocampal apoptosis in experimental models of pneumococcal meningitis. Pretreatment with exogenous BDNF or the tropomyosin-receptor kinase B (TrkB) inhibitor k252a was performed to assess the activation or inhibition of the BDNF/TrkB-signaling axis prior to intracisternal infection with live S. pneumoniae. At 24 h post-infection, rats were assessed for clinical severity and sacrificed to harvest the brains. Paraffin-embedded brain sections underwent hematoxylin and eosin staining to evaluate pathological severity, and cytokine and chemokine levels in the hippocampus and cortex were evaluated by enzyme-linked immunosorbent assay. Additionally, apoptotic neurons were detected in the hippocampal dentate gyrus by terminal deoxynucleotidyl transferase dUTP-nick-end labeling, key molecules associated with the related signaling pathway were analyzed by real-time polymerase chain reaction and western blot, and the DNA-binding activity of nuclear factor kappa B (NF-κB) was measured by electrophoretic mobility shift assay. Rats administered BDNF exhibited reduced clinical impairment, pathological severity, and hippocampal apoptosis. Furthermore, BDNF pretreatment suppressed the expression of inflammatory factors, including tumor necrosis factor α, interleukin (IL)-1β, and IL-6, and increased the expression of the anti-inflammatory factor IL-10. Moreover, BDNF pretreatment increased TrkB expression, activated downstream phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and inhibited the myeloid differentiation primary response gene 88 (MyD88)/NF-κB-signaling pathway. These data suggested that BDNF administration exerted anti-inflammatory and anti-apoptotic effects on an experimental pneumococcal meningitis model via modulation of MyD88/NF-κB- and PI3K/AKT-signaling pathways. Our results indicated that treatment with exogenous BDNF might constitute a potential therapeutic strategy for the treatment of bacterial meningitis.

Molecular targets and anti-cancer potential of escin.

PubMed

Cheong, Dorothy H J; Arfuso, Frank; Sethi, Gautam; Wang, Lingzhi; Hui, Kam Man; Kumar, Alan Prem; Tran, Thai

2018-05-28

Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More recently, escin is being actively investigated for its potential activity against diverse cancers. It exhibits anti-cancer effects in many cancer cell models including lung adenocarcinoma, hepatocellular carcinoma and leukemia. Escin also attenuates tumor growth and metastases in various in vivo models. Importantly, escin augments the effects of existing chemotherapeutic drugs, thereby supporting the role of escin as an adjunct or alternative anti-cancer therapy. The beneficial effects of escin can be attributed to its inhibition of proliferation and induction of cell cycle arrest. By regulating transcription factors/growth factors mediated oncogenic pathways, escin also potentially mitigates chronic inflammatory processes that are linked to cancer survival and resistance. This review provides a comprehensive overview of the current knowledge of escin and its potential as an anti-cancer therapy through its anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation.

PubMed

Zhou, Hong Yu; Shin, Eun Myoung; Guo, Lian Yu; Youn, Ui Joung; Bae, KiHwan; Kang, Sam Sik; Zou, Li Bo; Kim, Yeong Shik

2008-05-31

The extracts or constituents from the bark of Magnolia (M.) obovata are known to have many pharmacological activities. 4-Methoxyhonokiol, a neolignan compound isolated from the stem bark of M. obovata, was found to exhibit a potent anti-inflammatory effect in different experimental models. Pretreatment with 4-methoxyhonokiol (i.p.) dose-dependently inhibited the dye leakage and paw swelling in an acetic-acid-induced vascular permeability assay and a carrageenan-induced paw edema assay in mice, respectively. In the lipopolysaccharide (LPS)-induced systemic inflammation model, 4-methoxyhonokiol significantly inhibited plasma nitric oxide (NO) release in mice. To identify the mechanisms underlying this anti-inflammatory action, we investigated the effect of 4-methoxyhonokiol on LPS-induced responses in a murine macrophage cell line, RAW 264.7. The results demonstrated that 4-methoxyhonokiol significantly inhibited LPS-induced NO production as well as the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, 4-methoxyhonokiol inhibited LPS-mediated nuclear factor-kappaB (NF-kappaB) activation via the prevention of inhibitor kappaB (IkappaB) phosphorylation and degradation. 4-Methoxyhonokiol had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), whereas it attenuated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) in a concentration-dependent manner. Taken together, our data suggest that 4-methoxyhonokiol is an active anti-inflammatory constituent of the bark of M. obovata, and that its anti-inflammatory property might be a function of the inhibition of iNOS and COX-2 expression via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-kappaB activation in RAW 264.7 macrophages.

Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via Suppression of TAK1.

PubMed

Yang, Woo Seok; Yang, Eunju; Kim, Min-Jeong; Jeong, Deok; Yoon, Deok Hyo; Sung, Gi-Ho; Lee, Seungihm; Yoo, Byong Chul; Yeo, Seung-Gu; Cho, Jae Youl

2018-01-01

Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-[Formula: see text]B and AP-1.

Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of Pluchea indica Less. (Asteraceae).

PubMed

Gomes, A; Saha, Archita; Chatterjee, Ipshita; Chakravarty, A K

2007-09-01

We reported previously that the methanolic root extract of the Indian medicinal plant Pluchea indica Less. (Asteraceae) could neutralize viper venom-induced action [Alam, M.I., Auddy, B., Gomes, A., 1996. Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and P. indica) root extracts. Phytother. Res. 10, 58-61]. The present study reports the neutralization of viper and cobra venom by beta-sitosterol and stigmasterol isolated from the root extract of P. indica Less. (Asteraceae). The active fraction (containing the major compound beta-sitosterol and the minor compound stigmasterol) was isolated and purified by silica gel column chromatography and the structure was determined using spectroscopic analysis (EIMS, (1)H NMR, (13)C NMR). Anti-snake venom activity was studied in experimental animals. The active fraction was found to significantly neutralize viper venom-induced lethal, hemorrhagic, defibrinogenation, edema and PLA(2) activity. Cobra venom-induced lethality, cardiotoxicity, neurotoxicity, respiratory changes and PLA(2) activity were also antagonized by the active component. It potentiated commercial snake venom antiserum action against venom-induced lethality in male albino mice. The active fraction could antagonize venom-induced changes in lipid peroxidation and superoxide dismutase activity. This study suggests that beta-sitosterol and stigmasterol may play an important role, along with antiserum, in neutralizing snake venom-induced actions.

Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-α and IL-6 production in LPS-stimulated mouse peritoneal macrophages in vitro through MAPK pathway.

PubMed

Niu, Xiaofeng; Wang, Yu; Li, Weifeng; Zhang, Hailin; Wang, Xiumei; Mu, Qingli; He, Zehong; Yao, Huan

2015-12-01

Esculin, a coumarinic derivative found in Aesculus hippocastanum L. (Horse-chestnut), has been reported to have potent anti-inflammatory properties. The present study is designed to investigate the protective effects of esculin on various inflammation models in vivo and in vitro and to clarify the possible mechanism. Induced-animal models of inflammation and lipopolysaccharide (LPS)-challenged mouse peritoneal macrophages were used to examine the anti-inflammatory activity of esculin. In present study, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, and carrageenan-induced mouse pleurisy were attenuated by esculin. In vitro, the pro-inflammatory cytokine levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in supernatant were reduced by esculin. Meanwhile, we found that esculin significantly inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathway in peritoneal macrophages. These results suggest that esculin has potent anti-inflammatory activities in vivo and in vitro, which may involve the inhibition of the MAPK pathway. Esculin may be a promising preventive agent for inflammatory diseases in human. Copyright © 2015 Elsevier B.V. All rights reserved.

[Antioxidant and anti-inflammatory activities of Moroccan Erica arborea L].

PubMed

Amezouar, F; Badri, W; Hsaine, M; Bourhim, N; Fougrach, H

2013-12-01

The present study was carried out to evaluate the antioxidant and anti-inflammatory capacity, and acute toxicity of Moroccan Erica arborea leaves. Antioxidant capacity was assessed by diphenyle-picryl-hydrazyl (DPPH), phosphomolybdate (PPM) and ferric reducing antioxidant power (FRAP) tests and anti-inflammatory capacity was evaluated by hind paw oedema model using carrageenan-induced inflammation in rat. The acute toxicity was evaluated using mice. Acute toxicity of ethanolic extract of E. arborea showed no sign of toxicity at dose of 5 g/kg B.W. Our extracts have important antioxidant properties. The efficient concentration of the ethanolic extract (10.22 μg/ml) required for decreasing initial DPPH concentration by 50% was comparable to that of standard solution butyl-hydroxy-toluene (BHT) (8.87 μg/ml). The administration of ethanolic extract at doses of 200 and 400mg/kg B.W. was able to prevent plantar oedema and exhibited a significant inhibition against carrageenan-induced inflammation when compared to the control group (NaCl 0.9%) but comparable to those of diclofenac (reference drug). Our results show that the leaves of E. arborea may contain some bioactive compounds which are responsible for the antioxidant and anti-inflammatory activities observed here. Our finding may indicate the possibility of using the extracts of this plant to prevent the antioxidant and inflammatory processes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Antioxidant and Anti-Inflammatory Effects of Selected Natural Compounds Contained in a Dietary Supplement on Two Human Immortalized Keratinocyte Lines

PubMed Central

Serini, Simona; Mondella, Nadia; Celleno, Leonardo; Lanza, Paola; Calviello, Gabriella

2014-01-01

Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, α-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro. Each component was administered, alone or in combination, to human keratinocytes, and the inhibition of Reactive Oxygen Species production and lipid peroxidation as well as the ability to reduce inflammatory cytokine secretion and to modulate Nuclear Factor-κB pathway was evaluated. The combination exhibited high antioxidant activity and in specific conditions the combination's efficiency was higher than that of the most powerful components administered individually. Moreover, the combination showed remarkable anti-inflammatory properties. It reduced more efficiently than each component the secretion of Monocyte Chemoattractant Protein-1, a crucial cytokine for the development of chronic inflammation in skin, and inhibited Nuclear Factor-κB molecular pathway. Overall, our findings suggest that the combined formulation may have the potential to powerfully inhibit oxidative stress and inflammation at skin level. PMID:25197638

Inhibitory effects of black pepper (Piper nigrum) extracts and compounds on human tumor cell proliferation, cyclooxygenase enzymes, lipid peroxidation and nuclear transcription factor-kappa-B.

PubMed

Liu, Yunbao; Yadev, Vivek R; Aggarwal, Bharat B; Nair, Muraleedharan G

2010-08-01

Black pepper (Piper nigrum) and hot pepper (Capsicum spp.) are widely used in traditional medicines. Although hot Capsicum spp. extracts and its active principles, capsaicinoids, have been linked with anticancer and anti-inflammatory activities, whether black pepper and its active principle exhibit similar activities is not known. In this study, we have evaluated the antioxidant, anti-inflammatory and anticancer activities of extracts and compounds from black pepper by using proinflammatory transcription factor NF-kappaB, COX-1 and -2 enzymes, human tumor cell proliferation and lipid peroxidation (LPO). The capsaicinoids, the alkylamides, isolated from the hot pepper Scotch Bonnet were also used to compare the bioactivities of alkylamides and piperine from black pepper. All compounds derived from black pepper suppressed TNF-induced NF-kappaB activation, but alkyl amides, compound 4 from black pepper and 5 from hot pepper, were most effective. The human cancer cell proliferation inhibitory activities of piperine and alklyl amides in Capsicum and black pepper were dose dependant. The inhibitory concentrations 50% (IC50) of the alklylamides were in the range 13-200 microg/mL. The extracts of black pepper at 200 microg/mL and its compounds at 25 microg/mL inhibited LPO by 45-85%, COX enzymes by 31-80% and cancer cells proliferation by 3.5-86.8%. Overall, these results suggest that black pepper and its constituents like hot pepper, exhibit anti-inflammatory, antioxidant and anticancer activities.

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.

In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent.

PubMed

Katanić, Jelena; Boroja, Tatjana; Mihailović, Vladimir; Nikles, Stefanie; Pan, San-Po; Rosić, Gvozden; Selaković, Dragica; Joksimović, Jovana; Mitrović, Slobodanka; Bauer, Rudolf

2016-12-04

Meadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions. The characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis. FUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50μg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25μg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05). The observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Molecular inflammation as an underlying mechanism of the aging process and age-related diseases.

PubMed

Chung, H Y; Lee, E K; Choi, Y J; Kim, J M; Kim, D H; Zou, Y; Kim, C H; Lee, J; Kim, H S; Kim, N D; Jung, J H; Yu, B P

2011-07-01

Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

Caffeic acid phenethyl ester suppresses monocyte adhesion to the endothelium by inhibiting NF-κB/NOX2-derived ROS signaling

PubMed Central

Nakahara, Risa; Makino, Junya; Kamiya, Tetsuro; Hara, Hirokazu; Adachi, Tetsuo

2016-01-01

Caffeic acid phenethyl ester (CAPE), one of the major polyphenols, exhibits anti-oxidative, anti-bacterial, and anti-cancer properties. Atherosclerosis is a chronic inflammatory disease, the progression of which is closely related to the accumulated adhesion of inflammatory monocytes/macrophages to the endothelium. We herein determined whether CAPE and its derivatives suppressed THP-1 cell adhesion to human umbilical vein endothelial cells (HUVEC). Of the four polyphenols tested, CAPE significantly suppressed the 12-O-tetradecanoylphorbol 13-acetate (TPA)-elicited expression of cluster for differentiation (CD) 11b, 14, and 36, and this was accompanied by the inhibition of THP-1 cell adhesion to HUVEC. CAPE also suppressed the activation of TPA-elicited nuclear factor-κB (NF-κB) and accumulation of NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS), but did not affect extracellular signal-regulated kinase (ERK) phosphorylation. Taken together, these results demonstrated that CAPE suppressed THP-1 cell adhesion to HUVEC through, at least in part, the NF-κB, NOX2, and ROS-derived signaling axis. PMID:27257341

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression.

PubMed

Chen, Huajiao; Shi, Daohua; Niu, Peiguang; Zhu, Yanting; Zhou, Jintuo

2018-05-17

Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF- α , and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition. Georg Thieme Verlag KG Stuttgart · New York.

Anti-inflammatory effect of garlic 14-kDa protein on LPS-stimulated-J774A.1 macrophages.

PubMed

Rabe, Shahrzad Zamani Taghizadeh; Ghazanfari, Tooba; Siadat, Zahra; Rastin, Maryam; Rabe, Shahin Zamani Taghizadeh; Mahmoudi, Mahmoud

2015-04-01

Garlic 14-kDa protein is purified from garlic (Allium sativum L.) which is used in traditional medicine and exerts various immunomodulatory activities. The present study investigated the suppressive effect of garlic 14-kDa protein on LPS-induced expression of pro-inflammatory mediators and underlying mechanism in inflammatory macrophages. J774A.1 macrophages were treated with 14-kDa protein (5-30 μg/ml) with/without LPS (1 μg/ml) and the production of inflammatory mediators such as prostaglandin E2 (PGE2), TNF-α, and IL-1β released were measured using ELISA. Nitric oxide (NO) production was determined using the Griess method. The anti-inflammatory activity of 14-kDa protein was examined by measuring inducible nitric oxide synthase and cyclooxygenase-2 proteins using western blot. The expression of nuclear NF-κB p65 subunit was assessed by western blot. Garlic 14-kDa protein significantly inhibited the excessive production of NO, PGE, TNF-α, and IL-1β in lipopolysaccharide (LPS)-activated J774A.1 macrophages in a concentration-related manner without cytotoxic effect. Western blot analysis demonstrated that garlic 14-kDa protein suppressed corresponding inducible NO synthase expression and activated cyclooxygenase-2 protein expression. The inhibitory effect was mediated partly by a reduction in the activity and expression of transcription factor NF-κB protein. Our results suggested, for the first time, garlic 14-kDa protein exhibits anti-inflammatory properties in macrophages possibly by suppressing the inflammatory mediators via the inhibition of transcription factor NF-κB signaling pathway. The traditional use of garlic as anti-inflammatory remedy could be ascribed partly to 14-kDa protein content. This protein might be a useful candidate for controlling inflammatory diseases and further investigations in vivo.

Antibacterial and anti-inflammatory activity of a temporin B peptide analogue on an in vitro model of cystic fibrosis.

PubMed

Bezzerri, Valentino; Avitabile, Concetta; Dechecchi, Maria Cristina; Lampronti, Ilaria; Borgatti, Monica; Montagner, Giulia; Cabrini, Giulio; Gambari, Roberto; Romanelli, Alessandra

2014-10-01

Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive because their activity can easily be tuned after small modification to their primary sequence. Structure-activity studies previously reported by us allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram-positive and Gram-negative bacteria. In this paper, we investigated the antimicrobial and anti-inflammatory activity of the peptide TB_KKG6A against Pseudomonas aeruginosa. Interestingly, we found that the peptide exhibits antimicrobial activity at low concentrations, being able to downregulate the pro-inflammatory chemokines and cytokines interleukin (IL)-8, IL-1β, IL-6 and tumor necrosis factor-α produced downstream infected human bronchial epithelial cells. Experiments were carried out also with temporin B, which was found to show pro-inflammatory activity. Details on the interaction between TB_KKG6A and the P. aeruginosa LPS were obtained by circular dichroism and fluorescence studies. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Anti-inflammatory, antimycobacterial and genotoxic evaluation of Doliocarpus dentatus.

PubMed

Ishikawa, Raissa Borges; Leitão, Maicon Matos; Kassuya, Roberto Mikio; Macorini, Luis Fernando; Moreira, Flora Martinez Figueira; Cardoso, Claudia Andrea Lima; Coelho, Roberta Gomes; Pott, Arnildo; Gelfuso, Guilherme Martins; Croda, Julio; Oliveira, Rodrigo Juliano; Kassuya, Candida Aparecida Leite

2017-05-23

Doliocarpus dentatus is a medicinal plant widely used in Mato Grosso do Sul State for removing the swelling pain caused by the inflammation process and for treating urine retention. The genotoxic aspects and the anti-inflammatory and antimycobacterial activity of the ethanolic extract obtained from the leaves of D. dentatus (EEDd) were investigated. The EEDd was evaluated against Mycobacterium tuberculosis, and the compound composition was evaluated and identified by nuclear magnetic resonance (NMR). The mice received oral administration of EEDd (30-300mg/kg) in carrageenan models of inflammation, and EEDd (10-1000mg/kg) was assayed by the comet, micronucleus, and phagocytosis tests and by the peripheral leukocyte count. Phenols (204.04mg/g), flavonoids (89.17mg/g), and tannins (12.05mg/g) as well as sitosterol-3-O-β-D-glucopyranoside, kaempferol 3-O-α-L-rhamnopyranoside, betulinic acid and betulin were present in the EEDd. The value of minimal inhibitory concentration (MIC) of EEDd was 62.5µg/mL. The EEDd induced a significant decrease in the edema, mechanical hypersensitivity and leukocyte migration induced by carrageenan. The comet and micronucleus tests indicated that the EEDd was not genotoxic. The EEDd also did not change the phagocytic activity or the leukocyte perLipheral count. The EEDd does not display genotoxicity, phagocytosis and could act as an antimycobacterial and anti-inflammatory agent. This study should contribute to ensuring the safe use of EEDd. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities.

PubMed

Mathema, Vivek Bhakta; Koh, Young-Sang; Thakuri, Balkrishna Chand; Sillanpää, Mika

2012-04-01

Parthenolide, a naturally occurring sesquiterpene lactone derived from feverfew (Tanacetum parthenium), exhibits exceptional anti-cancer and anti-inflammatory properties, making it a prominent candidate for further studies and drug development. In this review, we briefly investigate molecular events and cell-specific activities of this chemical in relation to cytochrome c, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), signal transduction and activation of transcription (STAT), reactive oxygen species (ROS), TCP, HDACs, microtubules, and inflammasomes. This paper reports that parthenolide shows strong NF-κB- and STAT-inhibition-mediated transcriptional suppression of pro-apoptotic genes. This compound acts both at the transcriptional level and by direct inhibition of associated kinases (IKK-β). Similarly, this review discusses parthenolide-induced ROS-mediated apoptosis of tumor cells via the intrinsic apoptotic signaling pathway. The unique ability of this compound to not harm normal cells but at the same time induce sensitization to extrinsic as well as intrinsic apoptosis signaling in cancer cells provides an important, novel therapeutic strategy for treatment of cancer and inflammation-related disorders.

The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo.

PubMed

Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

2012-03-23

A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Chalcone Derivatives: Anti-inflammatory Potential and Molecular Targets Perspectives.

PubMed

Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

2017-11-20

Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold has gained considerable scientific interest in medicinal chemistry owing to its simple chemistry, ease in synthesizing a variety of derivatives and exhibiting a broad range of promising pharmacological activities by modulating several molecular targets. A number of natural and (semi-) synthetic chalcone derivatives have demonstrated admirable anti-inflammatory activity due to their inhibitory potential against various therapeutic targets like Cyclooxygenase (COX), Lipooxygenase (LOX), Interleukins (IL), Prostaglandins (PGs), Nitric Oxide Synthase (NOS), Leukotriene D4 (LTD4), Nuclear Factor-κB (NF- κB), Intracellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Monocyte Chemoattractant Protein-1 (MCP-1) and TLR4/MD-2, etc. The chalcone scaffold with hydroxyl, methoxyl, carboxyl, prenyl group and/or heterocyclic ring substitution like thiophene/furan/indole showed promising anti-inflammatory activity. In this review, a comprehensive study (from the year 1991 to 2016) on multi-targets of inflammatory interest, related inflammation reactions and their treatment by chalcone-based inhibitors acting on various molecular targets entailed in inflammation, Structure-Activity Relationships (SARs), Mechanism of Actions (MOAs), and patents are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cleome rutidosperma and Euphorbia thymifolia Suppress Inflammatory Response via Upregulation of Phase II Enzymes and Modulation of NF-κB and JNK Activation in LPS-Stimulated BV2 Microglia

PubMed Central

Ding, Hsiou-Yu; Wu, Pei-Shan; Wu, Ming-Jiuan

2016-01-01

Cleome rutidosperma DC. and Euphorbia thymifolia L. are herbal medicines used in traditional Indian and Chinese medicine to treat various illnesses. Reports document that they have antioxidant and anti-inflammatory activities; nonetheless, the molecular mechanisms involved in their anti-inflammatory actions have not yet been elucidated. The anti-neuroinflammatory activities and underlying mechanisms of ethanol extracts of Cleome rutidosperma (CR) and Euphorbia thymifolia (ET) were studied using lipopolysaccharide (LPS)-stimulated microglial cell line BV2. The morphology changes and production of pro-inflammatory mediators were assayed. Gene expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, and CC chemokine ligand (CCL)-2, as well as phase II enzymes such as heme oxygenase (HO)-1, the modifier subunit of glutamate cysteine ligase (GCLM) and NAD(P)H quinone dehydrogenase 1 (NQO1), were further investigated using reverse transcription quantitative-PCR (RT-Q-PCR) and Western blotting. The effects of CR and ET on mitogen activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling pathways were examined using Western blotting and specific inhibitors. CR and ET suppressed BV2 activation, down-regulated iNOS and COX-2 expression and inhibited nitric oxide (NO) overproduction without affecting cell viability. They reduced LPS-mediated tumor necrosis factor (TNF) and IL-6 production, attenuated IL-1β and CCL2 expression, but upregulated HO-1, GCLM and NQO1 expression. They also inhibited p65 NF-κB phosphorylation and modulated Jun-N terminal kinase (JNK) activation in BV2 cells. SP600125, the JNK inhibitor, significantly augmented the anti-IL-6 activity of ET. NF-κB inhibitor, Bay 11-7082, enhanced the anti-IL-6 effects of both CR and ET. Znpp, a competitive inhibitor of HO-1, attenuated the anti-NO effects of CR and ET. Our results show that CR and ET exhibit anti-neuroinflammatory activities by inhibiting pro-inflammatory mediator expression and production, upregulating HO-1, GCLM and NQO1, blocking NF-κB and modulating JNK signaling pathways. They may offer therapeutic potential for suppressing overactivated microglia and alleviating neurodegeneration. PMID:27618898

Anti-inflammatory effect of Naravelia zeylanica DC via suppression of inflammatory mediators in carrageenan-induced abdominal oedema in zebrafish model.

PubMed

Ekambaram, Sanmuga Priya; Perumal, Senthamil Selvan; Pavadai, Selvaranjani

2017-02-01

The traditional herbal medicines are receiving great importance in the health care sector, especially in Indian system of medicine, i.e, Ayurveda. The present study focused on the standardization of Naravelia zeylanica (L.) DC in terms of its active phytochemicals and to evaluate the anti-inflammatory activity of ethanol extract of N. zeylanica (ENZ). An analytical method was developed by high-performance liquid chromatography for simultaneous determination of β-sitosterol, lupeol and oleanolic acid in ENZ. The cell viability of ENZ was investigated using MTT assay. IC 50 value of ENZ on cell viability was found to be 653.01 µg/mL. To determine the anti-inflammatory activity of ENZ by in vitro method, LPS was added to the macrophage cells to induce activation and ENZ was further added to observe the recovery of inflamed cells. These cells when treated with ENZ, the percentage of viable cells were considerably increased to 74.68%. Loss of mitochondrial membrane potential on treatment with LPS and its recovery by ENZ was studied and found that the number of cells that were damaged on treatment with ENZ + LPS was comparatively lesser than treatment with LPS only. An in vivo anti-inflammatory study was carried out in carrageenan-induced abdominal oedema method in adult zebrafish which revealed the percentage inhibition of inflammation at graded dose levels of ENZ as 23.5% at 100 mg/kg, 62.4% at 200 mg/kg and 87.05% at 350 mg/kg when compared with standard of diclofenac which showed 85% inhibition at 100 mg/kg. The PCR amplification of DNA extracted from adult zebrafish showed that increased concentration of ENZ considerably downregulates the expression of TNF-α and iNOS, the mediators of inflammation.

Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers.

PubMed

Ukiya, Motohiko; Akihisa, Toshihiro; Yasukawa, Ken; Tokuda, Harukuni; Suzuki, Takashi; Kimura, Yumiko

2006-12-01

Ten oleanane-type triterpene glycosides, 1-10, including four new compounds, calendulaglycoside A 6'-O-methyl ester (2), calendulaglycoside A 6'-O-n-butyl ester (3), calendulaglycoside B 6'-O-n-butyl ester (5), and calendulaglycoside C 6'-O-n-butyl ester (8), along with five known flavonol glycosides, 11-15, were isolated from the flowers of marigold (Calendula officinalis). Upon evaluation of compounds 1-9 for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds, except for 1, exhibited marked anti-inflammatory activity, with ID50 values of 0.05-0.20 mg per ear. In addition, when 1-15 were evaluated against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA, compounds 1-10 exhibited moderate inhibitory effects (IC50 values of 471-487 mol ratio/32 pmol TPA). Furthermore, upon evaluation of the cytotoxic activity against human cancer cell lines in vitro in the NCI Developmental Therapeutics Program, two triterpene glycosides, 9 and 10, exhibited their most potent cytotoxic effects against colon cancer, leukemia, and melanoma cells.

Anti-inflammatory activity effect of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on TPA-induced skin inflammation in mice.

PubMed

Xu, Xue-Tao; Mou, Xue-Qing; Xi, Qin-Mei; Liu, Wei-Ting; Liu, Wen-Feng; Sheng, Zhao-Jun; Zheng, Xi; Zhang, Kun; Du, Zhi-Yun; Zhao, Su-Qing; Wang, Shao-Hua

2016-11-01

2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole, a key structural moiety exiting in many bioactive molecules, has been shown to have excellent selective activity on COX-2. In the present study, the anti-inflammatory activity and the underlying molecular mechanism of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on skin inflammation were assessed by 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Most of the compounds showed anti-inflammatory activity on TPA-induced skin inflammation. The anti-inflammatory activity of compound 4 showed higher anti-inflammatory activity than celecoxib (3.2-fold). Compound 4 pretreatment resulted in markedly suppression of TPA-induced IL-1β, IL-6, TNF-α, and COX-2, respectively. Furthermore, the mechanical study indicated that the anti-inflammatory activity of compound 4 was associated with its ability to inhibit activation of factor kappa-κB (NF-κB) by blocking IκB kinase (IKK) activities. Accordingly, compound 4 could be used as a potential anti-inflammatory agent for skin inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway

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

Wang, Yiting; Tu, Qunfei; Yan, Wei

Highlights: • CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-induced HepG2 cells. • CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells. • CXC195 regulated TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway in LPS-induced HepG2 cells. - Abstract: CXC195 showed strong protective effects in neuronal apoptosis by exerting its antioxidant activity. However, the anti-cancer effects of CXC195 is still with limited acquaintance. Here, we investigated the role of CXC195 in lipopolysaccharide (LPS)-induced human hepatocellular carcinoma (HCC) cells lines (HepG2) and the possible signaling pathways. CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-inducedmore » HepG2 cells. In addition, CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells, including TNF-α, iNOS, IL-1β, IL-6, CC chemokine ligand (CCL)-2, CCL-22 and epidermal growth factor receptor (EGFR). Moreover, CXC195 inhibited the expressions and interactions of TLR4, MyD88 and TAK1, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of ERK1/2, p38 and JNK. Our results suggested that treatment with CXC195 could attenuate the TLR4-mediated proliferation and inflammatory response in LPS-induced HepG2 cells, thus might be beneficial for the treatment of HCC.« less

Anti-inflammatory effect of thalidomide alone or in combination with augmentin in Klebsiella pneumoniae B5055 induced acute lung infection in BALB/c mice.

PubMed

Kumar, Vijay; Chhibber, Sanjay

2008-09-11

Thalidomide (alpha-naphtylimidoglutarimide), a psychoactive drug that readily crosses blood-brain barrier, has been shown to exhibit anti-inflammatory, anti-angiogenic, immunomodulatory properties through a mechanism that is not fully established. Keeping these properties in mind, we tried to find out the anti-inflammatory properties of thalidomide in mouse model of acute inflammation by introducing K. pneumoniae B5055 in BALB/c mice via intranasal route. The intranasal instillation of bacteria in this mouse model of acute pneumonia induced inflammation accompanied with significant increase in neutrophil infiltration in the lungs and also increased production of mediators of inflammation (i.e. malondialdehyde, myeloperoxidase and nitric oxide) in the lung tissue. The animals, which received thalidomide alone orally or in combination with augmentin, 30 min prior to bacterial instillation into the lungs via intranasal route, showed significant (P<0.05) decrease in neutrophil influx into the lungs and there was significant (P<0.05) decrease in the production of malondialdehyde, nitric oxide and myeloperoxidase activity. But the augmentin treatment alone did not decrease the malondialdehyde, myeloperoxidase and nitric oxide significantly (P>0.05) as compared to the control group. We therefore conclude that thalidomide ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P<0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, it can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in case of acute lung infection.

Agaricus blazei extract abrogates rotenone-induced dopamine depletion and motor deficits by its anti-oxidative and anti-inflammatory properties in Parkinsonic mice.

PubMed

Venkatesh Gobi, Veerappan; Rajasankar, Srinivasagam; Ramkumar, Muthu; Dhanalakshmi, Chinnasamy; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Chidambaram, Ranganathan; Kalandar, Ameer

2017-06-19

Neuroinflammation and oxidative damage are the two main malfactors that play an important role in the pathogenesis of experimental and clinical Parkinson's disease (PD). The current study was aimed to study the possible anti-oxidant and anti-inflammatory effects of the methanolic extract of Agaricus blazei (A. blazei) against rotenone-induced PD in mice. Male Albino mice were randomized and divided into the following groups: control, treated with rotenone (1 mg/kg/day), co-treated with rotenone and A. blazei (50, 100, and 200 mg/kg b.w.), and treated with A. blazei alone (200 mg/kg b.w.). After the end of the experimental period, behavioral studies, biochemical estimations, and protein expression patterns of inflammatory markers were studied. Rotenone treatment exhibited enhanced motor impairments, neurochemical deficits, oxidative stress, and inflammation, whereas oral administration of A. blazei extract attenuated the above-said indices. Even though further research is needed to prove its efficacy in clinical studies, the results of our study concluded that A. blazei extract offers a promising and new therapeutic lead for treatment of PD.

Design and synthesis of some new pyrazolyl-pyrazolines as potential anti-inflammatory, analgesic and antibacterial agents.

PubMed

Viveka, Shivapura; Dinesha; Shama, Prasanna; Nagaraja, Gundibasappa Karikannar; Ballav, Shuvankar; Kerkar, Savita

2015-08-28

In the present study, an efficient synthesis of some new substituted pyrazoline derivatives linked to a substituted pyrazole scaffold was performed by a multistep reaction sequences and compounds were screened for their anti-inflammatory, analgesic and antibacterial activities. The preliminary results revealed that the N-acylated (5e, 5h) and nitro substituted N-phenyl (6f) pyrazolyl-pyrazolines derivatives exhibited a very promising anti-inflammatory activity whereas 5h, 6f were interesting analgesic agents. The compounds with halo substituted phenyl group at C-3 of the pyrazoline ring (4a, 5g, 5h, 6a and 6b) were found to be active against clinical bacterial pathogens with MIC in the range of 0.2-0.4 mg/mL. Compound containing N-propionyl pyrazolyl-pyrazoline (5h) could be identified as the most active member within this study with a dual anti-inflammatory and antibacterial profile. Taken together, this study has led to the development of promising compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-κB and JNK MAPK signaling in microglial BV2 cells.

PubMed

Cai, Bangrong; Seong, Kyung-Joo; Bae, Sun-Woong; Chun, Changju; Kim, Won-Jae; Jung, Ji-Yeon

2018-06-08

Diosgenin, a precursor of steroid hormones in plants, is known to exhibit diverse pharmacological activities including anti-inflammatory properties. In this study, (3β, 25R)‑spirost‑5‑en‑3‑oxyl (2‑((2((2‑aminoethyl)amino)ethyl)amino)ethyl) carbamate (DGP), a new synthetic diosgenin derivative incorporating primary amine was used to investigate its anti-inflammatory effects and underlying mechanisms of action in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Pretreatment with DGP resulted in significant inhibition of nitric oxide (NO) synthesis, and down-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated microglial BV2 cells. In addition, DGP decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α). The inhibitory effects of DGP on these inflammatory mediators in LPS-stimulated microglial BV2 cells were regulated by NF-κB signaling through blocking p65 nuclear translocation and NF-κB p65/DNA binding activity. DGP also blocked the phosphorylation of c-Jun amino-terminal kinase (JNK), but not p38 kinase or extracellular signal-regulated kinases (ERK). The NF-κB inhibitor JSH-23 and JNK-specific inhibitor SP600125 significantly decreased NO production and IL-6 release in LPS-stimulated BV2 cells, respectively. The overall results demonstrate that DGP has anti-inflammatory effects on LPS-stimulated BV2 cells via inhibition of NF-κB and JNK activation, suggesting that DGP is a potential prophylactic agent in various neurodegenerative disorders. Copyright © 2018. Published by Elsevier B.V.

Chemical Characterization and Antioxidant, Antimicrobial, and Anti-Inflammatory Activities of South Brazilian Organic Propolis.

PubMed

Tiveron, Ana Paula; Rosalen, Pedro Luiz; Franchin, Marcelo; Lacerda, Risia Cristina Coelho; Bueno-Silva, Bruno; Benso, Bruna; Denny, Carina; Ikegaki, Masaharu; Alencar, Severino Matias de

2016-01-01

South Brazilian organic propolis (OP), which has never been studied before, was assessed and its chemical composition, scavenging potential of reactive oxygen species, antimicrobial and anti-inflammatory activities are herein presented. Based on the chemical profile obtained using HPLC, OP was grouped into seven variants (OP1-OP7) and all of them exhibited high scavenging activity, mainly against superoxide and hypochlorous acid species. OP1, OP2, and OP3 had the smallest minimal inhibitory concentration (MIC) against Gram-positive bacteria Streptococcus mutans, Streptococcus oralis, and Streptococcus aureus (12.5-100 μg/mL). OP1, OP2, OP3, and OP4 were more effective against Pseudomonas aeruginosa (Gram-negative), with MIC values ranging from 100 to 200 μg/mL. OP6 showed anti-inflammatory activity by decreasing NF-kB activation and TNF-α release in RAW 264.7 macrophages, and expressing the NF-κB-luciferase reporter stable gene. Therefore, south Brazilian OP can be considered an excellent source of bioactive compounds with great potential of application in the pharmaceutical and food industry.

Chemical Characterization and Antioxidant, Antimicrobial, and Anti-Inflammatory Activities of South Brazilian Organic Propolis

PubMed Central

Tiveron, Ana Paula; Rosalen, Pedro Luiz; Franchin, Marcelo; Lacerda, Risia Cristina Coelho; Bueno-Silva, Bruno; Benso, Bruna; Denny, Carina; Ikegaki, Masaharu; de Alencar, Severino Matias

2016-01-01

South Brazilian organic propolis (OP), which has never been studied before, was assessed and its chemical composition, scavenging potential of reactive oxygen species, antimicrobial and anti-inflammatory activities are herein presented. Based on the chemical profile obtained using HPLC, OP was grouped into seven variants (OP1–OP7) and all of them exhibited high scavenging activity, mainly against superoxide and hypochlorous acid species. OP1, OP2, and OP3 had the smallest minimal inhibitory concentration (MIC) against Gram-positive bacteria Streptococcus mutans, Streptococcus oralis, and Streptococcus aureus (12.5–100 μg/mL). OP1, OP2, OP3, and OP4 were more effective against Pseudomonas aeruginosa (Gram-negative), with MIC values ranging from 100 to 200 μg/mL. OP6 showed anti-inflammatory activity by decreasing NF-kB activation and TNF-α release in RAW 264.7 macrophages, and expressing the NF-κB-luciferase reporter stable gene. Therefore, south Brazilian OP can be considered an excellent source of bioactive compounds with great potential of application in the pharmaceutical and food industry. PMID:27802316

Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

PubMed Central

2010-01-01

Background Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. Methods The active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w. Results β-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 μM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects. Conclusion We found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future in vivo studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis. PMID:20525330

Synthesis and anti-inflammatory effect of chalcones and related compounds.

PubMed

Hsieh, H K; Lee, T H; Wang, J P; Wang, J J; Lin, C N

1998-01-01

Mast cell and neutrophil degranulations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2',5'-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone, 2'- and 3'-hydroxychalcones, 2',5'-dihydroxychalcones and flavanones were continually synthesized to evaluate their inhibitory effects on the activation of mast cells and neutrophils and the inhibitory effect on phlogist-induced hind-paw edema in mice. A series of chalcones and related compounds were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and the anti-inflammatory activities of these synthetic compounds were studied on inhibitory effects on the activation of mast cells and neutrophils. Some chalcones showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. Almost all chalcones and 4'-hydroxyflavanone exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Some chalcones showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP/cytochalasin B (CB) or phorbol myristate acetate (PMA). 2',3-Dihydroxy-, 2',5'-dihydroxy-4-chloro-, and 2',5'-dihydroxychalcone showed remarkable inhibitory effects on hind-paw edema induced by polymyxin B in normal as well as in adrenalectomized mice. These results indicated that the anti-inflammatory effects of these compounds were mediated, at least partly, through the suppression of chemical mediators released from mast cells and neutrophils.

Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

PubMed

Costa, Gustavo; Ferreira, João Pinto; Vitorino, Carla; Pina, Maria Eugénia; Sousa, João José; Figueiredo, Isabel Vitória; Batista, Maria Teresa

2016-02-03

A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analgesic, anti-inflammatory and anti-pyretic activities of Caesalpinia decapetala

PubMed Central

Parveen, Amna; Sajid Hamid Akash, Muhammad; Rehman, Kanwal; Mahmood, Qaisar; Qadir, Muhammad Imran

2014-01-01

Introduction: In many pathological conditions, pain, inflammation and fever are interdependent to each other. Due to the use of synthetic drugs, many unwanted effects usually appear. Various studies have been conducted on Caesalpinia decapetala (C. decapetala) to evaluate its effects in the treatment of various diseases but no sufficient scientific literature is available online to prove its analgesic, anti-inflammatory and anti-pyretic activities. Methods: The analgesic, anti-inflammatory and anti-pyretic activities of 70% aqueous methanolic and n-hexane extracts of C. decapetala was evaluated using Swiss albino mice (20-30 g). Results: The results showed that aqueous methanolic extract of C. decapetala at the dose of 100 mg/kg exhibited significant (p< 0.05) activities in various pain models including acetic acid-induced writhing (18.4 ± 0.53), formalin-induced licking (275 ± 4.18) and hot plate method (2.3 ± 0.0328); whereas,  n-hexane extract showed its effects in acetic acid-induced writhing (20 ± 0.31), formalin-induced licking (293 ± 1.20) and hot plate method (2.224 ± 0.029) compared to the effects observed in control group animals. Similarly, the aqueous methanolic extract of C. decapetala after 2 h of treatment exhibited more significant anti-inflammatory (0.66 ± 0.06) and anti-pyretic (38.81 ± 0.05) activities compared to the control group animals. Conclusion: From the findings of our present study, we concluded that the aqueous methanolic extract of C. decapetala has stronger analgesic, anti-inflammatory and anti-pyretic effects than its n-hexane extract. Further studies are required to investigate the active constituents of C. decapetala that exhibit analgesic, anti-inflammatory and anti-pyretic activities. PMID:24790898

Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice.

PubMed

Bansal, Shruti; Chhibber, Sanjay

2010-04-01

Acute lung injuries due to acute lung infections remain a major cause of mortality. Thus a combination of an antibiotic and a compound with immunomodulatory and anti-inflammatory activities can help to overcome acute lung infection-induced injuries. Curcumin derived from the rhizome of turmeric has been used for decades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatory properties by downregulation of various inflammatory mediators. Keeping these properties in mind, we investigated the anti-inflammatory properties of curcumin in a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillation of bacteria in this mouse model of acute pneumonia-induced inflammation resulted in a significant increase in neutrophil infiltration in the lungs along with increased production of various inflammatory mediators [i.e. malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), tumour necrosis factor (TNF)-alpha] in the lung tissue. The animals that received curcumin alone orally or in combination with augmentin, 15 days prior to bacterial instillation into the lungs via the intranasal route, showed a significant (P <0.05) decrease in neutrophil influx into the lungs and a significant (P <0.05) decrease in the production of MDA, NO, MPO activity and TNF-alpha levels. Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-alpha levels significantly (P >0.05) as compared to the control group. We therefore conclude that curcumin ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, curcumin can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in the case of acute lung infection.

Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation.

PubMed

Tang, Siah Ying; Sivakumar, Manickam; Ng, Angela Min-Hwei; Shridharan, Parthasarathy

2012-07-01

The present study investigated the anti-inflammatory and analgesic activities of novel aspirin oil-in-water (O/W) nanoemulsion and water-in-oil-in-water (W/O/W) nano multiple emulsion formulations generated using ultrasound cavitation techniques. The anti-inflammatory activities of nanoemulsion and nano multiple emulsion were determined using the λ-carrageenan-induced paw edema model. The analgesic activities of both nanoformulations were determined using acetic acid-induced writhing response and hot plate assay. For comparison, the effect of pretreatment with blank nanoemulsion and reference aspirin suspension were also studied for their anti-inflammatory and antinociceptive activities. The results showed that oral administration of nanoemulsion and nano multiple emulsion containing aspirin (60 mg/kg) significantly reduced paw edema induced by λ-carrageenan injection. Both nanoformulations decreased the number of abdominal constriction in acetic acid-induced writhing model. Pretreatment with nanoformulations led to a significant increase in reaction time in hot plate assay. Nanoemulsion demonstrated an enhanced anti-inflammatory and analgesic effects compared to reference suspension while nano multiple emulsion exhibited a mild inhibitory effects in the three experimental animal model tests. The results obtained for nano multiple emulsion were relatively lower than reference. However, administration of blank nanoemulsion did not alter the nociceptive response significantly though it showed slight anti-inflammatory effect. These experimental studies suggest that nanoemulsion and nano multiple emulsion produced a pronounced anti-inflammatory and analgesic effects in rats and may be candidates as new nanocarriers for pharmacological NSAIDs in the treatment of inflammatory disorders and alleviating pains. Copyright © 2012 Elsevier B.V. All rights reserved.

Trillin Reduces Liver Chronic Inflammation and Fibrosis in Carbon Tetrachloride (CCl4) Induced Liver Injury in Mice.

PubMed

Tan, Huabing; He, Qin; Li, Rugui; Lei, Feifei; Lei, Xu

2016-07-01

Trillin is an active ingredient isolated from Dioscorea nipponica Makino. This study investigated the anti-inflammatory and anti-fibrosis effects of trillin on CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation and fibrosis were induced by intraperitoneal administration of CCl4 0.5 μL/g of body weight twice a week for 6 weeks. Trillin (50 mg/kg, 100 mg/kg) was administered by gavage for 12 days before finishing the CCl4 induction. Aspartate amino-transferase (AST) and glutamic-pyruvic transaminase (ALT) in serum were determined by AST and ALT kits. Superoxidase dismutase (SOD) activity and malondialdehyde (MDA) levels in serum were assayed by SOD and MDA kits. Meanwhile, the levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay (ELISA) method. Pathological changes were observed by hematoxylin-eosin (HE) staining. The proteins of the NF-κB pathway and the TGF-β/Smad pathway were measured by western blot. The trillin-treated group exhibited reduced AST, ALT, MDA, IL-6, TNF-α, and IL-1β, and increased SOD. Histological analyses of the trillin-treated group exhibited reduced inflammatory process and prevented liver fibrosis. Western blot analyses of the trillin-treated group showed reduced NF-κB pathway and TGF-β/Smad pathway. Based on the results of the present study, trillin can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

Two new triterpene saponins from the anti-inflammatory saponin fraction of Ilex pubescens root.

PubMed

Wang, Jing-Rong; Zhou, Hua; Jiang, Zhi-Hong; Liu, Liang

2008-07-01

The saponin fraction from the ethanolic extracts of the root of Ilex pubescens Hook. et Arn. (Ilexaceae) was found to exhibit potent anti-inflammatory effects on carrageenan-induced paw edema in rats. Two novel triterpene saponins, pubescenosides C and D (1 and 2, resp.), together with five known saponins were isolated from this saponin fraction. The structures of 1 and 2 were elucidated as (20beta)-3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, and (20beta)-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa- 12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, respectively, on the basis of chemical and spectroscopic data. Five known saponins isolated from the saponin fraction were identified as ilexsaponin B(1), B(2), B(3), A(1), and chikusetsusaponin IV(a).

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.

Anti-oxidative assays as markers for anti-inflammatory activity of flavonoids.

PubMed

Chanput, Wasaporn; Krueyos, Narumol; Ritthiruangdej, Pitiporn

2016-11-01

The complexity of in vitro anti-inflammatory assays, the cost and time consumed, and the necessary skills can be a hurdle to apply to promising compounds in a high throughput setting. In this study, several antioxidative assays i.e. DPPH, ABTS, ORAC and xanthine oxidase (XO) were used to examine the antioxidative activity of three sub groups of flavonoids: (i) flavonol: quercetin, myricetin, (ii) flavanone: eriodictyol, naringenin (iii) flavone: luteolin, apigenin. A range of flavonoid concentrations was tested for their antioxidative activities and were found to be dose-dependent. However, the flavonoid concentrations over 50ppm were found to be toxic to the THP-1 monocytes. Therefore, 10, 20 and 50ppm of flavonoid concentrations were tested for their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated THP-1 monocytes. Expression of inflammatory genes, IL-1β, IL-6, IL-8, IL-10 and TNF-α was found to be sequentially decreased when flavonoid concentration increased. Principle component analysis (PCA) was used to investigate the relationship between the data sets of antioxidative assays and the expression of inflammatory genes. The results showed that DPPH, ABTS and ORAC assays have an opposite correlation with the reduction of inflammatory genes. Pearson correlation exhibited a relationship between the ABTS assay and the expression of three out of five analyzed genes; IL-1β, IL-6 and IL-8. Our findings indicate that ABTS assay can potentially be an assay marker for anti-inflammatory activity of flavonoids. Copyright © 2016 Elsevier B.V. All rights reserved.

A bioactive sesquiterpene from Bixa orellana.

PubMed

Raga, Dennis D; Espiritu, Rafael A; Shen, Chien-Chang; Ragasa, Consolacion Y

2011-01-01

A dichloromethane extract of the air-dried leaves of Bixa orellana afforded ishwarane 1, phytol 2, polyprenol 3, and a mixture of stigmasterol 4a and sitosterol 4b by silica gel chromatography. The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy. Compound 1 at three doses (25, 50, and 100 mg/kg BW) was tested for prophylactic, gastrointestinal motility, analgesic, hypoglycemic, and antimicrobial potentials. Results of the prophylactic assay demonstrated the anti-toxic property of 1 at 100 mg/kg BW. A 50 mg/kg BW dose of 1 resulted in a more propulsive movement of the gastrointestinal tract (88.38 ± 13.59%) compared to the negative control (78.47 ± 10.61%). Tail flick and acetic acid writhing tests indicated that 100 mg/kg BW 1 had minimal analgesic activity. Compound 1 demonstrated no hypoglycemic potential on the animals tested. Compound 1 exhibited moderate antifungal activity against C. albicans, low activity against T. mentagrophytes, and low antibacterial activity against E. coli, S. aureus, and P. aeruginosa. It was inactive against B. subtilis and A. niger.

Influences of Histidine-1 and Azaphenylalanine-4 on the Affinity, Anti-inflammatory, and Antiangiogenic Activities of Azapeptide Cluster of Differentiation 36 Receptor Modulators.

PubMed

Chignen Possi, Kelvine; Mulumba, Mukandila; Omri, Samy; Garcia-Ramos, Yesica; Tahiri, Houda; Chemtob, Sylvain; Ong, Huy; Lubell, William D

2017-11-22

Azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) exhibit promising affinity, selectivity, and modulator activity on the cluster of differentiation 36 receptor (CD36). For example, [A 1 , azaF 4 ]- and [azaY 4 ]-GHRP-6 (1a and 2b) were previously shown to bind selectively to CD36 and exhibited respectively significant antiangiogenic and slight angiogenic activities in a microvascular sprouting assay using choroid explants. The influences of the 1- and 4-position residues on the affinity, anti-inflammatory, and antiangiogenic activity of these azapeptides have now been studied in detail by the synthesis and analysis of a set of 25 analogues featuring Ala 1 or His 1 and a variety of aromatic side chains at the aza-amino acid residue in the 4-position. Although their binding affinities differed only by a factor of 17, the analogues exhibited significant differences in ability to modulate production of nitric oxide (NO) in macrophages and choroidal neovascularization.

Anti-Inflammatory Iridoids of Botanical Origin

PubMed Central

Viljoen, A; Mncwangi, N; Vermaak, I

2012-01-01

Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

Magnolol ameliorates lipopolysaccharide-induced acute lung injury in rats through PPAR-γ-dependent inhibition of NF-kB activation.

PubMed

Lin, Ming-Hsien; Chen, Meng-Chuan; Chen, Tso-Hsiao; Chang, Heng-Yuan; Chou, Tz-Chong

2015-09-01

Acute lung injury (ALI) has a high morbidity and mortality rate due to the serious inflammation and edema occurred in lung. Magnolol extracted from Magnolia officinalis, has been reported to exhibit anti-inflammatory, and antioxidant activities. Peroxisome proliferator-activated receptors (PPARs) are known to exert a cytoprotective effect against cellular inflammatory stress and oxidative injury. The aim of this study was to explore the involvement of PPAR-γ in the beneficial effect of magnolol in lipopolysaccharide (LPS)-induced ALI. We found that treatment with magnolol greatly improved the pathological features of ALI evidenced by reduction of lung edema, polymorphonuclear neutrophil infiltration, ROS production, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), the expression of iNOS and COX-2, and NF-κB activation in lungs exposed to LPS. Importantly, magnolol is capable of increasing the PPAR-γ expression and activity in lungs of ALI. However, blocking PPAR-γ activity with GW9662 markedly abolished the protective and anti-inflammatory effects of magnolol. Taken together, the present study provides a novel mechanism accounting for the protective effect of magnolol in LPS-induced ALI is at least partly attributed to induction of PPAR-γ in lungs, and in turn suppressing NF-κB-related inflammatory responses. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung

Highlights: Black-Right-Pointing-Pointer HBP sequence identified from HB-EGF has cell penetration activity. Black-Right-Pointing-Pointer HBP inhibits the NF-{kappa}B dependent inflammatory responses. Black-Right-Pointing-Pointer HBP directly blocks phosphorylation and degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer HBP inhibits nuclear translocation of NF-{kappa}B p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS),more » and cytokines (TNF-{alpha} and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-{alpha} and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-{kappa}B-dependent inflammatory responses by directly blocking the phosphorylation and degradation of I{kappa}B{alpha} and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-{kappa}B. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.« less

Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis.

PubMed

Bhui, Kulpreet; Tyagi, Shilpa; Srivastava, Amit Kumar; Singh, Madhulika; Roy, Preeti; Singh, Richa; Shukla, Yogeshwer

2012-03-01

Bromelain, obtained from pineapple, is already in use clinically as adjunct in chemotherapy. Our objective was to test its ability to act as a sole anti-cancer agent. Therefore, we describe its anti-proliferative, anti-inflammatory and subsequent anti-cancer effects in vitro, against human epidermoid carcinoma-A431 and melanoma-A375 cells. Bromelain exhibited reduction in proliferation of both these cell-lines and suppressed their potential for anchorage-independent growth. Further, suppression of inflammatory signaling by bromelain was evident by inhibition of Akt regulated-nuclear factor-kappaB activation via suppression of inhibitory-kappaBα phosphorylation and concomitant reduction in cyclooxygenase-2. Since, the inflammatory cascade is well-known to be closely allied to cancer; we studied the effect of bromelain on events/molecules central to it. Bromelain caused depletion of intracellular glutathione and generation of reactive oxygen-species followed by mitochondrial membrane depolarization. This led to bromelain-induced cell-cycle arrest at G(2)/M phase which was mediated by modulation of cyclin B1, phospho-cdc25C, Plk1, phospho-cdc2, and myt1. This was subsequently followed by induction of apoptosis, indicated by membrane-blebbing, modulation of Bax-Bcl-2 ratio, Apaf-1, caspase-9, and caspase-3; chromatin-condensation, increase in caspase-activity and DNA-fragmentation. Bromelain afforded substantial anti-cancer potential in these settings; hence we suggest it as a potential prospect for anti-cancer agent besides only an additive in chemotherapy. Copyright ©2011 Wiley Periodicals, Inc.

Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang increase LκB-α expression and ameliorate ulcerative colitis.

PubMed

Miao, X P; Sun, X N; Wei, H; Liu, Z J; Cui, L J; Deng, T Z

2015-02-01

The therapeutic potential of pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang in ulcerative colitis were investigated. This study showed that pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang ameliorated ulcerative colitis and were proposed to exhibit anti-inflammatory effects via increased expression of IκB-α proteins and suppressing NF-αB translocation.

Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines.

PubMed

Ahmad, Sheikh Fayaz; Attia, Sabry M; Bakheet, Saleh A; Zoheir, Khairy M A; Ansari, Mushtaq Ahmad; Korashy, Hesham M; Abdel-Hamied, Hala E; Ashour, Abdelkader E; Abd-Allah, Adel R A

2015-04-01

Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-β1, nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF-κB, STAT3 and COX-2 and decreased IκBα in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions.

Evaluation of anti-inflammatory activity of Vernonia cinerea Less. extract in rats.

PubMed

Mazumder, U K; Gupta, M; Manikandan, L; Bhattacharya, S; Haldar, P K; Roy, S

2003-03-01

The methanol extract of the whole plant of Vernonia cinerea Less. was evaluated for its anti-inflammatory activity in acute (carrageenin, histamine and serotonin induced rat paw edema) and a chronic model (cotton pouch induced granuloma). The methanol extract (250 and 500 mg/kg(-1) p.o.) exhibited significant activity (p < 0.001) against all phlogistic agents used in a dose dependant manner. In the chronic model (cotton pouch granuloma method) the methanol extract exhibited significant anti-inflammatory activity. All these effects were compared with standard drug phenylbutazone (100 mg/kg(-1) p.o.).

Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages.

PubMed

Lu, Sheng-Hua; Hsu, Wen-Lin; Chen, Tso-Hsiao; Chou, Tz-Chong

2015-12-01

Magnolol isolated from Magnolia officinalis, a Chinese medical herb, exhibits an anti-inflammatory activity and a protective effect against periodontitis. The inflammation caused by lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) has been considered a key inducer in the development of periodontitis. In this study, we investigated whether magnolol inhibits P. gingivalis LPS-evoked inflammatory responses in RAW 264.7 macrophages and the involvement of heme oxygenase-1 (HO-1). Magnolol significantly activated p38 MAPK, Nrf-2/HO-1 cascade and reactive oxygen species (ROS) formation. Notably, the Nrf-2 activation and HO-1 induction by magnolol were greatly diminished by blocking p38 MAPK activity and ROS production. Furthermore, in P. gingivalis LPS-stimulated macrophages, magnolol treatment remarkably inhibited the inflammatory responses evidenced by suppression of pro-inflammatory cytokine, prostaglandin E2, nitrite formation, and the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as NF-κB activation accompanied by a significant elevation of Nrf-2 nuclear translocation and HO-1 expression/activity. However, inhibiting HO-1 activity with tin protoporphyrin IX markedly reversed the anti-inflammatory effects of magnolol. Collectively, these findings provide a novel mechanism by which magnolol inhibits P. gingivalis LPS-induced inflammation in macrophages is at least partly mediated by HO-1 activation, and thereby promoting its clinical use in periodontitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Antinociceptive and Anti-Inflammatory Activities of Bridelia retusa Methanolic Fruit Extract in Experimental Animals

PubMed Central

Kumar, Tekeshwar; Jain, Vishal

2014-01-01

Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (P < 0.001). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract. PMID:25506619

Anti-nociceptive activity of Pereskia bleo Kunth. (Cactaceae) leaves extracts.

PubMed

Abdul-Wahab, Ikarastika Rahayu; Guilhon, Carolina Carvalho; Fernandes, Patricia Dias; Boylan, Fabio

2012-12-18

Local communities in Malaysia consume Pereskia bleo Kunth. (Cactaceae) leaves as raw vegetables or as a concoction and drink as a tea to treat diabetes, hypertension, rheumatism, cancer-related diseases, inflammation, gastric pain, ulcers, and for revitalizing the body. To evaluate anti-nociceptive activity of the extracts and vitexin, isolated for the first time in this species, in two analgesic models; formalin-induced licking and acetic acid-induced abdominal writhing. Three and a half kilos of P. bleo leaves were extracted using Soxhlet apparatus with ethanol for 72 h. The crude ethanol extract was treated with activated charcoal overnight and subjected to a liquid-liquid partition yielding hexane, dichloromethane, ethyl acetate and butanol extracts. All extracts, including the crude ethanol and vitexin isolated from the ethyl acetate partition were tested for peripheral anti-nociceptive activity using formalin test and acetic acid-induced abdominal writhing, besides having their acute toxicity assays performed. The phytochemical analyses resulted in the isolation of vitexin (1), β-sitosterol glucoside (2) and β-sitosterol (3) isolated from the ethyl acetate, dichloromethane and hexane extracts, respectively. This is the first time vitexin and β-sitosterol glucoside are isolated from this species. The anti-nociceptive activities for all extracts were only moderate. Vitexin, which was isolated from the ethyl acetate extract did not show any activity in all models tested when used alone at the same concentration as it appears in the extract. This study showed that all the extracts possess moderate anti-nociceptive activity. Vitexin is not the compound responsible for the anti-nociceptive effect in the ethyl acetate extract. Further investigations are needed to identify the compound(s) that might be responsible for the anti-nociceptive activity in this plant. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The lysosome among targets of metformin: new anti-inflammatory uses for an old drug?

PubMed

Lockwood, Thomas D

2010-05-01

Rheumatoid arthritis and type-2 diabetes exhibit progressive co-morbidity. Chloroquine (CQ) reportedly improves both. CQ inhibits lysosomal function in cultured cells at supra-therapeutic concentration; however, this is doubted as target mechanism. Some anti-diabetic biguanides are metal-interactive lysosomal inhibitors; and all bind Zn(2+). i) To bioassay the potency of CQ using (3)H-leucine release from perfused myocardial tissue. ii) To determine whether metformin (MET) is CQ-mimetic, and interactive with Zn(2+). Therapeutic CQ concentration (0.1 - 0.5 microM) clearly does cause lysosomal inhibition although delayed and submaximal. MET alone (10 microM) caused sub-maximal inhibition. Supra-physiological extracellular Zn(2+) (5 - 50 microM) alone increased tissue Zn(2+) content, and inhibited lysosomal proteolysis. Physiological equivalent Zn(2+) (approximately 1 microM) had no effect. MET (

C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice.

PubMed

Kimura, Toru; Nojiri, Takashi; Hino, Jun; Hosoda, Hiroshi; Miura, Koichi; Shintani, Yasushi; Inoue, Masayoshi; Zenitani, Masahiro; Takabatake, Hiroyuki; Miyazato, Mikiya; Okumura, Meinoshin; Kangawa, Kenji

2016-02-19

Pulmonary fibrosis has high rates of mortality and morbidity; however, no effective pharmacological therapy has been established. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, selectively binds to the transmembrane guanylyl cyclase (GC)-B receptor and exerts anti-inflammatory and anti-fibrotic effects in various organs through vascular endothelial cells and fibroblasts that have a cell-surface GC-B receptor. Given the pathophysiological importance of fibroblast activation in pulmonary fibrosis, we hypothesized that the anti-fibrotic and anti-inflammatory effects of exogenous CNP against bleomycin (BLM)-induced pulmonary fibrosis were exerted in part by the effect of CNP on pulmonary fibroblasts. C57BL/6 mice were divided into two groups, CNP-treated (2.5 μg/kg/min) and vehicle, to evaluate BLM-induced (1 mg/kg) pulmonary fibrosis and inflammation. A periostin-CNP transgenic mouse model exhibiting CNP overexpression in fibroblasts was generated and examined for the anti-inflammatory and anti-fibrotic effects of CNP via fibroblasts in vivo. Additionally, we assessed CNP attenuation of TGF-β-induced differentiation into myofibroblasts by using immortalized human lung fibroblasts stably expressing GC-B receptors. Furthermore, to investigate whether CNP acts on human lung fibroblasts in a clinical setting, we obtained primary-cultured fibroblasts from surgically resected lungs of patients with lung cancer and analyzed levels of GC-B mRNA transcription. CNP reduced mRNA levels of the profibrotic cytokines interleukin (IL)-1β and IL-6, as well as collagen deposition and the fibrotic area in lungs of mice with bleomycin-induced pulmonary fibrosis. Furthermore, similar CNP effects were observed in transgenic mice exhibiting fibroblast-specific CNP overexpression. In cultured-lung fibroblasts, CNP treatment attenuated TGF-β-induced phosphorylation of Smad2 and increased mRNA and protein expression of α-smooth muscle actin and SM22α, indicating that CNP suppresses fibroblast differentiation into myofibroblasts. Furthermore, human lung fibroblasts from patients with or without interstitial lung disease substantially expressed GC-B receptor mRNA. These data suggest that CNP ameliorates bleomycin-induced pulmonary fibrosis by suppressing TGF-β signaling and myofibroblastic differentiation in lung fibroblasts. Therefore, we propose consideration of CNP for clinical application to pulmonary fibrosis treatment.

Dehydrated Basella alba Fruit Juice as a Novel Natural Colorant: Pigment Stability, In Vivo Food Safety Evaluation and Anti-Inflammatory Mechanism Characterization.

PubMed

Huang, Fu-Long; Chiou, Robin Y-Y; Chen, Wei-Cheng; Ko, Huey-Jiun; Lai, Li-Jung; Lin, Shu-Mei

2016-09-01

Flesh of Basella alba L. mature fruits bearing deep-violet juice provides a novel and potential source of natural colorant. To minimize the pigment purification process and warrant safety acceptability, B. alba colorant powder (BACP) was prepared using mature fruits through a practical batch preparation and subjected to fundamental pigment characterization, food safety assessment and bio-function evaluation. Yield of the dehydrated B. alba colorant powder (BACP) was 37 g/kg fresh fruits. Reconstituted aqueous solution of the BACP exhibited an identical visible spectrum (400-700 nm) as that of fresh juice. Color of the solution (absorbance at 540 nm) was stable in a broad pH ranged from 3 to 8 and enhanced by co-presence of calcium and magnesium ions, while was rapidly bleached by ferrous and ferric ions. For in vivo food safety evaluation, ICR mice were daily gavage administered with BACP up to 1000 mg/kg body weight for 28 days. Organ weight determination, serum biochemical analysis and histopathological examination of hearts, livers, lungs and kidneys revealed no obvious health hazard. In vitro anti-inflammatory activity of BACP was characterized in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. BACP exerted potent anti-inflammatory activity by down-regulation of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α, IL-1β, IL-6 and IL-12 and the blockage of IκB kinase (IKK)/IκB/nuclear factor-κ B (NFκB) activation cascade. These results supported that BACP may serve as a beneficial alternative of natural food colorant.

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

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

Fang, Qilu; Diabetes Center and Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang; Wang, Jingying

High glucose-induced inflammatory response in diabetic complications plays an important role in disease occurrence and development. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be a new avenue for treating diabetic complications. Chalcones are a class of natural products with various pharmacological activities. Previously, we identified L2H17 as a chalcone with good anti-inflammatory activity, inhibiting LPS-induced inflammatory response in macrophages. In this study, we examined L2H17's effect on hyperglycemia-induced inflammation both in mouse peritoneal macrophages and a streptozotocin-induced T1D mouse model. Our results indicate that L2H17 exhibits a strong inhibitory effect on the expression of pro-inflammatorymore » cytokines, cell adhesion molecules, chemokines and macrophage adhesion via modulation of the MAPK/NF-κB pathway. Furthermore, in vivo oral administration of L2H17 resulted in a significant decrease in the expression of pro-inflammatory cytokines and cell adhesion molecules, contributing to a reduction of key markers for renal and cardiac dysfunction and improvements in fibrosis and pathological changes in both renal and cardiac tissues of diabetic mice. These findings provide the evidence supporting targeting MAPK/NF-κB pathway may be effective therapeutic strategy for diabetic complications, and suggest that L2H17 may be a promising anti-inflammatory agent with potential as a therapeutic agent in the treatment of renal and cardiac diabetic complications. - Highlights: • Chalcones are a class of natural products with various pharmacological activities. • We identified L2H17 a chalcone with good anti-inflammatory activity. • L2H17 improved histological abnormalities both in diabetic heart and kidney. • L2H17 reduced inflammatory responses in HG-stimulated mouse peritoneal macrophages. • MAPKs/NF-κB pathway may be a promising therapeutic target for diabetic complications.« less

Upregulation of heme oxygenase-1 mediates the anti-inflammatory activity of casein glycomacropeptide (GMP) hydrolysates in LPS-stimulated macrophages.

PubMed

Li, Tiange; Cheng, Xue; Du, Min; Chen, Bin; Mao, Xueying

2017-07-19

Recently, we have shown that casein glycomacropeptide hydrolysates (GHP) exhibit both anti-inflammatory and anti-oxidative activities in vitro. However, whether heme oxygenase-1 (HO-1) is involved in the cytoprotective effect of GHP against the inflammatory status remains unclear. Therefore, we hypothesized that HO-1 is a potential target of GHP, which mediates its anti-inflammatory effect. Here, GHP inhibited the intracellular reactive oxygen species (ROS) accumulation and NADPH oxidase 2 (NOX2) expression and enhanced reduced glutathione (GSH) levels in LPS-stimulated RAW264.7 macrophages. GHP also suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) stimulated by lipopolysaccharide (LPS). However, zinc(ii)-protoporphyrin IX (ZnPPIX), a selective inhibitor of HO-1, restored the GHP-mediated suppression of ROS production and NOX2, TNF-α, IL-1β, IL-6 and iNOS expression. GHP treatment inhibited the LPS-induced nuclear transcription factor kappa-B (NF-κB) translocation, which was markedly reversed by ZnPPIX. Furthermore, GHP induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and p38. Pharmacological inhibition of Akt, ERK1/2, and p38 abrogated GHP-induced nuclear localization of NF-E2-related factor-2 (Nrf2) and the expression of HO-1. In summary, GHP inhibits the LPS-induced inflammatory status through upregulating HO-1 expression via PI3K/Akt, ERK1/2 and p38 signaling pathways in RAW264.7 macrophages.

Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.

PubMed

Liang, Jiali; Dou, Yaoxing; Wu, Xue; Li, Huilin; Wu, Jiazhen; Huang, Qionghui; Luo, Dandan; Yi, Tiegang; Liu, Yuhong; Su, Ziren; Chen, Jianping

2018-03-01

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE 2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense. Copyright © 2018 Elsevier B.V. All rights reserved.

Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil.

PubMed

Bashir, Samina; Ali, Shakir; Khan, Farah

2015-01-01

The present study was designed to assess the potential of supplementation of diet with Flaxseed (Linum usitatissimum, L.) oil (FXO), on obesity-related inflammation and reversal of obesity-induced insulin resistance. Swiss Albino mice, C57bl/6 mice and co-culture of 3T3-L1 adipocytes - RAW 264.7 macrophages to mimick obese adipose tissue environment were used for the study. Oral gavage of FXO at concentrations of 4, 8 or 16 mg/kg body weight (bwt) for 4 weeks or high-fat diet (HFD, 60% energy as fat) supplemented with dietary FXO (4, 8 or 16 mg/kg bwt) was given to the mice. FXO was characterised using gas chromatography - mass spectrometry. FXO supplemented HFD-fed mice (4 mg/kg bwt exhibited reduced adiposity index, serum glucose levels and triglycerides (8 and 16 mg/kg bwt) and improvement in insulin sensitisation (4, 8 and 16 mg/kg bwt) when compared with HFD mice. The co-culture showed a dose-dependent shift in cytokines towards anti-inflammatory (IL-4) state, with a decrease in pro-inflammatory TNF-α (p < 0.05). For immunomodulatory studies a dose-dependent increase (p < 0.05) was observed in antigen-specific levels of Th2 (IL-4) cytokine, serum anti-ova IgG1 and IgE levels. Suppression in anti-ova IgG2a, IgG2b, and IgG3 and antigen-specific Th1 cytokines like TNF-α and IFN-γ significantly (p < 0.05) was observed at 16 mg/kg bwt dosage. The results indicate that FXO exhibits an anti-inflammatory immunomodulatory potential and may partially relieve symptoms of obesity-associated insulin resistance.

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

Xu, Guang-Lin; Department of Pharmacology, University of Michigan, Ann Arbor; Du, Yi-Fang

KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the anti-inflammatory activity test focusing on its modulation of inflammatory mediators as well as intracellular MAPK and NF-κB signaling pathways. In acute ear edema model, pretreatment with KYKZL-1 (p.o.) dose-dependently inhibited the xylene-induced ear edema in mice with a higher inhibition than diclofenac. In a three-day TPA-induced inflammation, KYKZL-1 also showed significant anti-inflammatory activity with inhibition ranging between 20% and 64%. In gastric lesion test, KYKZL-1 elicited markedly fewer stomach lesions with a low index of ulcer as compared to diclofenac in rats. In further studies, KYKZL-1 wasmore » found to significantly inhibit the production of NO, PGE{sub 2}, LTB{sub 4} in LPS challenged RAW264.7, which is parallel to its attenuation of the expression of iNOS, COX-2, 5-LOX mRNAs or proteins and inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-κB. Taken together, our data indicate that KYKZL-1 comprises dual inhibition of COX and 5-LOX and exerts an obvious anti-inflammatory activity with an enhanced gastric safety profile via simultaneous inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-κB. - Highlights: • KYKZL-1 is designed to exhibit COX/5-LOX dual inhibition. • KYKZL-1 inhibits NO, PGE{sub 2} and LTB{sub 4} and iNOS, COX-2 and 5-LOX mRNAs and MAPKs. • KYKZL-1 inhibits phosphorylation of MAPKs. • KYKZL-1 inactivates NF-κB pathway.« less

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

PubMed

Moussaieff, Arieh; Shohami, Esther; Kashman, Yoel; Fride, Ester; Schmitz, M Lienhard; Renner, Florian; Fiebich, Bernd L; Munoz, Eduardo; Ben-Neriah, Yinon; Mechoulam, Raphael

2007-12-01

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-kappaB activation. It had no effect on IKK activity in vitro, and it did not suppress IkappaB alpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-kappaB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFalpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

PubMed

Koksal, Meric; Ozkan-Dagliyan, Irem; Ozyazici, Tugce; Kadioglu, Beril; Sipahi, Hande; Bozkurt, Ayhan; Bilge, Suleyman S

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively. © 2017 Deutsche Pharmazeutische Gesellschaft.

The Anticancer Activity of Sea Buckthorn [Elaeagnus rhamnoides (L.) A. Nelson].

PubMed

Olas, Beata; Skalski, Bartosz; Ulanowska, Karolina

2018-01-01

Various parts of sea buckthorn [ Elaeagnus rhamnoides (L.) A. Nelson], particularly the berries, known also as seaberries, or Siberian pineapples, are characterized by a unique composition of bioactive compounds: phenolic compounds, vitamins (especially vitamin C), unsaturated fatty acids, and phytosterols such as beta-sitosterol. These berries, together with the juices, jams, and oils made from them, have a range of beneficial antioxidant, anti-inflammatory, and anticancer effects. This short review discusses whether sea buckthorn may represent a "golden mean" for the treatment of cancers: It has anti-proliferation properties and can induce apoptosis and stimulate the immune system, and sea buckthorn oil counteracts many side effects of chemotherapy by restoring kidney and liver function, increasing appetite, and keeping patients in general good health. Although the anticancer activity of sea buckthorn has been confirmed by many in vitro and animal in vivo studies, the treatment and prophylactic doses for humans are unknown. Therefore, greater attention should be paid to the development of well-controlled and high-quality clinical experiments in this area.

Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents.

PubMed

Won, Shen-Jeu; Liu, Cheng-Tsung; Tsao, Lo-Ti; Weng, Jing-Ru; Ko, Horng-Huey; Wang, Jih-Pyang; Lin, Chun-Nan

2005-01-01

In an effort to develop potent anti-inflammatory and cancer chemopreventive agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde or prepared with appropriate dihydrochalcone reacted with appropriate alkyl bromide or prepared in one-pot procedure involving acetophenone and convenient aromatic aldehyde using ultrasonic agitation on basic alumina. The synthesized products were tested for their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. The potent inhibitors of NO production in macrophages and microglial cells were further evaluated for their in vitro cytotoxic effects against several human cancer cell lines. 2'-Hydroxychalcones 1-3, and 2',5'-dihydroxychalcone 7 exhibited potent inhibitory effects on the release of beta-glucuronidase or lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Two 2'-hydroxychalcones (1 and 3) showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. The previously reported chalcone, 5, 6, and 12, exhibited potent inhibitory effect on NO production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells or in LPS-activated RAW 264.7 macrophage-like cells. The potent inhibitors 5, 6, and 12 of NO production in macrophages or microglial cells revealed significant or marginal cytotoxic effects against several human cancer lines. Compound 12 manifested potent selective cytotoxicity against human MCF-7 cells and caused cell death by apoptosis. The present results demonstrated that 1-3, and 7 have anti-inflammatory effects and 5, 6, and 12 are potential anti-inflammatory and cancer chemopreventive agents.

Anti-inflammatory activity of Pistacia lentiscus essential oil: involvement of IL-6 and TNF-alpha.

PubMed

Maxia, Andrea; Sanna, Cinzia; Frau, Maria Assunta; Piras, Alessandra; Karchuli, Manvendra Singh; Kasture, Veena

2011-10-01

The topical anti-inflammatory activity of essential oil of Pistacia lentiscus L. was studied using carrageenan induced rat paw edema and cotton pellet induced granuloma. The effect on serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats inserted with cotton pellet was also investigated. On topical application, the oil exhibited a significant decrease in paw edema. The oil also inhibited cotton pellet-induced granuloma, and reduced serum TNF-alpha and IL-6. It can be concluded that the essential oil of Pistacia lentiscus reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

Pinocembrin, a novel histidine decarboxylase inhibitor with anti-allergic potential in in vitro.

PubMed

Hanieh, Hamza; Hairul Islam, Villianur Ibrahim; Saravanan, Subramanian; Chellappandian, Muthiah; Ragul, Kessavane; Durga, Arumugam; Venugopal, Kaliyamoorthy; Senthilkumar, Venugopal; Senthilkumar, Palanisamy; Thirugnanasambantham, Krishnaraj

2017-11-05

Pinocembrin (5, 7- dihydroxy flavanone) is the most abundant chiral flavonoid found in propolis, exhibiting antioxidant, antimicrobial and anti-inflammatory properties. However, the effect of Pinocembrin on allergic response is unexplored. Thus, current study aimed at investigating the effects of Pinocembrin on IgE-mediated allergic response in vitro. A special emphasis was directed toward histidine decarboxylase (HDC) and other pro-allergic and pro-inflammatory mediators. Preliminary studies, using a microbiological model of Klebsiella pneumoniae, provided first evidences that suggest Pinocembrin as a potential thermal stable inhibitor for HDC. Applying docking analysis revealed possible interaction between Pinocembrin and mammalian HDC. In vitro studies validated the predicted interaction and showed that Pinocembrin inhibits HDC activity and histamine in IgE-sensitized RBL-2H3 in response to dinitrophenol (DNP)-bovine serum albumin (BSA) stimulation. In addition, Pinocembrin mitigated the damage in the mitochondrial membrane, formation of cytoplasmic granules and degranulation as indicated by lower β-hexoseaminidase level. Interestingly, it reduced range of pro-inflammatory mediators in the IgE-mediated allergic response including tumor necrosis factor (TNF)-α, interleukin (IL)-6, nitric oxide (NO), inducible NO synthase (iNOS), phosphorylation of inhibitory kappa B (IкB)-α, prostaglandin (PGE)-2 and cyclooxygenase (COX)-2. In conclusion, current study suggests Pinocembrin as a potential HDC inhibitor, and provides the first evidences it is in vitro anti-allergic properties, suggesting Pinocembrin as a new candidate for natural anti-allergic drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Report: complexation of β-sitosterol with tris (dibenzylideneacetone) dipalladium and its anti-microbial activity.

PubMed

Mahmood, Talat; Bibi, Yasmeen; Zafar, Raana; Wahab, Aneela; Mahmood, Iffat; Arshad, Nuzhat; Sherwani, Sikandar Khan

2015-03-01

β-sitosterol is a naturally occurring plant sterol (phytosterol) present in many fruits and vegetables. Scientific research has proven that β-sitosterol is helpful in maintaining the proper functioning of our body. Previously we described the complexation of β-sitosterol with trace metals (Mahmood et al., 2013). Trace metals after the formation of complex unable to absorb in the body and hence eliminated out from the body thus reducing metal toxicity (Marsha, 1996). The present article describes the complexation of μ-sitosterol with Palladium (Pd) metal. Palladium is a toxic metal and due to polluted and hazardous environment traces of this metal can be transferred into the body, which is harmful for human health. Our aim is to make Pd-sterol complex so that this toxic metal (Pd) does not absorb in the body and hence excreted out from the body in the complex form. In order to form this complex μ-sitosterol (Ib) is reacted with Tris (dibenzylideneacetone) dipalladium or [Pd(2) (DBA)(3)] (Ia) in 2:1 ratio in an inert atmosphere and dimethylformamid (DMF) added as a solvent. The resulting complex [Pd(2) (DBA)(3).(β-sitosterol) (Ic) was identified by various spectroscopic techniques such as IR, Mass and (1)H-NMR. This new organo metallic complex (Ic) also showed significant antibacterial and antifungal activity. The present work revealed that Pd-sterol complex does not only reduce metal toxicity but also helpful in minimizing bacterial and fungal infections present in the body. Our research also concluded that we must take plenty of fruits and vegetables in our diet so that natural plant sterol such as β-sitosterol can enhance our defense mechanism and maintain other functions of our body.

Cynaropicrin: A Comprehensive Research Review and Therapeutic Potential As an Anti-Hepatitis C Virus Agent

PubMed Central

Elsebai, Mahmoud F.; Mocan, Andrei; Atanasov, Atanas G.

2016-01-01

The different pharmacologic properties of plants-containing cynaropicrin, especially artichokes, have been known for many centuries. More recently, cynaropicrin exhibited a potential activity against all genotypes of hepatitis C virus (HCV). Cynaropicrin has also shown a wide range of other pharmacologic properties such as anti-hyperlipidemic, anti-trypanosomal, anti-malarial, antifeedant, antispasmodic, anti-photoaging, and anti-tumor action, as well as activation of bitter sensory receptors, and anti-inflammatory properties (e.g., associated with the suppression of the key pro-inflammatory NF-κB pathway). These pharmacological effects are very supportive factors to its outstanding activity against HCV. Structurally, cynaropicrin might be considered as a potential drug candidate, since it has no violations for the rule of five and its water-solubility could allow formulation as therapeutic injections. Moreover, cynaropicrin is a small molecule that can be easily synthesized and as the major constituent of the edible plant artichoke, which has a history of safe dietary use. In summary, cynaropicrin is a promising bioactive natural product that, with minor hit-to-lead optimization, might be developed as a drug for HCV. PMID:28008316

Design and in vitro evaluation of self-assembled indometacin prodrug nanoparticles for sustained/controlled release and reduced normal cell toxicity

NASA Astrophysics Data System (ADS)

Lin, Jinyan; Pan, Zhou; Song, Liang; Zhang, Yanmei; Li, Yang; Hou, Zhenqing; Lin, Changjian

2017-12-01

Despite the great efficacy of indomethacin (IND) as an anti-inflammatory agent, its clinical translation has been obstructed by the water insolubility, severe side effects, and exceedingly low bioavailability. Indomethacin prodrug-based nanoparticles (NPs) combining the strengths of both nanotechnology and prodrugs that might overcome this crucial problem are presented. Here, using the carbodiimide-mediated couple reaction, IND was conjugated to clinically approved poly(ethylene glycol) (PEG) polymer via peptide linkage that was cleavaged in the presence of cathepsin B, which was significantly induced after inflammatory. The synthesized IND-PEG-IND conjugate was characterized by UV-vis, FTIR, 1H NMR, XRD, and MALDI-TOF-MS analyses. For its intrinsic amphiphilic property, the IND prodrug self-assembled into NPs in aqueous solution and served two roles-as an anti-inflammatory prodrug and a drug carrier. The constructed IND-PEG-IND NPs had naoscaled particle size of approximately 80 nm, negative surface, spherical shape, good water-dispersity, and high and fixed drug-loading content of 20.1 wt%. In addition, IND-PEG-IND NPs demonstrated sustained and cathepsin B-controlled drug release behavior. More importantly, IND-PEG-IND NPs significantly reduced the acute totoxicity agaist normal osteoblast cells and displayed the more potent anti-inflammatory effect against macrophage cells compared to the free IND. Taken together, the nanoprodrug might exhibit increased potency for nanomedicine-prospective therapeutic use in clinical treatement of implant inflammatory diseases.

Oxazolo[4,5-b]pyridine-Based Piperazinamides as GSK-3β Inhibitors with Potential for Attenuating Inflammation and Suppression of Pro-Inflammatory Mediators.

PubMed

Tantray, Mushtaq A; Khan, Imran; Hamid, Hinna; Alam, Mohammad Sarwar; Dhulap, Abhijeet; Ganai, Ajaz Ahmad

2017-08-01

Recent studies reveal that glycogen synthase kinase-3β (GSK-3β) acts as a pro-inflammatory enzyme, and by inhibiting this kinase, inflammation can be controlled. In this regard, a series of 17 piperazine-linked oxazolo[4,5-b]pyridine-based derivatives was synthesized and evaluated for in vitro GSK-3β inhibitory and in vivo anti-inflammatory activity. The compounds 7d, 7e, 7g, and 7c displayed the best GSK-3β inhibitory activity among all the synthesized compounds, with corresponding IC 50 values of 0.34, 0.39, 0.47, and 0.53 µM. Among the compounds 7d, 7e, 7g, and 7c examined for in vivo anti-inflammatory activity in the rat paw edema model, compound 7d exhibited maximum inhibition, reducing the paw volume by 62.79 and 65.91% at 3 and 5 h post-carrageenan administration, respectively, in comparison to indomethacin (76.74% at 3 h and 79.54% at 5 h after carrageenan administration). Furthermore, these compounds (7d, 7e, 7g, and 7c) were also found to substantially inhibit pro-inflammatory mediators, i.e., TNF-α, IL-1β, and IL-6, ex vivo in comparison to indomethacin and did not pose any gastric ulceration risk, indicating the potential of this oxazolopyridine scaffold for the development of GSK-3β inhibitors and their application as anti-inflammatory agents. © 2017 Deutsche Pharmazeutische Gesellschaft.

The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches

PubMed Central

Espírito-Santo, Renan Fernandes; Meira, Cassio Santana; Costa, Rafael dos Santos; Souza Filho, Otávio Passos; Evangelista, Afranio Ferreira; Trossini, Gustavo Henrique Goulart; Ferreira, Glaucio Monteiro; Velozo, Eudes da Silva; Pereira Soares, Milena Botelho

2017-01-01

Braylin belongs to the group of natural coumarins, a group of compounds with a wide range of pharmacological properties. Here we characterized the pharmacological properties of braylin in vitro, in silico and in vivo in models of inflammatory/immune responses. In in vitro assays, braylin exhibited concentration-dependent suppressive activity on activated macrophages. Braylin (10–40 μM) reduced the production of nitrite, IL-1β, TNF-α and IL-6 by J774 cells or peritoneal exudate macrophages stimulated with LPS and IFN-γ. Molecular docking calculations suggested that braylin present an interaction pose to act as a glucocorticoid receptor ligand. Corroborating this idea, the inhibitory effect of braylin on macrophages was prevented by RU486, a glucocorticoid receptor antagonist. Furthermore, treatment with braylin strongly reduced the NF-κB-dependent transcriptional activity on RAW 264.7 cells. Using the complete Freund’s adjuvant (CFA)-induced paw inflammation model in mice, the pharmacological properties of braylin were demonstrated in vivo. Braylin (12.5–100 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on CFA model. Braylin did not produce antinociception on the tail flick and hot plate tests in mice, suggesting that braylin-induced antinociception is not a centrally-mediated action. Braylin exhibited immunomodulatory properties on the CFA model, inhibiting the production of pro-inflammatory cytokines IL-1β, TNF-α and IL-6, while increased the anti-inflammatory cytokine TGF-β. Our results show, for the first time, anti-inflammatory, antinociceptive and immunomodulatory effects of braylin, which possibly act through the glucocorticoid receptor activation and by inhibition of the transcriptional activity of NF-κB. Because braylin is a phosphodiesterase-4 inhibitor, this coumarin could represent an ideal prototype of glucocorticoid receptor ligand, able to induce synergic immunomodulatory effects. PMID:28594906

A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

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

Fang, Qilu; Zhao, Leping; Wang, Yi

Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52Emore » cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.« less

Mangiferin ameliorates Porphyromonas gingivalis-induced experimental periodontitis by inhibiting phosphorylation of nuclear factor-κB and Janus kinase 1-signal transducer and activator of transcription signaling pathways.

PubMed

Li, H; Wang, Q; Ding, Y; Bao, C; Li, W

2017-02-01

Mangiferin is a natural polyphenol compound with anti-inflammatory properties. However, there have been few reports on the effect of mangiferin on periodontitis. Here, we investigated the anti-inflammatory effects of this compound on experimental periodontitis and the underlying mechanisms. Mice were inoculated with Porphyromonas gingivalis to induce periodontitis, and treated with mangiferin orally (50 mg/kg bodyweight, once a day) for 8 wk. Then, the alveolar bone loss was examined using a scanning electronic microscope. Expression of tumor necrosis factor-α (TNF-α) and the phosphorylation levels of nuclear factor-κB (NF-κB) and Janus kinase 1-signal transducer and activator of adhesion (JAK1-STAT) pathways in the gingival epithelium were detected using western blot analysis and immunohistochemical staining. The results showed that mice with periodontitis exhibited greater alveolar bone loss, stronger expression of TNF-α and higher phosphorylation levels of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia, compared with control mice with no periodontitis. Moreover, treatment with mangiferin could significantly inhibit alveolar bone loss, TNF-α production and phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia. Mangiferin has anti-inflammatory effects on periodontitis, which is associated with its ability to down-regulate the phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways

PubMed Central

Mandal, Animesh; Bhatia, Deepak; Bishayee, Anupam

2017-01-01

Pomegranate (Punica granatum L.), a nutrient-rich unique fruit, has been used for centuries for the prevention and treatment of various inflammation-driven diseases. Based on our previous study, a characterized pomegranate emulsion (PE) exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms. The objective of the present work is to investigate the anti-inflammatory mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2–5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis. These findings, together with our previous results, indicate that PE-mediated prevention of DMBA-evoked mammary carcinogenesis may involve anti-inflammatory mechanisms through concurrent but differential regulation of two interrelated molecular pathways, namely NF-κB and Nrf2 signaling. PMID:28452959

Anti-inflammatory, anti-bacterial activity and structure-activity relationships of substitutions on 4-thiazolidinone derivatives - Part-1.

PubMed

Naeem, Muhammad; Chadhury, Muhammad Nawaz; Amjad, Rana; Rehaman, Salma; Khan, Kahlida

2012-10-01

Environmentally benign and economically feasible procedures have been adopted for the synthesis of novel biologically potential 4-thiazolidinone derivatives. Purpose built microwave oven and ionic liquids (PTCs) showed wrack improvements in yield, time and cost. The yield of 1st series (01-08) obtained in the ranged from 82.4-94.2% and for 2nd series (09-16) obtained 80.6-92.8%. The compounds (01-16) were applied for anti-inflammatory activity at concentrations of 0.5 and 01 mg/kg in carrageenan induced acute and formalin induced chronic inflammatory procedures in mice and better results were obtained at 0.5 mg/kg dose. Some of the compounds 03, 04, 07, 12, 13 showed remarkable anti-inflammatory activity in both procedures as compared to the standard reference drug 2-(2,6-dichloranilino) phenyl acetic acid (diclofenac). Particularly compound 12 and 13 may be used as a non-steroidal anti-inflammatory drug (NSAID) to reduce inflammation. The compounds (01-16) were screened for their antimicrobial activity (in-vivo) and found that the compounds 12, 13 and 14 exhibited comparable or higher antibacterial activity then ciprofloxacin (standard) against E. coli, S. enteritidis, P. aeruginosa, S. aureus and B. subtilis. The compounds of series-2 showed significant activity as compared with ciprofloxacin. These compounds could be lead to the selection and use as efficient antimicrobial agents, especially for the treatment of multi-drug resistant infections.

Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1

PubMed Central

Csiszar, Anna; Labinskyy, Nazar; Jimenez, Rosario; Pinto, John T.; Ballabh, Praveen; Losonczy, Gyorgy; Pearson, Kevin J.; de Cabo, Rafael; Ungvari, Zoltan

2009-01-01

Endothelial-dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular-disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholine-induced relaxation, vascular oxidative stress and increased NF-κB-activity. Lifelong CR significantly improved endothelial function, attenuated vascular ROS production, inhibited NF-κB activity and down-regulated inflammatory genes. To elucidate the role of circulating factors in mediation of the vasoprotective effects of CR, we determined whether sera obtained from CR-animals can confer anti-oxidant and anti-inflammatory effects in cultured coronary-arterial endothelial cells (CAECs), mimicking the effects of CR. In CAECs cultured in the presence of AL-serum TNFα elicited oxidative-stress, NF-κB-activation and inflammatory gene expression. By contrast, treatment of CAECs with CR-serum attenuated TNFα-induced ROS generation and prevented NF-κB-activation and induction of inflammatory genes. siRNA-knockdown of SIRT1 mitigated the anti-oxidant and anti-inflammatory effects of CR-serum. CR exerts anti-oxidant and anti-inflammatory vascular effects, which are likely mediated by circulating factors, in part, via a SIRT1-dependent pathway. PMID:19549533

Brazilian medicinal plants with corroborated anti-inflammatory activities: a review.

PubMed

Ribeiro, Victor Pena; Arruda, Caroline; Abd El-Salam, Mohamed; Bastos, Jairo Kenupp

2018-12-01

Inflammatory disorders are common in modern life, and medicinal plants provide an interesting source for new compounds bearing anti-inflammatory properties. In this regard, Brazilian medicinal plants are considered to be a promising supply of such compounds due to their great biodiversity. To undertake a review on Brazilian medicinal plants with corroborated anti-inflammatory activities by selecting data from the literature reporting the efficacy of plants used in folk medicine as anti-inflammatory, including the mechanisms of action of their extracts and isolated compounds. A search in the literature was undertaken by using the following Web tools: Web of Science, SciFinder, Pub-Med and Science Direct. The terms 'anti-inflammatory' and 'Brazilian medicinal plants' were used as keywords in search engine. Tropicos and Reflora websites were used to verify the origin of the plants, and only the native plants of Brazil were included in this review. The publications reporting the use of well-accepted scientific protocols to corroborate the anti-inflammatory activities of Brazilian medicinal plants with anti-inflammatory potential were considered. We selected 70 Brazilian medicinal plants with anti-inflammatory activity. The plants were grouped according to their anti-inflammatory mechanisms of action. The main mechanisms involved inflammatory mediators, such as interleukins (ILs), nuclear factor kappa B (NF-κB), prostaglandin E2 (PGE2), cyclooxygenase (COX) and reactive oxygen species (ROS). The collected data on Brazilian medicinal plants, in the form of crude extract and/or isolated compounds, showed significant anti-inflammatory activities involving different mechanisms of action, indicating Brazilian plants as an important source of anti-inflammatory compounds.

Anti-inflammatory and antioxidant activities of extracts from Musa sapientum peel.

PubMed

Phuaklee, Pathompong; Ruangnoo, Srisopa; Itharat, Arunporn

2012-01-01

Many parts of Musa sapientum Linn. (Musaceae) are used in Thai traditional medicine as drugs, food supplements and cosmetics. The banana peel is used as an astringent in foot care, the unripe fruit is used to treat diarrhea and, the ripe fruit is used as tonic. To evaluate anti-inflammatory and antioxidant activities of banana peel extracts obtained from different extraction methods and to determine their total phenolic content. Four extraction methods were used to extract unripe and ripe peels. Nitric oxide inhibitory and DPPH scavenging assays were used to evaluate anti-inflammatory and antioxidant activities, respectively. Folin-Ciocalteu's reagent was used to determine total phenolic content. The water extract of fresh ripe peel exhibited the most potent NO inhibitory activity (IC50 = 6.68 +/- 0.34 microg/ml), but apparently exhibited no antioxidant activity. The decoction extract of fresh unripe peel exhibited strong antioxidant activity as well as had the highest total phenolic compound. The antioxidant activity exhibited a correlation with the total phenolic content. This study supports the use of Musa sapientum peel in Thai Traditional Medicine for treatment of inflammatory-related diseases.

Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages

PubMed Central

Ko, Wan-Kyu; Lee, Soo-Hong; Kim, Sung Jun; Jo, Min-Jae; Kumar, Hemant; Han, In-Bo; Sohn, Seil

2017-01-01

Purpose The aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods We induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO). Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in mitogen-activated protein kinase (MAPK) signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) signaling pathways were evaluated by western blot assays. Results UDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-α (IL-1α), interleukin 1-β (IL-1β), and interleukin 6 (IL-6) in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10) in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB) in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA. Conclusion UDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug. PMID:28665991

Anti-inflammatory activities of essential oil isolated from the calyx of Hibiscus sabdariffa L.

PubMed

Shen, Chun-Yan; Zhang, Tian-Tian; Zhang, Wen-Li; Jiang, Jian-Guo

2016-10-12

Hibiscus sabdariffa Linn., belonging to the family of Malvaceae, is considered to be a plant with health care applications in China. The main purpose of this study was to analyze the composition of its essential oil and assess its potential therapeutic effect on anti-inflammatory activity. A water steam distillation method was used to extract the essential oil from H. Sabdariffa. The essential oil components were determined by gas chromatography/mass spectrometry (GC-MS) analysis and a total of 18 volatile constituents were identified, the majority of which were fatty acids and ester compounds. Biological activity showed that the essential oil extracted from H. Sabdariffa exhibited excellent anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. The nitric oxide (NO) inhibition rate reached 67.46% when the concentration of the essential oil was 200 μg mL -1 . Further analysis showed that the anti-inflammatory activity of the essential oil extracted from H. Sabdariffa might be exerted through inhibiting the activation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways to decrease NO and pro-inflammatory cytokine (IL-1, IL-6, TNF-α, COX-2, and iNOS) production. Thus, the essential oil extracted from H. Sabdariffa is a good source of a natural product with a beneficial effect against inflammation, and it may be applied as a food supplement and/or functional ingredient.

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.

Analgesic and anti-inflammatory activities of Piper nigrum L.

PubMed

Tasleem, Farhana; Azhar, Iqbal; Ali, Syed Nawazish; Perveen, Shaista; Mahmood, Zafar Alam

2014-09-01

To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

PubMed

Dasgupta, Queeny; Movva, Sahitya; Chatterjee, Kaushik; Madras, Giridhar

2017-08-07

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h -0.61 . The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis of modified steroids as a novel class of non-ulcerogenic, anti-inflammatory and anti-nociceptive agents.

PubMed

Mohareb, Rafat M; Elmegeed, Gamal A; Abdel-Salam, Omar M E; Doss, Senot H; William, Marian G

2011-01-01

The identification of compounds able to treat both pain and inflammation with limited side effects is one of the prominent goals in biomedical research. This study aimed at the synthesis of new modified steroids with structures justifying non-ulcerogenic, anti-inflammatory and anti-nociceptive activities. The steroid derivatives were synthesized via straightforward and efficient methods and their structures were established based on the analytical and spectral data. The in vivo anti-inflammatory, anti-nociceptive and anti-ulcerogenic activities of some of these compounds were studied. The newly synthesized compounds 8b, 19b, 24 and 31a showed anti-inflammatory, anti-nociceptive and anti-ulcerogenic activity with various intensities. Oedema was significantly reduced by either dose 25 or 50 mg/kg of all tested compounds at 3 and 4 h post-carrageenan. Compound 19b was the most effective in alleviating thermal pain. The analgesic activity of either dose of the compounds 8b, 24, 31a as well as the high dose 19b was significantly higher than that for indomethacin (IND). Gastric mucosal lesions caused in the rats by the administration of 96% EtOH and IND were inhibited by all tested compounds administered at (50 mg/kg) dose in the study. Copyright © 2011 Elsevier Inc. All rights reserved.

Anti-inflammatory agents from Sandoricum koetjape Merr.

PubMed

Rasadah, M A; Khozirah, S; Aznie, A A; Nik, M M

2004-02-01

The anti-inflammatory activity of the stem extracts of Sandoricum koetjape was investigated on topical administration using the TPA (tetradecanoylphorbol acetate)-induced mouse ear inflammation model. Bioassay-guided chromatographic fractionation of active fractions led to the isolation 3-oxo-12-oleanen-29-oic acid and katonic acid as the bioactive principles responsible for the anti-inflammatory acitivity. The percentage of inhibition exhibited by 3-oxo-12-oleanen-29-oic acid was almost equivalent to indomethacin.

In vitro anti-inflammatory and anti-cancer activities of Cuscuta reflexa Roxb.

PubMed

Suresh, V; Sruthi, V; Padmaja, B; Asha, V V

2011-04-12

To determine anti-inflammatory and anti-cancer activities of Cuscuta reflexa in cell lines (in vitro). Anti-inflammatory activity of the water extract was analysed in vitro using lipopolysaccharide (LPS) induced inflammatory reactions in murine macrophage cell line RAW264.7. The expression of COX-2 and TNF-α genes involved in inflammation was analysed by SQ RT-PCR. EMSA was conducted to analyse the influence of the extract on NF-κB signalling. Anti-cancer activity was analysed on Hep3B cells by MTT assay, DAPI staining, annexin V staining and SQ-RT PCR analysis of BAX, Bcl-2, p53 and survivin. The extract down regulated LPS induced over expression of TNF-α and COX-2 in RAW264.7 cells; blocked NF-κB binding to its motifs and induced apoptosis in Hep3B cells as evidenced from MTT, DAPI staining and annexin V staining assays. The extract up regulated pro-apoptotic factors BAX and p53, and down regulated anti-apoptotic factors Bcl-2 and survivin. The study showed that Cuscuta reflexa inhibits LPS induced inflammatory responses in RAW264.7 cells through interplay of TNF-α, COX-2 and NF-κB signalling. It induced apoptosis in Hep3B cells through the up regulation of p53, BAX and down regulation of Bcl-2 and survivin. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Polyphenols isolated from Acacia mearnsii bark with anti-inflammatory and carbolytic enzyme inhibitory activities.

PubMed

Xiong, Jia; Grace, Mary H; Esposito, Debora; Komarnytsky, Slavko; Wang, Fei; Lila, Mary Ann

2017-11-01

The present study was designed to characterize the polyphenols isolated from Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high-speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory and carbolytic enzymes (α-glucosidase and α-amylase) inhibitory activities. Fractions B4, B5, B6, B7 (total phenolics 850.3, 983.0, 843.9, and 572.5 mg·g -1 , respectively; proanthocyanidins 75.7, 90.5, 95.0, and 44.8 mg·g -1 , respectively) showed significant activities against reactive oxygen species (ROS), nitric oxide (NO) production, and expression of pro-inflammatory genes interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7. All the extracts suppressed α-glucosidase and α-amylase activities, two primary enzymes responsible for carbohydrate digestion. A. mearnsii bark samples possessed significantly stronger inhibitory effects against α-glucosidase enzyme (IC 50 of 0.4-1.4 μg·mL -1 ) than the pharmaceutical acarbose (IC 50 141.8 μg·mL -1 ). B6 and B7 (IC 50 17.6 and 11.7 μg·mL -1 , respectively) exhibited α-amylase inhibitory activity as efficacious as acarbose (IC 50 15.4 μg·mL -1 ). Moreover, B extract, at 25 µg·mL -1 , significantly decreased the non-mitochondrial oxidative burst that is often associated with inflammatory response in human monocytic macrophages. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Enhancement of the anti-inflammatory activity of temporin-1Tl-derived antimicrobial peptides by tryptophan, arginine and lysine substitutions.

PubMed

Rajasekaran, Ganesan; Kamalakannan, Radhakrishnan; Shin, Song Yub

2015-10-01

Temporin-1Tl (TL) is a 13-residue frog antimicrobial peptide (AMP) exhibiting potent antimicrobial and anti-inflammatory activity. To develop novel AMP with improved anti-inflammatory activity and antimicrobial selectivity, we designed and synthesized a series of TL analogs by substituting Trp, Arg and Lys at selected positions. Except for Escherichia coli and Staphylococcus epidermidis, all TL analogs exhibited retained or increased antimicrobial activity against seven bacterial strains including three methicillin-resistant Staphylococcus aureus strains compared with TL. TL-1 and TL-4 showed a little increase in antimicrobial selectivity, while TL-2 and TL-3 displayed slightly decreased antimicrobial selectivity because of their about twofold increased hemolytic activity. All TL analogs demonstrated greatly increased anti-inflammatory activity, evident by their higher inhibition of the production tumor necrosis factor-α (TNF-α) and nitric oxide and the mRNA expression of inducible nitric oxide synthase and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti-inflammatory activity is as follows: TL-2 ≈ TL-3 ≈ TL-4 > TL-1 > TL. In addition, LPS binding ability of the peptides corresponded with their anti-inflammatory activity. These results apparently suggest that the anti-inflammatory activity of TL analogs is associated with the direct binding ability between these peptides and LPS. Collectively, our designed TL analogs possess improved anti-inflammatory activity and retain antimicrobial activity without a significant increase in hemolysis. Therefore, it is evident that our TL analogs constitute promising candidates for the development of peptide therapeutics for gram-negative bacterial infection. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

6-Shogaol ameliorates diabetic nephropathy through anti-inflammatory, hyperlipidemic, anti-oxidative activity in db/db mice.

PubMed

Xu, Yun; Bai, Liwei; Chen, Xuehui; Li, Yan; Qin, Yan; Meng, Xiangyu; Zhang, Qinggui

2018-01-01

The prevalence of type 2 diabetes mellitus has been increasing worldwide and more than two thirds of the patients may develop diabetic nephropathy (DN). However, the efficiency of existing approaches on DN progression is limited. 6-Shogaol (6-SG), a major dehydrated derivative of gingerols, possesses various biological properties. The present study was designed to evaluate the possible effects of 6-SG on DN in db/db mice and to investigate the mechanisms. We revealed that 6-SG reduced the levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure. 6-SG decreased the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological injuries of kidneys, reduced the surface area of Bowman's capsule, Bowman's space, glomerular tuft, and decreased the expression of collagen IV and fibronectin in kidneys of db/db mice. The high levels of systemic and renal triglyceride and cholesterol were decreased by 6-SG. Moreover, 6-SG exhibited anti-inflammatory effects, as reflected by reduction of tumor necrosis factor ɑ (TNFɑ), monocyte chemotactic protein-1 (MCP-1), and IL-6 levels in circulation and kidneys, and decrease of NF-κB expression. Furthermore, 6-SG also inhibited oxidative stress and restored the expression of NF-E2-related factor 2 (Nrf2) in kidneys of db/db mice. In conclusion, we have demonstrated that 6-SG exhibits anti-diabetic and renal protective effects against DN, in which effect the anti-inflammatory, hyperlipidemic, anti-oxidative activities may be involved. Overall, 6-SG could be a promising therapeutic treatment to ameliorate diabetes and the development of DN. Copyright © 2017. Published by Elsevier Masson SAS.

Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide

PubMed Central

Jayakumar, Thanasekaran; Hsieh, Cheng-Ying; Lee, Jie-Jen; Sheu, Joen-Rong

2013-01-01

Andrographis paniculata (Burm. F) Nees, generally known as “king of bitters,” is an herbaceous plant in the family Acanthaceae. In China, India, Thailand, and Malaysia, this plant has been widely used for treating sore throat, flu, and upper respiratory tract infections. Andrographolide, a major bioactive chemical constituent of the plant, has shown anticancer potential in various investigations. Andrographolide and its derivatives have anti-inflammatory effects in experimental models asthma, stroke, and arthritis. In recent years, pharmaceutical chemists have synthesized numerous andrographolide derivatives, which exhibit essential pharmacological activities such as those that are anti-inflammatory, antibacterial, antitumor, antidiabetic, anti-HIV, antifeedant, and antiviral. However, what is noteworthy about this paper is summarizing the effects of andrographolide against cardiovascular disease, platelet activation, infertility, and NF-κB activation. Therefore, this paper is intended to provide evidence reported in relevant literature on qualitative research to assist scientists in isolating and characterizing bioactive compounds. PMID:23634174

Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods.

PubMed

Gunawardena, Dhanushka; Shanmugam, Kirubakaran; Low, Mitchell; Bennett, Louise; Govindaraghavan, Suresh; Head, Richard; Ooi, Lezanne; Münch, Gerald

2014-02-01

Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. In search of anti-inflammatory foods, we have systematically screened a variety of common dietary plants and mushrooms for their anti-inflammatory activity. A selection of 115 samples was prepared by a generic food-compatible processing method involving heating. These products were tested for their anti-inflammatory activity in murine N11 microglia and RAW 264.7 macrophages, using nitric oxide (NO) and tumour necrosis factor-α (TNF-α) as pro-inflammatory readouts. Ten food samples including lime zest, English breakfast tea, honey-brown mushroom, button mushroom, oyster mushroom, cinnamon and cloves inhibited NO production in N11 microglia, with IC50 values below 0.5 mg/ml. The most active samples were onion, oregano and red sweet potato, exhibiting IC50 values below 0.1 mg/ml. When these ten food preparations were retested in RAW 264.7 macrophages, they all inhibited NO production similar to the results obtained in N11 microglia. In addition, English breakfast tea leaves, oyster mushroom, onion, cinnamon and button mushroom preparations suppressed TNF-α production, exhibiting IC50 values below 0.5 mg/ml in RAW 264.7 macrophages. In summary, anti-inflammatory activity in these food samples survived 'cooking'. Provided that individual bioavailability allows active compounds to reach therapeutic levels in target tissues, these foods may be useful in limiting inflammation in a variety of age-related inflammatory diseases. Furthermore, these foods could be a source for the discovery of novel anti-inflammatory drugs.

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential*

PubMed Central

Bloom, Joshua; Metz, Christine; Nalawade, Saisha; Casabar, Julian; Cheng, Kai Fan; He, Mingzhu; Sherry, Barbara; Coleman, Thomas; Forsthuber, Thomas; Al-Abed, Yousef

2016-01-01

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in a broad range of inflammatory and oncologic diseases. MIF is unique among cytokines in terms of its release profile and inflammatory role, notably as an endogenous counter-regulator of the anti-inflammatory effects of glucocorticoids. In addition, it exhibits a catalytic tautomerase activity amenable to the design of high affinity small molecule inhibitors. Although several classes of these compounds have been identified, biologic characterization of these molecules remains a topic of active investigation. In this study, we used in vitro LPS-driven assays to characterize representative molecules from several classes of MIF inhibitors. We determined that MIF inhibitors exhibit distinct profiles of anti-inflammatory activity, especially with regard to TNFα. We further investigated a molecule with relatively low anti-inflammatory activity, compound T-614 (also known as the anti-rheumatic drug iguratimod), and found that, in addition to exhibiting selective MIF inhibition in vitro and in vivo, iguratimod also has additive effects with glucocorticoids. Furthermore, we found that iguratimod synergizes with glucocorticoids in attenuating experimental autoimmune encephalitis, a model of multiple sclerosis. Our work identifies iguratimod as a valuable new candidate for drug repurposing to MIF-relevant diseases, including multiple sclerosis. PMID:27793992

Anti-inflammatory, cyclooxygenase inhibitory and antioxidant activities of standardized extracts of Tridax procumbens L.

PubMed

Jachak, Sanjay M; Gautam, Raju; Selvam, C; Madhan, Himanshu; Srivastava, Amit; Khan, Taj

2011-03-01

The standardized EtOAc, MeOH and 70% EtOH extracts of Tridax procumbens aerial parts showed significant inhibition of rat paw edema at a medium dose of 200mg/kg and the EtOAC extract was the most active. These extracts were standardized by HPLC with the help of chemical markers. Further, the extracts were evaluated for COX-1 and COX-2 inhibitory activity and EtOAc extract exhibited the highest inhibition of COX-1 and COX-2 at 50 μg/mL. Cent aurein, centaureidin and bergenin were isolated as COX-1 and COX-2 inhibitory principles from the EtOAc extract. The extracts also exhibited antioxidant activity against DPPH and ABTS free radicals. The anti-inflammatory activity of T. procumbens aerial parts could be at least in part due to COX-1, COX-2 enzyme inhibition and free radical-scavenging activities which may be attributed to the presence of flavonoids and other polyphenols in the extracts. Copyright © 2010 Elsevier B.V. All rights reserved.

RETRACTED: Sophocarpine displays anti-inflammatory effect via inhibiting TLR4 and TLR4 downstream pathways on LPS-induced mastitis in the mammary gland of mice.

PubMed

Wang, Dehai; Xu, Niannian; Zhang, Zhenbiao; Yang, Shijin; Qiu, Changwei; Li, Chengye; Deng, Ganzhen; Guo, Mengyao

2016-06-01

Mastitis is defined as the inflammation of the mammary gland. LPS, which is widely used to induce mastitis models for the study of this disease, triggers similar inflammation as Escherichia coli. Sophocarpine, isolated from Sophora alopecuroides L., exhibits multiple biological properties. The aim of the present study was to determine the anti-inflammatory effect and mechanism of action of sophocarpine on mastitis within an LPS-induced mouse model. ELISA and western blotting were performed to detect protein levels. The qPCR was performed to detect mRNA levels. The ELISA and qRT-PCR results showed that sophocarpine inhibited the expression of TNF-α, IL-1β and IL-6 in a dose-dependent manner. However, sophocarpine suppressed TLR4 expression. Further study showed that sophocarpine could suppress the phosphorylation of IκBα, p65 and p38. These results confirm that sophocarpine played an anti-inflammatory role in LPS-induced mastitis by regulating TLR4 and the NF-κB and MAPK signaling pathways in mammary gland tissues. Therefore, sophocarpine may be a potential therapeutic drug for the treatment of mastitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of Psidium guineense Sw. and spathulenol.

PubMed

do Nascimento, Kamilla Felipe; Moreira, Flora Martinez Figueira; Alencar Santos, Joyce; Kassuya, Candida Aparecida Leite; Croda, Julio Henrique Rosa; Cardoso, Claudia Andrea Lima; Vieira, Maria do Carmo; Góis Ruiz, Ana Lúcia Tasca; Ann Foglio, Mary; de Carvalho, João Ernesto; Formagio, Anelise Samara Nazari

2018-01-10

Leaves from Psidium guineense Sw. are used in popular medicine for the treatment of inflammatory disease. However, there is no scientific evidence demonstrating this activity. To evaluate the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of P. guineense and spathulenol (a major constituent). The study was conducted in part to provide evidence supporting the ethnobotanical use of the leaves of this species. The essential oil (EOPG) was extracted from the leaves of P. guineense by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). The major compound, spathulenol (PG-1), was isolated in a chromatographic column and characterized by nuclear magnetic resonance (NMR). EOPG and PG-1 were evaluated in vitro for antioxidant activity by DPPH, ABTS and MDA methods; anti-inflammatory potential was assessed using two models, including pleurisy and oedema, in mice. The impact of EOPG and PG-1 on cell proliferation was determined via spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay, and anti-Mycobacterium tuberculosis activity was determined using the REMA method. A total of 38 components were identified from the EOPG, with the sesquiterpenic alcohol spathulenol (PG-1) (80.7%) being the major constituent. EOPG and PG-1 exhibited the highest antioxidant activities in the DPPH and MDA system compared with reference standard, with IC 50 values ranging from 26.13 to 85.60μg/mL. Oral administration of EOPG and PG-1 showed significant inhibition in the Cg-induced mice paw oedema and pleurisy model. The EOPG (GI 50 = 0.89μg/mL) and PG-1 (GI 50 = 49.30μg/mL) were particularly effective against the ovarian cancer cell line. Both showed moderate antimycobacterial activity. For the first time, this study demonstrated the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial properties of the essential oil of P. guineense (leaves were collected in Dourados-MS) and spathulenol, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect. Copyright © 2017. Published by Elsevier B.V.

Synthesis, pharmacological activities and molecular docking studies of pyrazolyltriazoles as anti-bacterial and anti-inflammatory agents.

PubMed

Dayakar, Cherupally; Kumar, Buddana Sudheer; Sneha, Galande; Sagarika, Gudem; Meghana, Koneru; Ramakrishna, Sistla; Prakasham, Reddy Shetty; China Raju, Bhimapaka

2017-10-15

A series of novel pyrazolyl alcohols (5a-h), pyrazolyl azides (6a-h), and pyrazolyltriazoles (8a-h, 10a-p and 12a-l) were prepared and evaluated for their bioactivity (anti-bacterial and anti-inflammatory) profile. The compound 5c displayed the potent anti-bacterial activity against Micrococcus luteus (MIC 3.9 and MBC 7.81µg/mL). In vitro anti-inflammatory activity data denoted that compound 8b is effective among the tested compounds against IL-6 (IC 50 6.23μM). Docking analysis of compounds 5f, 8a-b, 8e-f and 8h displayed high binding energies for the compounds 8a-b and 8h towards TNF-α dimer (2AZ5 protein) and IL-6 (1ALU protein). In vivo anti-inflammatory activity of compounds 8b and 8h with respect to LPS induced mice model indicated that compound 8h showed significant reduction in TNF-α. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discovery of Novel Small-molecule Inhibitors of Nuclear Factor-κB Signaling with Anti-inflammatory and Anti-cancer Properties.

PubMed

Zhang, Lei; Shi, Lei; Soars, Shafer; Kamps, Joshua; Yin, Hang Hubert

2018-06-05

Excessive NF-κB activation contributes to the pathogenesis of numerous diseases. Small-molecule inhibitors of NF-κB signaling have significant therapeutic potential especially in treating inflammatory diseases and cancers. In this study, we performed a cell-based high-throughput screening to discover novel agents capable of inhibiting NF-κB signaling. Based on two hit scaffolds from the screening, we synthesized 69 derivatives to optimize the potency for inhibition of NF-κB activation, leading to successful discovery of the most potent compound Z9j with over 170-fold enhancement of inhibitory activity. Preliminary mechanistic studies revealed that Z9j inhibited NF-κB signaling via suppression of Src/Syk, PI3K/Akt and IKK/IκB pathways. This novel compound also demonstrated anti-inflammatory and anti-cancer activities, warranting its further development as a potential multifunctional agent to treat inflammatory diseases and cancers.

Geraniol ameliorates TNBS-induced colitis: Involvement of Wnt/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways.

PubMed

Soubh, Ayman A; Abdallah, Dalaal M; El-Abhar, Hanan S

2015-09-01

Geraniol, a natural component of plant essential oils, exhibits potent chemopreventive effects in the colon; however, its possible role/mechanisms in experimental colitis have not been elucidated, which is the aim of this study. To fulfill this goal, rats were treated for 11days with geraniol and/or sulfasalazine using a TNBS-induced colitis model. Geraniol significantly hindered the colitis-clinical signs (weight loss, colon edema,ulcerative area, colon/spleen mass indices) and opposed the altered oxidative/nitrosative stress. It restored the depleted total antioxidant capacity and lessened the elevated levels of nitric oxide and lipid peroxide. TNBS induced apoptosis and inflammatory cell infiltration, whereas geraniol curtailed these effects by diminishing the levels of caspase-3, intercellular adhesion molecule-1, and myeloperoxidase. The anti-inflammatory effect was documented by inhibiting the colon contents of prostaglandin E2 and interleukin-1β. In order to delve into the anti-colitic signaling pathways, geraniol inhibited the content/expression of glycogen synthase kinase (GSK)-3β, β-catenin, p38 mitogen activated protein kinase (p38MAPK), and nuclear factor kappa B (NFκB), but upregulated that of peroxisome proliferator activated receptor γ (PPARγ). These effects were comparable to those of sulfasalazine, the standard drug, whereas its combination with geraniol mediated effects that surpassed either treatment alone. Geraniol in the current study improved experimental colitis partly via its antioxidant, anti-inflammatory, and immunosuppressive potentials, possibly by modulating the Wnt/GSK-3β/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways. The study also revealed that geraniol represents a valuable asset against colitis alone or in combination with the conventional anti-colitic therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

Peptic ulcer frequency differences related to h. Pylori or aines.

PubMed

Carli, Diego Michelon de; Pires, Rafael Cardoso; Rohde, Sofia Laura; Kavalco, Caroline Mayara; Fagundes, Renato Borges

2015-01-01

Peptic ulcer etiology has been changing because of H. pylori decline. To estimate peptic ulcer prevalence in 10 years-interval and compare the association with H. pylori and use of non-steroidal anti-inflammatory drugs. Methods Records assessment in two periods: A (1997-2000) and B (2007-2010), searching for peptic ulcer, H. pylori infection and non-steroidal anti-inflammatory drugs use. Peptic ulcer occurred in 30.35% in A and in 20.19% in B. H. pylori infection occurred in 73.3% cases in A and in 46.4% in B. Non-steroidal anti-inflammatory drugs use was 3.5% in A and 13.3% in B. Neither condition occurred in 10.4% and 20.5% in A and B respectively. Comparing both periods, we observed reduction of peptic ulcer associated to H. pylori (P=0.000), increase of peptic ulcer related to non-steroidal anti-inflammatory drugs (P=0.000) and idiopathic peptic ulcer (P=0.002). The concurrent association of H. pylori and non-steroidal anti-inflammatory drugs was also higher in B (P=0.002). Rates of gastric ulcer were higher and duodenal ulcer lower in the second period. After 10 years, the prevalence of peptic ulcer decreased, as well as ulcers related to H. pylori whereas ulcers associated to non-steroidal anti-inflammatory drugs increased. There was an inversion in the pattern of gastric and duodenal ulcer and a rise of idiopathic peptic ulcer.

Antinociceptive and anti-inflammatory activities of standardized extract of polymethoxyflavones from Ageratum conyzoides.

PubMed

Faqueti, Larissa G; Brieudes, Vincent; Halabalaki, Maria; Skaltsounis, Alexios L; Nascimento, Leandro F; Barros, Wellinghton M; Santos, Adair R S; Biavatti, Maique W

2016-12-24

Ageratum conyzoides L. is a plant widely used in traditional medicine in tropical and subtropical regions of the world due to its anti-inflammatory, antinociceptive and antibacterial properties. To characterize the standardized extract of polymethoxyflavones (SEPAc) from the plant and evaluate its antinociceptive and anti-inflammatory effects. The SEPAc purified from the ethanol extract of the plant leaves was characterized by high resolution mass spectrometry and the methoxyflavones were quantified by a validated UPLC-PDA method. The antinociceptive and anti-inflammatory activities of the SEPAc were evaluated after oral administration on the acute nocifensive behavior of mice induced by formalin, prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukin-1beta (IL-1β)) and tumor necrosis factor-alpha (TNF-α) in mice. Qualitative analyses revealed the presence of seven methoxyflavones in the SEPAc, also a simple UPLC-PDA method was developed and validated for the quantification of 5,6,7,3',4',5'-hexametoxyflavone; nobiletin; 5'-methoxynobiletin and eupalestin, major compounds in the extract. The SEPAc exhibited antinociceptive and anti-inflammatory activities in both formalin phases, with significant inhibition of the paw edema formation and significant reduction of the nocifensive response induced by an intraplantar injection of PGE2 and intrathecal injection of interleukin-1β. The SEPAc exhibited significant antinociceptive and anti-inflammatory effects. These results provided scientific suggestion of its potential as a source of new medicines to treat inflammatory diseases, such rheumatoid arthritis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Differential Action between Schisandrin A and Schisandrin B in Eliciting an Anti-Inflammatory Action: The Depletion of Reduced Glutathione and the Induction of an Antioxidant Response

PubMed Central

Leong, Pou Kuan; Wong, Hoi Shan; Chen, Jihang; Chan, Wing Man; Leung, Hoi Yan; Ko, Kam Ming

2016-01-01

Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-κB signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GST/ depleting cellular GSH and inducing an antioxidant response involved in their anti-inflammatory actions. PMID:27195753

Green synthesis, biological and spectroscopic study on the interaction of multi-component Mannich bases of imidazo[2,1-b]benzothiazoles with human serum albumin.

PubMed

Maddili, Swetha K; Yandrati, Leela Prasad; Siddam, Shakuntala; Kannekanti, Vijaya Kumar; Gandham, Himabindu

2017-11-01

A series of Mannich bases of imidazo[2, l-b]benzothiazoles were prepared through one-pot multi-component reaction in the presence of water as an eco-friendly solvent. All the synthesized compounds were confirmed from IR, 1 HNMR, 13 CNMR, and Mass spectroscopy. Evaluation of in vitro anti-inflammatory and anti-microbial activities of all the synthesized derivatives was further accomplished. These results clearly displayed that compound 6d exhibited outstanding anti-inflammatory activity with a percentage inhibition of 70.23% by membrane stabilization method whereas 67.54% at 100μgmL -1 by the albumin denaturation method, which is comparable to the standard Diclofenac. Further screening against five fungal species (C. albicans ATCC 76615, C. mycoderma, C. utilis, A. flavus, and B. yeast) along with four gram positive (Methicillin-resistant S. aureus N315 (MRSA), Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 21216, and Micrococcus luteus ATCC 4698), and six Gram-negative bacterial strains (Escherichia coli DH52, Escherichia coli JM109, Salmonella dysenteriae, Pseudomonas aeruginosa ATCC 27853, Bacillus proteus ATCC13315 and Bacillus typhi) was carried out. These findings manifested that compound 7c displayed excellent antifungal efficacy while compound 7b revealed significant anti-microbial activity. In addition binding behaviour of compound 7b was investigated by binding study between calf thymus DNA and compound 7b by UV-Vis absorption spectroscopy and further research about HSA interactions was carried out. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical composition, antioxidative and anti-inflammatory activity of extracts prepared from aerial parts of Oenothera biennis L. and Oenothera paradoxa Hudziok obtained after seeds cultivation.

PubMed

Granica, Sebastian; Czerwińska, Monika E; Piwowarski, Jakub P; Ziaja, Maria; Kiss, Anna K

2013-01-30

In the present study we investigated the chemical composition of extracts prepared from aerial parts of Oenothera paradoxa Hudziok and Oenothera biennis L. and their antioxidative and anti-inflammatory activities. Ultra high pressure liquid chromatography (UHPLC)-DAD-MS/MS studies showed that both extracts contain a wide variety of polyphenols (39 identified constituents) among which macrocyclic ellagitannin turned out to be the main constituent. During the in vitro studies, using noncellular models, both extracts scavenged reactive oxygen species (ROS) in a concentration-dependent manner, and the lowest SC(50) values were obtained for O(2)(-) and H(2)O(2). Both extracts inhibited ROS production by stimulated human neutrophils. The stronger activity in the case of formyl-met-leu-phenylalanine stimulation suggests that both extracts may act through the receptor-dependent pathway. O. paradoxa extract and O. biennis extract exhibited anti-inflammatory activity by the inhibition of hyaluronidase and lipoxygenase in a concentration-dependent manner. The stronger activity of O.biennis extract toward lipoxygenase may be explained by its higher oenothein B content.

Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents.

PubMed

Gautam, Raju; Jachak, Sanjay M; Kumar, Vivek; Mohan, C Gopi

2011-03-15

Stellatin (4), isolated from Dysophylla stellata is a cyclooxygenase (COX) inhibitor. The present study reports the synthesis and biological evaluation of new stellatin derivatives for COX-1, COX-2 inhibitory and anti-inflammatory activities. Eight derivatives showed more pronounced COX-2 inhibition than stellatin and, 17 and 21 exhibited the highest COX-2 inhibition. They also exhibited the significant anti-inflammatory activity in TPA-induced mouse ear edema assay and their anti-inflammatory effects were more than that of stellatin and indomethacin at 0.5mg/ear. The derivatives were further evaluated for antioxidant activity wherein 16 and 17 showed potent free radical scavenging activity against DPPH and ABTS radicals. Molecular docking study revealed the binding orientations of stellatin and its derivatives into the active sites of COX-1 and COX-2 and thereby helps to design the potent inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Blunted activation of NF-{kappa}B and NF-{kappa}B-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response

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

Hayakawa, Kunihiro; Hiramatsu, Nobuhiko; Okamura, Maro

2008-01-04

Geranylgeranylacetone (GGA), an anti-ulcer agent, has anti-inflammatory potential against experimental colitis and ischemia-induced renal inflammation. However, molecular mechanisms involved in its anti-inflammatory effects are largely unknown. We found that, in glomerular mesangial cells, GGA blocked activation of nuclear factor-{kappa}B and consequent induction of monocyte chemoattractant protein 1 (MCP-1) by inflammatory cytokines. It was inversely correlated with induction of unfolded protein response (UPR) evidenced by expression of 78 kDa glucose-regulated protein (GRP78) and suppression of endoplasmic reticulum stress-responsive alkaline phosphatase. Various inducers of UPR including tunicamycin, thapsigargin, A23187, 2-deoxyglucose, dithiothreitol, and AB{sub 5} subtilase cytotoxin reproduced the suppressive effects of GGA.more » Furthermore, attenuation of UPR by stable transfection with GRP78 diminished the anti-inflammatory effects of GGA. These results disclosed a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of GGA.« less

Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and endotoxemia through an IL-10 STAT3-dependent mechanism.

PubMed

Grant, Louise; Shearer, Kirsty D; Czopek, Alicja; Lees, Emma K; Owen, Carl; Agouni, Abdelali; Workman, James; Martin-Granados, Cristina; Forrester, John V; Wilson, Heather M; Mody, Nimesh; Delibegovic, Mirela

2014-02-01

Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage associated with decreased proinflammatory cytokine secretion in vivo. In vitro, LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in TNF-α mRNA levels. These anti-inflammatory effects were associated with increased LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic inflammation induced by high-fat (HF) feeding led to equally beneficial effects of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and expansion of cells expressing myeloid markers. These increased IL-10 levels negatively correlated with circulating insulin and alanine transferase levels. Our studies implicate myeloid PTP1B in negative regulation of STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential anti-inflammatory and antidiabetic target in obesity.

Synthesis of 4-substituted pyrido[2,3-d]pyrimidin-4(1H)-one as analgesic and anti-inflammatory agents.

PubMed

El-Gazzar, Abdel-Rahman B A; Hafez, Hend N

2009-07-01

4-Substituted-pyrido[2,3-d]pyrimidin-4(1H)-ones 4a-c were synthesized by oxidation of 4-substituted-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones 3a-c which were in turn prepared from arylidenemalononitriles 1a-c and 6-aminothiouracil 2. The reactivity of compounds 4a-c towards some reagents such as formamide, carbon disulfide, urea, thiourea, formic and acetic acids were studied. All the synthesized compounds were characterized by spectroscopic means and elemental analysis. Compound 4c exhibited 64% and 72% analgesic activity. Also, compound 4b showed 50% and 65% anti-inflammatory activity. Interestingly these compounds showed one-third of ulcer index of the reference aspirin and diclofenac.

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 effect of the extracts from the branch of Taxillus yadoriki being parasitic in Neolitsea sericea in LPS-stimulated RAW264.7 cells.

PubMed

Park, Su Bin; Park, Gwang Hun; Kim, Ha Na; Son, Ho-Jun; Song, Hun Min; Kim, Hyun-Seok; Jeong, Hyung Jin; Jeong, Jin Boo

2018-05-11

Mistletoe has been used as the herbal medicine to treat hypertension, diabetes mellitus, inflammation, arthritis and viral infection. In this study, we evaluated the anti-inflammatory effect of extracts of branch from Taxillus yadoriki being parasitic in Neolitsea sericea (TY-NS-B) using in vitro model. TY-NS-B significantly inhibited LPS-induced secretion of NO and PGE 2 in RAW264.7 cells. TY-NS-B was also observed to inhibit LPS-mediated iNOS COX-2 expression. In addition, TY-NS-B attenuated production of inflammatory cytokines such as TNF-α and IL-1β induced by LPS. TY-NS-B blocked LPS-mediated inhibitor of IκB-α, and inhibited p65 translocation to the nucleus and NF-κB activation. Furthermore, TY-NS-B reduced the phosphorylation of MAPKs such as p38 and JNK, but not ERK1/2. In addition, TY-NS-B increased ATF3 expression and ATF3 knockdown by ATF3 siRNA attenuated TY-NS-B-mediated inhibition of pro-inflammatory mediator expression. Collectively, our results suggest that TY-NS-B exerts potential anti-inflammatory effects by suppressing NF-κB and MAPK signaling activation, and increasing ATF3 expression. These findings indicate that TY-NS-B could be further developed as an anti-inflammatory drug. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium.

PubMed

Lin, Wang-Ching; Deng, Jeng-Shyan; Huang, Shyh-Shyun; Wu, Sheng-Hua; Chen, Chin-Chu; Lin, Wan-Rong; Lin, Hui-Yi; Huang, Guan-Jhong

2017-02-07

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit myeloperoxidase (MPO) activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit high mobility group box-1 protein 1 (HNGB1) activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes Heme oxygenase 1 (HO-1) and Thioredoxin-1 (Trx-1) in the lung tissue and regulate signal transduction in the KRAB-associated protein-1 (KAP1)/nuclear factor erythroid-2-related factor Nrf2/Kelch Like ECH associated Protein 1 (Keap1) pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced ALI in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases.

Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis.

PubMed

Yu, Tao; Rhee, Man Hee; Lee, Jongsung; Kim, Seung Hyung; Yang, Yanyan; Kim, Han Gyung; Kim, Yong; Kim, Chaekyun; Kwak, Yi-Seong; Kim, Jong-Hoon; Cho, Jae Youl

2016-01-01

Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng's various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.

Anti-nociceptive effect of dexmedetomidine in a rat model of monoarthritis via suppression of the TLR4/NF-κB p65 pathway

PubMed Central

Ji, Dong; Zhou, Yalan; Li, Shuangshuang; Li, Dai; Chen, Hui; Xiong, Yuanchang; Zhang, Yuqiu; Xu, Hua

2017-01-01

As a therapeutic target for neuropathic pain, the anti-nociceptive effects of α 2-adrenoceptors (α2AR) have attracted attention. Dexmedetomidine (DEX), a potent and highly selective α2AR agonist, has exhibited significant analgesic effects in neuropathic pain, but the underlying mechanism has remained elusive. The present study investigated the effect of DEX on Toll-like receptor (TLR)4 and nuclear factor (NF)-κB p65 expression, as well as the production of pro-inflammatory cytokines. The rat monoarthritis (MA) model was induced by intra-articular injection of complete Freund's adjuvant (CFA) at the ankle joint. After induction of MA, the rats were intrathecally treated with normal saline or DEX (2.5 µg) for 3 consecutive days. The concentration of interleukin-1β and −6 as well as tumor necrosis factor-α was examined by ELISA. The expression levels of TLR4 and NF-κB p65 were determined by western blot analysis and immunohistochemistry. The results indicated that the pro-inflammatory cytokines TLR4 and NF-κB p65 were significantly upregulated in MA rats. DEX treatment markedly reduced mechanical and thermal hyperalgesia, suppressed MA-induced elevation of the pro-inflammatory cytokines and inhibited the TLR4/NF-κB p65 pathway, while these effects were blocked by pre-treatment with the selective α2AR antagonist BRL44408 (15 µg) at 30 min prior to CFA injection. These results suggested that DEX has an anti-nociceptive effect via suppressing the TLR4/NF-κB p65 pathway. PMID:29201195

Friedelane-type triterpenoids as selective anti-inflammatory agents by regulation of differential signaling pathways in LPS-stimulated macrophages

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

Villar-Lorenzo, Andrea, E-mail: avillar@iib.uam.es

A series of 31 pentacyclic triterpenoids isolated from the root barks of Celastrus vulcanicola and Maytenus jelskii were tested for cytotoxicity and inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 18 (C18) and 25 (C25) exhibited significant inhibition of LPS-induced NO release at 50 and 25 μM concentrations, respectively, and decreased mRNAs of pro-inflammatory cytokines. At the molecular level, C18 neither inhibited LPS-mediated phosphorylation of mitogen activated protein kinases (MAPKs) nor nuclear translocation of nuclear factor kappa beta (NFκB). Instead, C18 enhanced and prolonged nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) andmore » increased the expression of its target genes including hemeoxigenase 1 (HO1). C25 efficiently inhibited LPS-mediated phosphorylation of JNK, p38 and ERK, without affecting NFκB or Nrf2 signaling pathways. Both compounds reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β (IL1β) proform, reflecting their ability to target the inflammasome. C25 also counteracted LPS effects on iNOS expression and pro-inflammatory cytokines mRNA levels in Bv-2 microglial cells. The anti-inflammatory effect of both compounds was also assessed in human macrophages. Our results suggest that triterpenoids C18 and C25 possess anti-inflammatory effects, which may be therapeutically relevant for diseases linked to inflammation. - Highlights: • Compounds 18 (C18) and 25 (C25) exert anti-inflammatory effects in macrophages. • C18 enhanced nuclear translocation of Nrf2 and increased HO1 expression. • C25 inhibited the phosphorylation of JNK, p38 and ERK, members of the MAPKs family. • C25 reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β. • C18 and C25 may be therapeutic agents for diseases linked to inflammation.« less

Natural compound cudraflavone B shows promising anti-inflammatory properties in vitro.

PubMed

Hošek, Jan; Bartos, Milan; Chudík, Stanislav; Dall'Acqua, Stefano; Innocenti, Gabbriella; Kartal, Murat; Kokoška, Ladislav; Kollár, Peter; Kutil, Zsófia; Landa, Přemysl; Marek, Radek; Závalová, Veronika; Žemlička, Milan; Šmejkal, Karel

2011-04-25

Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor α (TNFα) gene expression and secretion by blocking the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-κB activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead.

Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

PubMed Central

Yang, Qian; Nanayakkara, Gayani K.; Drummer, Charles; Sun, Yu; Johnson, Candice; Cueto, Ramon; Fu, Hangfei; Shao, Ying; Wang, Luqiao; Yang, William Y.; Tang, Peng; Liu, Li-Wen; Ge, Shuping; Zhou, Xiao-Dong; Khan, Mohsin; Wang, Hong; Yang, Xiaofeng

2017-01-01

Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders. Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS. Results: Our data revealed following interesting findings: (1) LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2) LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells), MSCs (mesenchymal stem cells), B1-B cells and Treg (regulatory T cells); (3) LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4) LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5) Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6) LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways. Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair. PMID:29109687

Small heat shock proteins: Role in cellular functions and pathology.

PubMed

Bakthisaran, Raman; Tangirala, Ramakrishna; Rao, Ch Mohan

2015-04-01

Small heat shock proteins (sHsps) are conserved across species and are important in stress tolerance. Many sHsps exhibit chaperone-like activity in preventing aggregation of target proteins, keeping them in a folding-competent state and refolding them by themselves or in concert with other ATP-dependent chaperones. Mutations in human sHsps result in myopathies, neuropathies and cataract. Their expression is modulated in diseases such as Alzheimer's, Parkinson's and cancer. Their ability to bind Cu2+, and suppress generation of reactive oxygen species (ROS) may have implications in Cu2+-homeostasis and neurodegenerative diseases. Circulating αB-crystallin and Hsp27 in the plasma may exhibit immunomodulatory and anti-inflammatory functions. αB-crystallin and Hsp20 exhitbit anti-platelet aggregation: these beneficial effects indicate their use as potential therapeutic agents. sHsps have roles in differentiation, proteasomal degradation, autophagy and development. sHsps exhibit a robust anti-apoptotic property, involving several stages of mitochondrial-mediated, extrinsic apoptotic as well as pro-survival pathways. Dynamic N- and C-termini and oligomeric assemblies of αB-crystallin and Hsp27 are important factors for their functions. We propose a "dynamic partitioning hypothesis" for the promiscuous interactions and pleotropic functions exhibited by sHsps. Stress tolerance and anti-apoptotic properties of sHsps have both beneficial and deleterious consequences in human health and diseases. Conditional and targeted modulation of their expression and/or activity could be used as strategies in treating several human disorders. The review attempts to provide a critical overview of sHsps and their divergent roles in cellular processes particularly in the context of human health and disease. Copyright © 2015. Published by Elsevier B.V.

A20-binding inhibitor of NF-κB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein β activation and protects from inflammatory disease.

PubMed

Zhou, Jingran; Wu, Ruiqiong; High, Anthony A; Slaughter, Clive A; Finkelstein, David; Rehg, Jerold E; Redecke, Vanessa; Häcker, Hans

2011-11-01

Toll-like receptors (TLRs) are expressed on innate immune cells and trigger inflammation upon detection of pathogens and host tissue injury. TLR-mediated proinflammatory-signaling pathways are counteracted by partially characterized anti-inflammatory mechanisms that prevent exaggerated inflammation and host tissue damage as manifested in inflammatory diseases. We biochemically identified a component of TLR-signaling pathways, A20-binding inhibitor of NF-κB (ABIN1), which recently has been linked by genome-wide association studies to the inflammatory diseases systemic lupus erythematosus and psoriasis. We generated ABIN1-deficient mice to study the function of ABIN1 in vivo and during TLR activation. Here we show that ABIN1-deficient mice develop a progressive, lupus-like inflammatory disease characterized by expansion of myeloid cells, leukocyte infiltrations in different parenchymatous organs, activated T and B lymphocytes, elevated serum Ig levels, and the appearance of autoreactive antibodies. Kidneys develop glomerulonephritis and proteinuria, reflecting tissue injury. Surprisingly, ABIN1-deficient macrophages exhibit normal regulation of major proinflammatory signaling pathways and mediators but show selective deregulation of the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) and its target genes, such as colony-stimulating factor 3 (Csf3), nitric oxide synthase, inducible (Nos2), and S100 calcium-binding protein A8 (S100a8). Their gene products, which are intimately linked to innate immune cell expansion (granulocyte colony-stimulating factor), cytotoxicity (inducible nitric oxide synthase), and host factor-derived inflammation (S100A8), may explain, at least in part, the inflammatory phenotype observed. Together, our data reveal ABIN1 as an essential anti-inflammatory component of TLR-signaling pathways that controls C/EBPβ activity.

Suppression of NF-κB and NF-κB-Regulated Gene Expression by Apigenin through IκBα and IKK Pathway in TRAMP Mice

PubMed Central

Shukla, Sanjeev; Shankar, Eswar; Fu, Pingfu; MacLennan, Gregory T.; Gupta, Sanjay

2015-01-01

Aberrant Nuclear Factor-κappaB (NF-κB) activation due to rapid IκBα turnover and high basal IκBα kinase (IKK) activity has been frequently observed in prostate cancer. Apigenin, a naturally occurring plant flavone, exhibits anti-proliferative, anti-inflammatory and anti-carcinogenic activities by inhibiting NF-κB pathway, through a mechanism not fully understood. We found that apigenin feeding in microgram doses (bioavailable in humans) inhibited prostate tumorigenesis in TRAMP mice by interfering with NF-κB signaling. Apigenin feeding to TRAMP mice (20 and 50 μg/mouse/day, 6 days/week for 20 weeks) exhibited significant decrease in tumor volumes of the prostate and completely abolished metastasis, which correlated with inhibition of NF-κB activation and binding to the DNA. Apigenin intake blocked phosphorylation and degradation of IκBα by inhibiting IKK activation, which in turn led to suppression of NF-κB activation. The expression of NF-κB-regulated gene products involved in proliferation (cyclin D1, and COX-2), anti-apoptosis (Bcl-2 and Bcl-xL), and angiogenesis (vascular endothelial growth factor) were also downregulated after apigenin feeding. These events correlated with the induction of apoptosis in tumor cells, as evident by increased cleaved caspase-3 labeling index in the dorsolateral prostate. Our results provide convincing evidence that apigenin inhibits IKK activation and restores the expression of IκBα, preventing it’s phosphorylation in a fashion similar to that elicited by IKK and proteasomal inhibitors through suppression of NF-κB signaling pathway. PMID:26379052

Synthesis, Characterization, and Anti-Inflammatory Activities of Methyl Salicylate Derivatives Bearing Piperazine Moiety.

PubMed

Li, Jingfen; Yin, Yong; Wang, Lisheng; Liang, Pengyun; Li, Menghua; Liu, Xu; Wu, Lichuan; Yang, Hua

2016-11-23

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.

Benzimidazole--ibuprofen/mesalamine conjugates: potential candidates for multifactorial diseases.

PubMed

Bansal, Yogita; Kaur, Maninder; Silakari, Om

2015-01-07

Ibuprofen (IB) and mesalamine (MES) are commonly used NSAIDs whereas benzimidazole (BZ) and 2-aminobenzimidazole (ABZ) are important pharmacophore for immunomodulatory activities. In the present study, IB and MES were coupled with variedly substituted BZ or ABZ nucleus to synthesize IB-BZ (2a-2e), IB-ABZ (3a-3e), MES-BZ (4a-4e) and MES-ABZ (5a-5e) chimeric conjugates as novel compounds that could elicit both anti-inflammatory and immunomodulatory activities. Each compound retained the anti-inflammatory activity of the parent NSAID. The BZ conjugates (2 and 4) were found immunostimulatory whereas the ABZ conjugates (3 and 5) were immunosuppressive. Each compound also exhibited good antioxidant activity, which is attributed to the electron rich BZ and ABZ nuclei. Compound 2a, 2e, 3a, 3e and 5b exhibited the most significant anti-inflammatory and immunomodulatory activities. Hence, these were evaluated for in vivo acute gastric ulcerogenicity. The compounds were safe to gastric mucosa, probably due to masking of the free -COOH group of IB and MES, and/or to the BZ nucleus itself. A benzoyl group at 5-position of BZ and ABZ incurred maximum immunostimulatory activity. In contrast, a -NO2 group incurred the maximum immunosuppressive action. Docking analysis revealed the compounds to be more selective towards COX-2 enzyme, which support the gastroprotective activity. These results suggest that the compounds can be taken as lead for development of new drugs for the treatment of immune related inflammatory disorders, such as cancer and rheumatoid arthritis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Neuroprotection and enhanced neurogenesis by extract from the tropical plant Knema laurina after inflammatory damage in living brain tissue.

PubMed

Häke, Ines; Schönenberger, Silvia; Neumann, Jens; Franke, Katrin; Paulsen-Merker, Katrin; Reymann, Klaus; Ismail, Ghazally; Bin Din, Laily; Said, Ikram M; Latiff, A; Wessjohann, Ludger; Zipp, Frauke; Ullrich, Oliver

2009-01-03

Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic survey, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that alcoholic extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protected living brain tissue from microglia-mediated inflammatory damage at a concentration of 30 microg/ml. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, IkB-phosphorylation and subsequently NF-kB-translocation in microglia cells. K. laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from K. laurina promotes also neurogenesis in living brain tissue after oxygen-glucose deprivation. In conclusion, extract from K. laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury.

Cistanches Herba: An overview of its chemistry, pharmacology, and pharmacokinetics property.

PubMed

Fu, Zhifei; Fan, Xiang; Wang, Xiaoying; Gao, Xiumei

2018-06-12

Cistanches Herba is an Orobanchaceae parasitic plant. As a commonly used Traditional Chinese Medicine (TCM), its traditional functions include treating kidney deficiency, impotence, female infertility and senile constipation. Chemical analysis of Cistanches Herba revealed that phenylethanoid glycosides, iridoids, lignans, oligosaccharides, and polysaccharides were the main constituents. Pharmacological studies demonstrated that Cistanches Herba exhibited neuroprotective, immunomodulatory, hormonal balancing, anti-fatigue, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, anti-viral, and anti-tumor effects, etc. The aim of this review is to provide updated, comprehensive and categorized information on the phytochemistry, pharmacological research and pharmacokinetics studies of the major constituents of Cistanches Herba. The literature search was conducted by systematic searching multiple electronic databases including SciFinder, ISI Web of Science, PubMed, Google Scholar and CNKI. Information was also collected from journals, local magazines, books, monographs. To date, more than 100 compounds have been isolated from this genus, include phenylethanoid glycosides, carbohydrates, lignans, iridoids, etc. The crude extracts and isolated compounds have exhibited a wide range of in vitro and in vivo pharmacologic effects, such as neuroprotective, immunomodulatory, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, and anti-tumor effects. The phenylethanoid glycosides, echinacoside and acteoside have attracted the most attention for their significantly neuropharmacology effects. Pharmacokinetic studies of echinacoside and acteoside also have also been summarized. Phenylethanoid glycosides have demonstrated wide pharmacological actions and have great clinical value if challenges such as poor bioavailability, fast and extensive metabolism are addressed. Apart from phenylethanoid glycosides, other constituents of Cistanches Herba, their pharmacological activities and underlying mechanisms are also need to be studied further. Copyright © 2017. Published by Elsevier B.V.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

PubMed

Hoff Brait, Débora Regina; Mattos Vaz, Márcia Soares; da Silva Arrigo, Jucicléia; Borges de Carvalho, Luciana Noia; Souza de Araújo, Flávio Henrique; Vani, Juliana Miron; da Silva Mota, Jonas; Cardoso, Claudia Andrea Lima; Oliveira, Rodrigo Juliano; Negrão, Fábio Juliano; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2015-12-01

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Alpinetin attenuates inflammatory responses by interfering toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced mastitis in mice.

PubMed

Chen, Haijin; Mo, Xiaodong; Yu, Jinlong; Huang, Zonghai

2013-09-01

Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to exhibit anti-inflammatory properties. However, the effect of alpinetin on mastitis has not been investigated. The aim of this study was to investigate the protective effect of alpinetin against lipopolysaccharide (LPS)-induced mastitis and to clarify the possible mechanism. In the present study, primary mouse mammary epithelial cells and an LPS-induced mouse mastitis model were used to investigate the effect of alpinetin on mastitis and the possible mechanism. In vivo, we observed that alpinetin significantly attenuated the infiltration of neutrophilic granulocytes, and the activation of myeloperoxidase; down-regulated the level of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6; inhibited the phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4, caused by LPS. In vitro, we also observed that alpinetin inhibited the expression of TLR4 and the production of TNF-α, IL-1β and IL-6 in LPS-stimulated primary mouse mammary epithelial cells. However, alpinetin could not inhibit the production of IL-1β and IL-6 in TNF-α-stimulated primary mouse mammary epithelial cells. In conclusion, our results suggest that the anti-inflammatory effects of alpinetin against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. Alpinetin may be a promising potential therapeutic reagent for mastitis treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Perineural Dexmedetomidine Attenuates Inflammation in Rat Sciatic Nerve via the NF-κB Pathway

PubMed Central

Huang, Yan; Lu, Yi; Zhang, Lei; Yan, Jia; Jiang, Jue; Jiang, Hong

2014-01-01

Recent studies have shown that dexmedetomidine exerts an anti-inflammatory effect by reducing serum levels of inflammatory factors, however, the up-stream mechanism is still unknown. The transcription factor NF-κB enters the nucleus and promotes the transcription of its target genes, including those encoding the pro-inflammatory cytokines IL-6 and TNF-α. In this study, we established a rat model that simulates a clinical surgical procedure to investigate the anti-inflammatory effect of perineural administration of dexmedetomidine and the underlying mechanism. Dexmedetomidine reduced the sciatic nerve levels of IL-6 and TNF-α at both the mRNA and protein level. Dexmedetomidine also inhibited the translocation of activated NF-κB to the nucleus and the binding activity of NF-κB. The anti-inflammatory effect is confirmed to be dose-dependent. Finally, pyrrolidine dithiocarbamate also reduced the levels of IL-6 and TNF-α and the activation of NF-κB. In conclusion, dexmedetomidine inhibited the nuclear translocation and binding activity of activated NF-κB, thus reducing inflammatory cytokines. PMID:24663080

Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats.

PubMed

Doss, Hari Madhuri; Dey, Chandrima; Sudandiradoss, C; Rasool, Mahaboob Khan

2016-03-01

The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug. Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1. In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-κB, PYCARD/ASC, and NLRP3. Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies

PubMed Central

Silva, Rosa H. M.; Lima, Nathália de Fátima M.; Lopes, Alberto J. O.; Vasconcelos, Cleydlenne C.; de Mesquita, José W. C.; de Mesquita, Ludmilla S. S.; Lima, Fernando C. V. M.; Ribeiro, Maria N. de S.; Ramos, Ricardo M.; Cartágenes, Maria do Socorro de S.; Garcia, João B. S.

2017-01-01

Borreria verticillata (L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of B. verticillata hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by in vivo and in silico studies. In vivo assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0.9% NaCl control group (CTRL), 10 mg/kg memantine (MEM), 10 mg/kg indomethacin (INDO), 500 mg/kg EHBv (EHBv 500), 25 mg/kg FAc (FAc 25) and 50 mg/kg FAc (FAc 50). EHBv, FAc 25 and 50 treatments exhibited anti-edematous and peripheral antinociceptive effects. For in silico assessment, compounds identified in FAc were subjected to molecular docking with COX-2, GluN1a and GluN2B. Ursolic acid (UA) was the compound with best affinity parameters (binding energy and inhibition constant) for COX-2, GluN1a, GluN2B, and was selected for further analysis with molecular dynamics (MD) simulations. In MD simulations, UA exhibited highly frequent interactions with residues Arg120 and Glu524 in the COX-2 active site and NMDA, whereby it might prevent COX-2 and NMDA receptor activation. Treatment with UA 10 mg/Kg showed peripheral and central antinociceptive effect. The antinociceptive effect of B. verticillata might be predominantly attributed to peripheral actions, including the participation of anti-inflammatory components. Ursolic acid is the main active component and seems to be a promising source of COX-2 inhibitors and NMDA receptor antagonists. PMID:28588488

Acai Juice Attenuates Atherosclerosis Through Antioxidant and Anti-Inflammatory Effects in ApoE Deficient Mice

USDA-ARS?s Scientific Manuscript database

Introduction: Acai fruit (Euterpe oleracea Mart.) has been shown to exhibit extremely high antioxidant capacity. Antioxidant capacities and anti-inflammatory effects of acai pulp or acai juices have been studied in human, animal and cell culture models. However, their potential effects on atheroscl...

Antioxidative and Anti-Inflammatory Activities of Galloyl Derivatives and Antidiabetic Activities of Acer ginnala

PubMed Central

Park, Kwan Hee; Yoon, Kyu Hyeong; Yin, Jun; Le, Thi Tam; Ahn, Hye Sin; Yoon, Seong Hye

2017-01-01

Chromatographic isolation of the 80% MeOH extract of Acer ginnala (AG) yielded seven galloyl derivatives: gallic acid (1), ginnalin B (2), acertannin (3), maplexin D (4), maplexin E (5), quercetin-3-O-(2′′-galloyl)-α-L-rhamnopyranoside (6), and kaempferol-3-O-(2′′-galloyl)-α-L-rhamnopyranoside (7). This is the first study to report the isolation of compounds 4 and 5 from AG. Galloyl derivatives 3–7 exhibited potent radical scavenging activities, with 5 and 7 showing particularly strong inhibitory activities against nitric oxide production in lipopolysaccharides- (LPS-) stimulated RAW264.7 cells. In addition, oral administration of AG extract (500 mg/kg b.w.) improved symptoms of hyperglycemia and blunted the increases in serum GOT/GPT levels in a rat model of streptozotocin-induced diabetes. These results suggest that galloyl derivatives (1–7) are antioxidant and anti-inflammatory agents and that AG extract has potential as a functional material or novel herbal medicine for treating diabetes mellitus. PMID:28348624

Levetiracetam exhibits protective properties on rat Schwann cells in vitro.

PubMed

Stettner, Mark; Dehmel, Thomas; Mausberg, Anne K; Köhne, Angelika; Rose, Christine R; Kieseier, Bernd C

2011-09-01

Oxidative stress and inflammation represent pathways causing substantial damage to the peripheral nervous system. Levetiracetam (LEV) is a commonly used antiepileptic drug targeting high-voltage activated N-type calcium channels. Recent evidence suggests that LEV may also act as a histone deacetylase inhibitor, suggesting that this drug exhibits both anti-inflammatory and anti-oxidative effects, and as such may represent an interesting candidate for treating inflammatory diseases affecting the peripheral nerve. Therefore, we analysed the influence of LEV ex vivo on purified Schwann cells from neonatal P3 rats as well as on dorsal root ganglia prepared from E15 rat embryos. LEV diminished a lipopolysaccharide (LPS)-induced increase of the pro-inflammatory signature molecules tumour necrosis factor alpha, matrix metalloproteinase 9 (MMP-9), and caspase 6. Furthermore, LEV decreased LPS-induced cell death and protected cells against oxidative stress in a glutamate-based oxidative stress model. MMP-2 activity, usually elevated during myelination and repair, was also found to be up-regulated following LEV, while LEV exhibited no negative effects on myelination. Intracellular sodium or calcium concentrations were unaltered by LEV. Thus, LEV may be a promising, well-tolerated drug that - besides its antiepileptic potential - mediates anti-inflammatory, anti-oxidative, and anti-apoptotic properties that may potentially be useful in treating diseases of the peripheral nerve. © 2011 Peripheral Nerve Society.

Bioactive constituents in pulses and their health benefits.

PubMed

Singh, Balwinder; Singh, Jatinder Pal; Shevkani, Khetan; Singh, Narpinder; Kaur, Amritpal

2017-03-01

Pulses are good sources of bioactive compounds such as polyphenols, phytosterols and non-digestible carbohydrates that play important physiological as well as metabolic roles. These compounds vary in concentration amongst different pulse species and varieties. Pulse seed coats are rich in water-insoluble fibres and polyphenols (having high antioxidant activities), while cotyledons contain higher soluble fibres, oligosaccharides, slowly digestible and resistant starch content. Ferulic acid is the most abundant phenolic acid present in pulses, while flavonol glycosides, anthocyanins and tannins are responsible for the seed coat colour. Sitosterol (most abundant), stigmasterol, and campesterol are the major phytosterols present in pulses. Pulse fibres, resistant starch and oligosaccharides function as probiotics and possess several other health benefits such as anti-inflammatory, anti-tumour, and reduce glucose as well as lipid levels. Beans and peas contain higher amounts of oligosaccharides than other pulses. Processing methods affect resistant starch, polyphenol composition and generally increase antioxidant activities of different pulses. In this review, the current information on pulse polyphenols, phytosterols, resistant starch, dietary fibre, oligosaccharides, antioxidant and associated health benefits are discussed.

The Anticancer Activity of Sea Buckthorn [Elaeagnus rhamnoides (L.) A. Nelson

PubMed Central

Olas, Beata; Skalski, Bartosz; Ulanowska, Karolina

2018-01-01

Various parts of sea buckthorn [Elaeagnus rhamnoides (L.) A. Nelson], particularly the berries, known also as seaberries, or Siberian pineapples, are characterized by a unique composition of bioactive compounds: phenolic compounds, vitamins (especially vitamin C), unsaturated fatty acids, and phytosterols such as beta-sitosterol. These berries, together with the juices, jams, and oils made from them, have a range of beneficial antioxidant, anti-inflammatory, and anticancer effects. This short review discusses whether sea buckthorn may represent a “golden mean” for the treatment of cancers: It has anti-proliferation properties and can induce apoptosis and stimulate the immune system, and sea buckthorn oil counteracts many side effects of chemotherapy by restoring kidney and liver function, increasing appetite, and keeping patients in general good health. Although the anticancer activity of sea buckthorn has been confirmed by many in vitro and animal in vivo studies, the treatment and prophylactic doses for humans are unknown. Therefore, greater attention should be paid to the development of well-controlled and high-quality clinical experiments in this area. PMID:29593547

Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition.

PubMed

Lu, Li; Qin, Aiping; Huang, Hongbiao; Zhou, Ping; Zhang, Chuanyin; Liu, Ningning; Li, Shujue; Wen, Guanmei; Zhang, Change; Dong, Weihua; Wang, Xuejun; Dou, Q Ping; Liu, Jinbao

2011-05-11

Shikonin, extracted from medicinal Chinese herb (Lithospermum erythrorhizo), was reported to exert anti-inflammatory and anti-cancer effects both in vitro and in vivo. We have found that proteasome was a molecular target of shikonin in tumor cells, but whether shikonin targets macrophage proteasome needs to be investigated. In the current study, we report that shikonin inhibited inflammation in mouse models as efficiently as dexamethasone. Shikonin at 4 μM reduced the Lipopolysaccharides (LPS)-mediated TNFα release in rat primary macrophage cultures, and blocked the translocation of p65-NF-κB from the cytoplasm to the nucleus, associated with decreased proteasomal activity. Consistently, shikonin accumulated IκB-α, an inhibitor of NF-κB, and ubiquitinated proteins in rat primary macrophage cultures, demonstrating that the proteasome is a target of shikonin under inflammatory conditions. Shikonin also induced macrophage cell apoptosis and cell death. These results demonstrate for the first time that proteasome inhibition by shikonin contributes to its anti-inflammatory effect. The novel finding about macrophage proteasome as a target of shikonin suggests that this medicinal compound has great potential to be developed into an anti-inflammatory agent. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis, evaluation and modeling of some triazolothienopyrimidinones as anti-inflammatory and antimicrobial agents.

PubMed

Bekhit, Adnan A; Farghaly, Ahmed M; Shafik, Ragab M; Elsemary, Mona Ma; El-Shoukrofy, Mai S; Bekhit, Alaa El-Din A; Ibrahim, Tamer M

2017-06-01

New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. Compounds 7a, 10a and 11a showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC 50 values of 1.39, 1.22 and 0.56 μM, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2. Compound 12b displayed antimicrobial activity comparable to that of ampicillin against Escherichia coli while compounds 6 and 11c were similar to ampicillin against Staphylococcus aureus. In addition, compounds 7a, 9a, 10b and 11c showed dual anti-inflammatory/antimicrobial activities. This work represents a promising matrix for developing new potential anti-inflammatory, antimicrobial and dual antimicrobial/anti-inflammatory candidates. [Formula: see text].

Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis.

PubMed

Benevides Bahiense, Jhéssica; Marques, Franciane Martins; Figueira, Mariana Moreira; Vargas, Thais Souza; Kondratyuk, Tamara P; Endringer, Denise Coutinho; Scherer, Rodrigo; Fronza, Marcio

2017-12-01

Sambucus australis Cham. & Schltdl. (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. Chemical composition was assessed by LC-MS/MS. Antioxidant activities in the DPPH (IC 50 43.5 and 66.2 μg/mL), FRAP (IC 50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC 50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects.

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.

Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

PubMed Central

Galvez-Llompart, María; Zanni, Riccardo; García-Domenech, Ramón

2011-01-01

One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds. PMID:22272145

Oxymatrine lightened the inflammatory response of LPS-induced mastitis in mice through affecting NF-κB and MAPKs signaling pathways.

PubMed

Yang, Zhengtao; Yin, Ronglan; Cong, Yunfeng; Yang, Zhanqing; Zhou, Ershun; Wei, Zhengkai; Liu, Zhicheng; Cao, Yongguo; Zhang, Naisheng

2014-12-01

Mastitis, an inflammatory reaction of the mammary gland, is recognized as one of the most costly diseases in dairy cattle. Oxymatrine, one of the alkaloids extracted from Chinese herb Sophora flavescens Ait, has been reported to have many biological activities, such as anti-inflammatory, anti-virus, and anti-hepatic fibrosis properties. The aim of this study was to investigate the protective effect and the anti-inflammatory mechanism of oxymatrine on lipopolysaccharide (LPS)-induced mastitis in mice. The mouse mastitis was induced by 10 μg of LPS for 24 h. Oxymatrine was intraperitoneally administered with the dose of 30, 60, and 120 mg/kg 1 h before and 12 h after LPS induction. The results showed that oxymatrine significantly attenuated the damage of the mammary gland induced by LPS. Oxymatrine inhibited the phosphorylation of NF-κB p65 and IκB in NF-κB signal pathway and reduced the phosphorylation of p38, ERK, and JNK in mitogen-activated protein kinase (MAPKs) signal pathway. The results showed that oxymatrine had a protective effect on LPS-induced mastitis, and the anti-inflammatory mechanism of oxymatrine was related to the inhibition of NF-κB and MAPKs signal pathways.

Experimental colitis in mice is attenuated by topical administration of chlorogenic acid.

PubMed

Zatorski, Hubert; Sałaga, Maciej; Zielińska, Marta; Piechota-Polańczyk, Aleksandra; Owczarek, Katarzyna; Kordek, Radzisław; Lewandowska, Urszula; Chen, Chunqiu; Fichna, Jakub

2015-06-01

Epidemiological data suggest that the consumption of polyphenol-rich foods reduces the incidence of cancer, coronary heart disease, and inflammation. Chlorogenic acid (CGA), an ester of caffeic and quinic acids, is one of the most abundant polyphenol compounds in human diet with proven biological effectiveness both in vitro and in vivo. The aim of the study is to investigate the possible anti-inflammatory effect of CGA in the gastrointestinal (GI) tract and its mechanism of action. We used a well-established model of colitis, induced by intracolonic (i.c.) administration of trinitrobenzenesulfonic acid (TNBS) in mice. The anti-inflammatory effect of CGA in the colon was evaluated based on the clinical and macroscopic and microscopic parameters. To investigate the mechanism of protective action of CGA, myeloperoxidase (MPO), H2O2, and NF-κB levels were assessed in the colon tissue. CGA administered i.c. at the dose of 20 mg/kg (two times daily) protected against TNBS-induced colitis more effectively than the same dose administered orally (p.o.), as evidenced by significantly lower macroscopic and ulcer scores. Furthermore, CGA (20 mg/kg, i.c.) reduced neutrophil infiltration, as demonstrated by decreased MPO activity. Moreover, CGA suppressed activation of NF-κB, as evidenced by lower levels of phospho-NF-κB/NF-κB ratio in the tissue. CGA did not affect the oxidative stress pathways. CGA exhibits anti-inflammatory properties through reduction of neutrophil infiltration and inhibition of NF-κB-dependent pathways. Our results suggest that CGA may have the potential to become a valuable supplement in the treatment of GI diseases.

Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

PubMed Central

2014-01-01

Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785

Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark.

PubMed

Eo, Hyun Ji; Park, Jae Ho; Park, Gwang Hun; Lee, Man Hyo; Lee, Jeong Rak; Koo, Jin Suk; Jeong, Jin Boo

2014-06-25

Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity.

3-methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents.

PubMed

Abdellatif, Khaled R A; Lamie, Phoebe F; Omar, Hany A

2016-01-01

In a new group of 3-methyl-2-phenyl-1-substituted-indole derivatives (10a-f), the indomethacin analogs were prepared via the Fisher indole synthesis reaction of propiophenone with appropriately substituted phenylhydrazine hydrochloride. This is followed by the insertion of the appropriate benzyl or benzoyl fragment. All the synthesized compounds were evaluated for their anti-inflammatory (in vitro and in vivo) and analgesic activities. The methanesulphonyl derivatives 10d, e and f showed the highest anti-inflammatory (in vitro and in vivo) and analgesic activities. In addition, molecular docking studies were performed on compounds 10a-f and the results were in agreement with that obtained from the in vitro COX inhibition assays. The significant anti-inflammatory and analgesic activities exhibited by 10d and 10e warrant continued preclinical development as potential anti-inflammatory and analgesic agents.

Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida.

PubMed

Li, Chunlong; Chen, Mengrou; Li, Xiaojie; Yang, Meifeng; Wang, Ying; Yang, Xinwang

2017-03-01

The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm (Eisenia foetida). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro 5-lipoxygenase and anti-oxidant activities of South African medicinal plants commonly used topically for skin diseases.

PubMed

Frum, Y; Viljoen, A M

2006-01-01

An investigation was undertaken to determine the possible mechanisms of action of medicinal plants used for dermatological pathologies. A total of 14 plant species were selected from the readily available ethnobotanical literature. 5-Lipoxygenase and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays were used to determine the anti-inflammatory activity and the anti-oxidant activity of selected medicinal plants, respectively. Both aqueous and methanol extracts were tested. Among the plants screened, four species (Croton sylvaticus, Warburgia salutaris, Pentanisia prunelloides, and Melianthus comosus) displayed promising 5-lipoxygenase inhibitory activity with IC(50) values <61 ppm. A large number of plants exhibited significant anti-oxidant activities with IC(50) values between 5.27 and 83.36 ppm. Aqueous extracts of M. comosus exhibited the most potent anti-inflammatory and anti-oxidant activity.

Identification of new anti-inflammatory agents based on nitrosporeusine natural products of marine origin.

PubMed

Philkhana, Satish Chandra; Verma, Abhishek Kumar; Jachak, Gorakhnath R; Hazra, Bibhabasu; Basu, Anirban; Reddy, D Srinivasa

2017-07-28

Nitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential. Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition, these compounds suppressed several pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), and thereby can be emerged as potent anti-inflammatory compounds. Furthermore, all possible isomers of lead compound 25 were synthesized, characterized and profiled in same set of assays and found that one of the enantiomer (-)-25a was superior among them. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Anti-inflammatory and in-vitro antibacterial activities of Traditional Chinese Medicine Formula Qingdaisan.

PubMed

Zhao, Xinghua; He, Xin; Zhong, Xiuhui

2016-12-05

Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS. Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control. Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn't show any significant antibacterial activity in vitro. The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn't have antibacterial activity to selected strains in vitro.

Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.

PubMed

Zhu, Heping; Xu, Tingting; Qiu, Chenyu; Wu, Beibei; Zhang, Yali; Chen, Lingfeng; Xia, Qinqin; Li, Chenglong; Zhou, Bin; Liu, Zhiguo; Liang, Guang

2016-10-04

A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Comparative anti-psoriatic efficacy studies of clobetasol loaded chitin nanogel and marketed cream.

PubMed

Panonnummal, Rajitha; Jayakumar, R; Sabitha, M

2017-01-01

In the present study chitin nanogel loaded with anti-psoriatic drug clobetasol was developed (CLCNG) for its topical delivery in psoriasis. CLCNG had the particle size of 132±14nm, with gel like consistency, stability in refrigerator, having higher drug release properties at acidic pH. CLCNG exhibited significant toxicity towards HaCaT and THP-1cell lines by MTT assay. The uptake of nanogel by HaCaT cell lines was confirmed by fluorescent microscopy. CLCNG at 0.35mg/ml exhibited significant anti-inflammatory activity with an average of 65% and 70% inhibition in COX and LOX activities expressed in THP-1 cells. In vitro skin permeation studies revealed the increased transdermal flux with fragmented stratum corneum and loosened epidermal layers in CLCNG treated samples, compared with control drug solution. The in vivo anti-psoriatic studies done on imiquimod model confirmed the potential benefits of the nanogel for the topical delivery of clobetasol in psoriasis. Copyright © 2016 Elsevier B.V. All rights reserved.

Two new triterpenes from the roots of Pfaffia glomerata.

PubMed

Lian, Lian; Feng, Yuan; Li, Yan-Wu; Bei, Bei; Tang, Ye-Tian; Wang, Hao; Feng, Qing-Mei; Chen, Gang

2018-04-02

Pfaffia paniculata is a commercialized dietary supplement used as the substitute for the Asian ginseng in Brazil. We conducted the systematic isolation of the EtOAc fraction with anti-inflammatory effect and two new triterpenoids, along with 26 known compounds were characterized by means of MS and NMR analysis. Interestingly, the new compound 1 is the first seco-ring triterpenoid reported in the Pfaffia genus. Furthermore, among the known compounds, 14 and 15 exhibited anti-inflammatory activity in Caco-2 cells, but two new compounds showed no anti-inflammatory.

Gelam Honey Attenuates Carrageenan-Induced Rat Paw Inflammation via NF-κB Pathway

PubMed Central

Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

2013-01-01

The activation of nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o.) and NSAID Indomethacin (10 mg/kg, p.o.), in two time points (1 and 7 days). Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50) and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α. PMID:24015236

Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.

PubMed

Zhang, Linjie; Yang, Li

2014-12-26

Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor κ-light-chain-enhancer of activated B cells κB (NF-κB) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-κB pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke.

Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid.

PubMed

Huang, Wen-Cheng; Tsai, Tsung-Hsien; Chuang, Lu-Te; Li, You-Yi; Zouboulis, Christos C; Tsai, Po-Jung

2014-03-01

Propionibacterium acnes (P. acnes) is a commensal bacterium which is possibly involved in acne inflammation. The saturated fatty acid, lauric acid (C12:0) has been shown to possess antibacterial and anti-inflammatory properties against P. acnes. Little is known concerning the potential effects of its decanoic counterpart, capric acid (C10:0). To examine the antibacterial and anti-inflammatory activities of capric acid against P. acnes and to investigate the mechanism of the anti-inflammatory action. The antimicrobial activity of fatty acids was detected using the broth dilution method. An evaluation of P. acnes-induced ear edema in mice was conducted to evaluate the in vivo anti-inflammatory effect. To elucidate the in vitro anti-inflammatory effect, human SZ95 sebocytes and monocytic THP-1 cells were treated with P. acnes alone or in the presence of a fatty acid. The mRNA levels and secretion of pro-inflammatory cytokines were measured by qRT-PCR and enzyme immunoassay, respectively. NF-κB activation and MAPK expression were analyzed by ELISA and Western blot, respectively. Lauric acid had stronger antimicrobial activity against P. acnes than capric acid in vitro and in vivo. However, both fatty acids attenuated P. acnes-induced ear swelling in mice along with microabscess and significantly reduced interleukin (IL)-6 and CXCL8 (also known as IL-8) production in P. acnes-stimulated SZ95 sebocytes. P. acnes-induced mRNA levels and secretion of IL-8 and TNF-α in THP-1 cells were suppressed by both fatty acids, which inhibited NF-κB activation and the phosphorylation of MAP kinases. Our data demonstrate that both capric acid and lauric acid exert bactericidal and anti-inflammatory activities against P. acnes. The anti-inflammatory effect may partially occur through the inhibition of NF-κB activation and the phosphorylation of MAP kinases. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

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

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16more » weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.« less

Anti-inflammatory effect of ethanolic extract from Myagropsis myagroides on murine macrophages and mouse ear edema

PubMed Central

2012-01-01

Background This study aims to investigate anti-inflammatory effect of ethanolic extract of Myagropsis myagroides (EMM) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and the phorbol 12-myristate 13-acetate (PMA)-induced ear edema in mice, and to clarify its underlying molecular mechanisms. Methods The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blotting. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunocytochemistry and reporter gene assay, respectively. PMA-induced mouse ear edema was used as the animal model of inflammation. Anti-inflammatory compounds in EMM were isolated using high-performance liquid chromatography and identified by nuclear magnetic resonance. Results EMM significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner and suppressed the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. EMM strongly suppressed nuclear translocation of NF-κB by preventing degradation of inhibitor of κB-α as well as by inhibiting phosphorylation of Akt and MAPKs. EMM reduced ear edema in PMA-induced mice. One of the anti-inflammatory compounds in EMM was identified as 6,6’-bieckol. Conclusions These results suggest that the anti-inflammatory properties of EMM are associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the inhibition of NF-κB pathway in LPS-stimulated macrophages. PMID:23031211

Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents.

PubMed

Bhati, Sudhir Kumar; Kumar, Ashok

2008-11-01

Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5-b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h), and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4-thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present study. The structure of these newly synthesized compounds were confirmed by their analytical and spectral data. These compounds were also evaluated for their anti-inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most active anti-inflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin.

Anti-pruritic and anti-inflammatory effects of oxymatrine in a mouse model of allergic contact dermatitis.

PubMed

Xu, Xiaoyun; Xiao, Wei; Zhang, Zhe; Pan, Jianhao; Yan, Yixi; Zhu, Tao; Tang, Dan; Ye, Kaihe; Paranjpe, Manish; Qu, Lintao; Nie, Hong

2018-05-31

Allergic contact dermatitis (ACD) is a highly prevalent inflammatory disease of the skin. As a result of the complex etiology in ACD, therapeutic compounds targeting refractory pruritus in ACD lack efficacy and lead to numerous side effects. In this study, we investigated the anti-pruritic effects of oxymatrine (OMT) and explored its mechanism of action in a mouse model of ACD. 72 male SPF C57BL/6 mice were randomly divided into control group, ACD model group, dexamethasone positive control group (0.08 mg kg -1 ) and 3 OMT groups (80, 40, 20 mg kg -1 ). OMT was administrated by intraperitoneal injection 1 h before video recording on day 10, 24 h after 2nd challenge with SADBE. Cheek skin fold thickness was measured before treatment and after recording. H&E staining was used for pathological observation. RT-qPCR, Immunohistochemistry and LEGENDplexTM assay were used to detect cytokines levels. The population of Treg cells in peripheral blood were detected via flow cytometry. OMT treatment significantly decreases the skin inflammation and scratching bouts. It rescues defects in epidermal keratinization and inflammatory cell infiltration in ACD mice. Administration of OMT significantly reduced levels of IFN-γ, IL-13, IL-17A, TNF-α, IL-22 and mRNA expression of TNF-α and IL-1β. Furthermore, it increased the percentage of Treg cells in peripheral blood of ACD mice. We have demonstrated that OMT exhibits anti-pruritic and anti-inflammatory effects in ACD mice by regulating inflammatory mediators. OMT might emerge as a potential drug for the treatment of pruritus and skin inflammation in the setting of ACD. Copyright © 2018. Published by Elsevier B.V.

Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

PubMed

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2013-02-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.

Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium

PubMed Central

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2012-01-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. PMID:22740381

Chemopreventive properties of raisins originating from Greece in colon cancer cells.

PubMed

Kountouri, Aggeliki M; Gioxari, Aristea; Karvela, Evangelia; Kaliora, Andriana C; Karvelas, Michalis; Karathanos, Vaios T

2013-02-26

Colorectal cancer is one of the major causes of cancer-related mortality in humans in both developed and developing countries. Dietary patterns influence the risk of colon cancer development, while plant-derived foods have gained great interest, due to the high content of antioxidants. Corinthian raisins (Currants, CR) and Sultanas (S) (Vitis vinifera L., Vitaceae) are dried vine fruits produced in Greece with many culinary uses in both the Mediterranean and the Western nutrition. In the present study, we investigated the effects of CR and S on human colon cancer cells. Methanol extracts of CR and S were used at different concentrations. The total polyphenol content and anti-radical activity were measured by Folin-Ciocalteu and DPPH, respectively. Antioxidant, anti-inflammatory and anti-proliferative effects on HT29 cell culture were evaluated. All extracts exhibited DPPH˙ scavenging activity in a dose-dependent manner. Both products suppressed cell proliferation, while the levels of glutathione and cyclooxygenase 2 were significantly decreased. A significant reduction in IL-8 levels and NF-kappaB p65 activation was also observed. Both antioxidant and anti-inflammatory effects were dependent on the duration of exposure. Results indicate that the methanol extracts of CR and S exhibit anti-radical activity in vitro, as well as cancer preventive efficacy on colon cancer cells, with S having slightly higher activity. The beneficial properties of these unique dried grapes are attributed to their high content of phenolic compounds.

A new acylated flavonol from the aerial parts of Asteriscus maritimus (L.) Less (Asteraceae).

PubMed

Ezzat, Marwa I; Ezzat, Shahira M; El Deeb, Kadriya S; El Fishawy, Ahlam M; El-Toumy, Sayed A

2016-08-01

Phytochemical investigation of the flowering aerial parts of Asteriscus maritimus (L.) Less (Asteraceae) led to the isolation of a new compound: patuletin 7-O-β-D-[(2″'S) 6″(3″'-hydroxy-2″'-methyl-propanoyl)] glucopyranoside, together with five known metabolites; β-sitosterol 2, chlorogenic acid 3, P-hydroxy -methylbenzoate 4, luteolin 5 and protocatechuic acid 6. The structures of the isolated compounds were determined by comprehensive analyses of its 1D and 2D NMR, HRMS and compared with previously known analogues. The ethanolic extract of the flowering aerial parts of A. maritimus was found to be safe (LD50 = 4.6 mg/kg) and possess significant antioxidant and anti-inflammatory activities and this was in accordance with its high phenolic content (107.36 ± 0.051 mg GAE/g extract).

Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER.

PubMed

Yamaguchi, Junichi; Kawada-Watanabe, Erisa; Koyanagi, Ryo; Arashi, Hiroyuki; Sekiguchi, Haruki; Nakao, Koichi; Tobaru, Tetsuya; Tanaka, Hiroyuki; Oka, Toshiaki; Endo, Yasuhiro; Saito, Katsumi; Uchida, Tatsuro; Matsui, Kunihiko; Ogawa, Hiroshi; Hagiwara, Nobuhisa

2018-05-05

We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia. This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach. Copyright © 2018 Elsevier B.V. All rights reserved.

PTP1B Inhibitory and Anti-Inflammatory Effects of Secondary Metabolites Isolated from the Marine-Derived Fungus Penicillium sp. JF-55

PubMed Central

Lee, Dong-Sung; Jang, Jae-Hyuk; Ko, Wonmin; Kim, Kyoung-Su; Sohn, Jae Hak; Kang, Myeong-Suk; Ahn, Jong Seog; Kim, Youn-Chul; Oh, Hyuncheol

2013-01-01

Protein tyrosine phosphatase 1B (PTP1B) plays a major role in the negative regulation of insulin signaling, and is thus considered as an attractive therapeutic target for the treatment of diabetes. Bioassay-guided investigation of the methylethylketone extract of marine-derived fungus Penicillium sp. JF-55 cultures afforded a new PTP1B inhibitory styrylpyrone-type metabolite named penstyrylpyrone (1), and two known metabolites, anhydrofulvic acid (2) and citromycetin (3). Compounds 1 and 2 inhibited PTP1B activity in a dose-dependent manner, and kinetic analyses of PTP1B inhibition suggested that these compounds inhibited PTP1B activity in a competitive manner. In an effort to gain more biological potential of the isolated compounds, the anti-inflammatory effects of compounds 1–3 were also evaluated. Among the tested compounds, only compound 1 inhibited the production of NO and PGE2, due to the inhibition of the expression of iNOS and COX-2. Penstyrylpyrone (1) also reduced TNF-α and IL-1β production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of penstyrylpyrone (1) on the pro-inflammatory mediators and NF-κB DNA binding activity were associated with the HO-1 expression. Therefore, these results suggest that penstyrylpyrone (1) suppresses PTP1B activity, as well as the production of pro-inflammatory mediators via NF-κB pathway, through expression of anti-inflammatory HO-1. PMID:23612372

Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.

PubMed

Aggarwal, Bharat B; Yuan, Wei; Li, Shiyou; Gupta, Subash C

2013-09-01

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

GC/MS analysis and characterization of 2-Hexadecen-1-ol and beta sitosterol from Schimpera arabica extract for its bioactive potential as antioxidant and antimicrobial.

PubMed

Hidayathulla, S; Shahat, A A; Ahamad, S R; Al Moqbil, A A N; Alsaid, M S; Divakar, D D

2018-05-01

We evaluated the in vitro antioxidant and antimicrobial potential of Schimpera arabica extract and fractions (2-Hexadecen-1-ol and beta sitosterol). Free radical scavenging activity was estimated by using ABTS and DPPH methods, reducing power and iron chelation was studied to investigate antioxidant potential of the extracts. Well-diffusion method was utilized to evaluate the antimicrobial activity of the extracts. Gas chromatography-mass spectroscopy analysis of the extract revealed the presence of 27 compounds. Phenolic and flavonoid contents were found in high amount (7·6-18 mg GAE, mg g -1 ; 3·2-10·8 mg catechin, mg g -1 ) in dry plant material. Among all the extracts, 2-Hexadecen-1-ol and beta sitosterol were the major constituents of crude extract and exhibited significant antioxidant potential as well antimicrobial activity; however, all other fractions also exhibited fare degree of antioxidant potential. 93% DPPH was scavenged by 100 μg ml -1 of the ethyl acetate fraction; in ABTS assay chelation was 86·2 and 88% in ferric chloride reducing power assay. Schimpera arabica is naturally present and used in food preparation in most Arabian nations. The characterization of S. arabica would provide an insight into its medicinal use as home remedial for bacterial infection and as antioxidant. Significant and comparable antimicrobial activity was demonstrated by both 2-Hexadecen-1-ol and beta sitosterol fractions. The results suggest that S. arabica contain a good amount of natural antioxidants of medicinal importance. However, further investigations are needed to characterize the further activity of 2-Hexadecen-1-ol and beta sitosterol in vivo. © 2018 The Society for Applied Microbiology.

Antibacterial, anti-inflammatory and probiotic potential of Enterococcus hirae isolated from the rumen of Bos primigenius.

PubMed

Arokiyaraj, Selvaraj; Hairul Islam, Villianur Ibrahim; Bharanidharan, R; Raveendar, Sebastian; Lee, Jinwook; Kim, Do Hyung; Oh, Young Kyoon; Kim, Eun-Kyung; Kim, Kyoung Hoon

2014-07-01

In the present study bacterial strains were isolated from the rumen fluids of Bos primigenius and investigated their in vitro probiotic properties with potent antibacterial activity and anti-inflammatory effects. 9 g positive bacterial isolates were obtained and three isolates could able to tolerate gastric conditions, high bile salt concentrations and exhibited significant bactericidal effect against the enteric pathogens Vibrio cholera, Enterococcus faecalis, Enterobacter aerogens, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi. Moreover it showed above 70% cell surface hydrophobicity, significant low-invasion ability and potential adherence capacity in Caco-2 cells when compared with the control. The proinflammatory cytokines (TNF-α) was greatly reduced in rumen bacteria treatment and ARBS-1 modulate the immune response by activating the IL-4 secretion in parallel to TNF-α suppression. The 16s rRNA gene sequence of the active isolates were identified as Enterococcus hirae (ARBS-1), Pediococcus acidilactici (ARBS-4) and Bacillus licheniformis (ARBS-7). This study revealed the probiotic bactericidal properties of E. hirae obtained from the rumen of B. primigenius with potential antibacterial and anti-inflammatory effects. Future studies with the strains may yield some novel probiotic product for livestock's.

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.

Artemisia asiatica Nakai Attenuates the Expression of Proinflammatory Mediators in Stimulated Macrophages Through Modulation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathways

PubMed Central

Kim, Eun-Kyung; Tang, Yujiao; Cha, Kwang-Suk; Choi, Heeri; Lee, Chun Bok; Yoon, Jin-Hwan; Kim, Sang Bae; Kim, Jong-Shik; Kim, Jong Moon; Han, Weon Cheol; Choi, Suck-Jun; Lee, Sangmin; Choi, Eun-Ju; Kim, Sang-Hyun

2015-01-01

Abstract The present study aimed to examine the anti-inflammatory effects and potential mechanism of action of Artemisia asiatica Nakai (A. asiatica Nakai) extract in activated murine macrophages. A. asiatica Nakai extract showed dose-dependent suppression of lipopolysaccharide (LPS)-induced nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 activity. It also showed dose-dependent inhibition of nuclear factor-κB (NF-κB) translocation from the cytosol to the nucleus and as an inhibitor of NF-κB-alpha phosphorylation. The extract's inhibitory effects were found to be mediated through NF-κB inhibition and phosphorylation of extracellular signal-regulated kinase 1/2 and p38 in LPS-stimulated J774A.1 murine macrophages, suggesting a potential mechanism for the anti-inflammatory activity of A. asiatica Nakai. To our knowledge, this is the first report of the anti-inflammatory effects of A. asiatica Nakai on J774A.1 murine macrophages; these results may help develop functional foods possessing an anti-inflammatory activity. PMID:26061361

Sesquiterpenoids from the root of Panax Ginseng protect CCl4-induced acute liver injury by anti-inflammatory and anti-oxidative capabilities in mice.

PubMed

Wang, Weidong; Wang, Shijie; Liu, Jinping; Cai, Enbo; Zhu, Hongyan; He, Zhongmei; Gao, Yugang; Li, Pingya; Zhao, Yan

2018-06-01

The oxidative stress and inflammatory response play an important role in carbon tetracholoride (CCl 4 )-induced acute liver injury. In this work, sesquiterpenoids from the root of Panax Ginseng (SPG) were prepared, and then the hepatoprotective effects of SPG against CCl 4 -induced acute liver injury were investigated and the underlying mechanism was explored in mice. All mice were divided into four groups: the control, CCl 4 and SPG (2.5 and 10 mg/kg, dissolved in soybean oil, i.g.) groups. All mice were given continuous administration for 7 days, and injected with CCl 4 (0.1 mL/10 g body weight 0.2% CCl 4 solution in soybean oil, i.p.) 1 h after the end of the administration except the control group. Mice were sacrificed 24 h post-CCl 4 injection. The results indicated that SPG significantly reduced the increasement of serum AST and ALT levels induced by CCl 4 -treatment. And the histopathological analysis revealed that SPG treated mice had normal liver architecture and no necrosis. The decreased activities of SOD, GSH and CAT, and increased MDA level were inhibited by SPG treatment. At the same time, the levels of TNF-α, IL-1β and IL-6 were significantly decreased by SPG treatment. SPG treatment also reduced the heptic protein expressions of NF-κB p65, COX-2, MAPK p38, ERK and JNK in the liver. These fingdings demonstrated that SPG exhibited strong hepatoprective effect on the CCl 4 -induced acute liver injury, which was related to anti-oxidantive and anti-inflammatory capabilities; and the anti-inflammatory effect of SPG might mediated by the NF-κB and MAPKs signaling pathways. Taken together, SPG might be a potential material for drug and functional food development against chemical hepatic injury. Copyright © 2018. Published by Elsevier Masson SAS.

Corn Silk Extract and Its Bioactive Peptide Ameliorated Lipopolysaccharide-Induced Inflammation in Mice via the Nuclear Factor-κB Signaling Pathway.

PubMed

Ho, Tin-Yun; Li, Chia-Cheng; Lo, Hsin-Yi; Chen, Feng-Yuan; Hsiang, Chien-Yun

2017-02-01

Bioactive peptides derived from foods have shown beneficial anti-inflammatory potential. Inhibitory κB kinase-β (IKKβ) plays a crucial role in the activation of nuclear factor-κB (NF-κB), a transcription factor involved in inflammation. Here we applied proteomic and bioinformatics approaches to identify anti-inflammatory peptides that target IKKβ from corn silk. Corn silk extract significantly suppressed lipopolysaccharide (LPS)-induced NF-κB activities [(1.7 ± 0.2)-fold vs (3.0 ± 0.6)-fold, p < 0.05] in cells. Trypsin hydrolysate of corn silk also suppressed LPS-induced NF-κB activities [(1.1 ± 0.3)-fold vs 3.3 ± 0.5 fold, p < 0.01]. In addition, both corn silk extract and trypsin hydrolysate significantly inhibited LPS-induced interleukin-1β (IL-1β) production by 58.3 ± 4.5 and 55.1 ± 7.4%, respectively. A novel peptide, FK2, docked into the ATP-binding pocket of IKKβ, was further identified from trypsin hydrolysis of corn silk. FK2 inhibited IKKβ activities, IκB phosphorylation, and subsequent NF-κB activation [(2.3 ± 0.4)-fold vs (5.5 ± 0.4)-fold, p < 0.001]. Moreover, FK2 significantly reduced NF-κB-driven luminescent signals in organs by 5-11-fold and suppressed LPS-induced NF-κB activities and IL-β production in tissues. In conclusion, our findings indicated that corn silk displayed anti-inflammatory abilities. In addition, we first identified an anti-inflammatory peptide FK2 from corn silk. Moreover, the anti-inflammatory effect of FK2 might be through IKKβ-NF-κB signaling pathways.

Wasabia japonica is a potential functional food to prevent colitis via inhibiting the NF-κB signaling pathway.

PubMed

Kang, Ju-Hee; Choi, Seungho; Jang, Jeong-Eun; Ramalingam, Prakash; Ko, Young Tag; Kim, Sun Yeou; Oh, Seung Hyun

2017-08-01

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Many types of drugs are used to treat IBDs, but they exhibit adverse effects such as vomiting, nausea, abdominal pain, diarrhea, etc. In order to overcome the limitations of current therapeutic drugs, scientists have searched for functional foods from natural resources. In this study, we investigated the anti-colitic effects of Wasabia japonica extract in a DSS-induced colitis model. Wasabi japonica is a plant of the Brassicaceae family that has recently been reported to exhibit properties of detoxification, anti-inflammation, and induction of apoptosis in cancer cells. In this study, we generated wasabi ethanol extract (WK) and assessed its anti-colitic effect. In addition, in order to improve delivery of the extract to the colon, WK was coated with 5% Eudragit S100 (WKE), after which the anti-colitic effects of WKE were assessed. In conclusion, WK prevented development of colitis through inhibition of the NF-kB signaling pathway and recovery of epithelial tight junctions. In addition, the anti-colitic effect of WK was enhanced by improving its delivery to the colon by coating the WK with Eudragit S100. Therefore, we suggest that wasabi can be used as a new functional food to prevent IBDs due to its anti-colitic effect.

Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation.

PubMed

Ur Rahman, Shafiq; Adhikari, Achyut; Ismail, Muhammad; Raza Shah, Muhammad; Khurram, Muhammad; Shahid, Muhammad; Ali, Farman; Haseeb, Abdul; Akbar, Fazal; Iriti, Marcello

2016-08-20

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.

Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

PubMed

Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

2015-11-15

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Maximizing dermal targeting and minimizing transdermal penetration by magnolol/honokiol methoxylation.

PubMed

Lin, Chwan-Fwu; Hwang, Tsong-Long; Al-Suwayeh, Saleh A; Huang, Yu-Ling; Hung, Yi-Yun; Fang, Jia-You

2013-03-10

Magnolol and honokiol, predominant active compounds in the family Magnoliaceae, are known to exhibit strong anti-inflammatory activities against dermal disorders. We attempted to modify the structures of magnolol and honokiol by methoxylation to optimize the skin delivery ability. Absorption of these permeants into and through the skin was performed at both an infinite dose and saturated solubility. Superoxide anion and elastase released from human neutrophils were the biomarkers used to examine anti-inflammatory potencies of these permeants. The safety of the permeants was evaluated by keratinocyte viability and in vivo bioengineering techniques. Topical magnolol and honokiol at an infinite dose (7.5 mM) showed skin accumulations of 0.22 and 0.16 nmol/mg, respectively. Methoxylation significantly enhanced their skin absorption. Deposition amounts of dimethylmagnolol and dimethylhonokiol were respectively 15- and 7-fold greater than those of magnolol and honokiol. Contrary to the skin accumulation results, the transdermal penetration across skin decreased following methoxylation. No transdermal delivery occurred for dimethylhonokiol. Skin uptake of 4'-O-methylhonokiol was 2-fold higher than that of 2-O-methylhonokiol, although they are isomers. Methoxylated permeants demonstrated selective absorption into follicles, which showed 3-5-fold higher follicular amounts compared to magnolol and honokiol. The relative order of anti-inflammatory activities was honokiol>2-O-methylmagnolol>dimethylhonokiol>magnolol. The other compounds exhibited negligible or negative responses in activated neutrophils. Magnolol and honokiol induced slight but significant keratinocyte cytotoxicity and stratum corneum disruption. Daily administration of methoxylated permeants, especially dimethylhonokiol, produced no skin irritation for up to 7 days. Methoxylated magnolol and honokiol can be efficient and safe candidates for treating inflammatory skin disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

DOR agonist (SNC-80) exhibits anti-parkinsonian effect via downregulating UPR/oxidative stress signals and inflammatory response in vivo.

PubMed

Begum M, Erfath Thanjeem; Sen, Dwaipayan

2018-06-21

The pathophysiology of Parkinson's disease exhibit imperative roles in unfolded protein response stress-induced oxidative stress and inflammation in general. Although, delta opioid receptor (DOR), has been found to represent anti-parkinsonian effect at behavioral level, its underlying mechanism remains elusive till date. In the present study the role of DOR agonist, SNC-80 and the consorted molecular mechanisms, which translates to behavioral recuperation, has been delineated. In order to mimic PD, mice were intra-peritoneally injected with MPTP, following exposure to SNC-80 and L-DOPA to elucidate amelioration of the MPTP-induced behavioral impairments. The results obtained suggest that the severity of the compromised motor functions up-regulated the UPR stress sensors: IRE-1α/Bip/CHOP, oxidative stress along with the pro-inflammatory cytokines: IL1β/IFNγ/TNFα and IL-6. These inimical factors combined, aids the persistence of the disease in MPTP intoxicated mice. Supplementation with SNC-80 significantly improved motor functions via down-regulation of the UPR stress sensors and inflammatory cytokines. Additionally, SNC-80 could upregulate Nrf-2 and Heme oxygenase-1 (HO-1) protein expression indicating their involvement in SNC-80's potential anti-oxidant function. There was also a significant reduction in protein carbonyl content indicating the positive role of SNC-80 in dampening MPTP induced oxidative stress. Concomitantly, L-DOPA also demonstrated an enhanced effect towards improvement of motor functions but did not suppress the UPR and inflammatory responses caused due to MPTP intoxication. Hence, these results suggest that SNC-80 could hold a pivotal role in replenishing motor functions essentially via regulating UPR and inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

2',4-Dihydroxy-3',4',6'-trimethoxychalcone from Chromolaena odorata possesses anti-inflammatory effects via inhibition of NF-κB and p38 MAPK in lipopolysaccharide-activated RAW 264.7 macrophages.

PubMed

Dhar, Rana; Kimseng, Rungruedee; Chokchaisiri, Ratchanaporn; Hiransai, Poonsit; Utaipan, Tanyarath; Suksamrarn, Apichart; Chunglok, Warangkana

2018-02-01

Immune dysregulation has been implicated in the pathogenesis of many diseases. Macrophages play a crucial role contributing to the onset, progression, and resolution of inflammation. Macrophage inflammatory mediators are of considerable interest as potential targets to treat inflammatory diseases. The present study was conducted to elucidate the anti-inflammatory mechanism of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1), the major chalcone isolated from Chromolaena odorata (L.) R.M.King & H.Rob, against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Cell viability, nitric oxide (NO), and proinflammatory cytokines of LPS-activated RAW 264.7 cells were measured by MTT, Griess, and ELISA assays, respectively. Cell lysates were subjected to Western blotting for investigation of protein expression. Treatment with the major chalcone 1 significantly attenuated the production of NO and proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in a dose-dependent manner. The chalcone suppressed nuclear factor-κB (NF-κB) stimulation by preventing activation of inhibitor κB kinase (IKK) α/β, degradation of inhibitor κB (IκB) α, and translocation of p65 NF-κB into the nucleus. Additionally, the chalcone markedly repressed the phosphorylation of p38 mitogen-activated protein kinase (MAPK), but no further inhibition was detected for c-Jun N-terminal activated kinases or extracellular regulated kinases. Thus, suppression of NF-κB and p38 MAPK activation may be the core mechanism underlying the anti-inflammatory activity of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1). These findings provide evidence that 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1) possesses anti-inflammatory activity via targeting proinflammatory macrophages. This anti-inflammatory chalcone is a promising compound for reducing inflammation.

A preferential p110alpha/gamma PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-kappaB-dependent manner.

PubMed

Dagia, Nilesh M; Agarwal, Gautam; Kamath, Divya V; Chetrapal-Kunwar, Anshu; Gupte, Ravindra D; Jadhav, Mahesh G; Dadarkar, Shruta S; Trivedi, Jacqueline; Kulkarni-Almeida, Asha A; Kharas, Firuza; Fonseca, Lyle C; Kumar, Sanjay; Bhonde, Mandar R

2010-04-01

A promising therapeutic approach to diminish pathological inflammation is to inhibit the increased production and/or biological activity of proinflammatory cytokines (e.g., TNF-alpha, IL-6). The production of proinflammatory cytokines is controlled at the gene level by the activity of transcription factors, such as NF-kappaB. Phosphatidylinositol 3-kinase (PI3K), a lipid kinase, is known to induce the activation of NF-kappaB. Given this, we hypothesized that inhibitors of PI3K activation would demonstrate anti-inflammatory potential. Accordingly, we studied the effects of a preferential p110alpha/gamma PI3K inhibitor (compound 8C; PIK-75) in inflammation-based assays. Mechanism-based assays utilizing human cells revealed that PIK-75-mediated inhibition of PI3K activation is associated with dramatic suppression of downstream signaling events, including AKT phosphorylation, IKK activation, and NF-kappaB transcription. Cell-based assays revealed that PIK-75 potently and dose dependently inhibits in vitro and in vivo production of TNF-alpha and IL-6, diminishes the induced expression of human endothelial cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and blocks human monocyte-endothelial cell adhesion. Most importantly, PIK-75, when administered orally in a therapeutic regimen, significantly suppresses the macroscopic and histological abnormalities associated with dextran sulfate sodium-induced murine colitis. The efficacy of PIK-75 in attenuating experimental inflammation is mediated, at least in part, due to the downregulation of pertinent inflammatory mediators in the colon. Collectively, these results provide first evidence that PIK-75 possesses anti-inflammatory potential. Given that PIK-75 is known to exhibit anti-cancer activity, the findings from this study thus reinforce the cross-therapeutic functionality of potential drugs.

Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation.

PubMed

Abdul, Latif; Abdul, Razique; Sukul, R R; Nazish, Siddiqui

2010-01-01

The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

PubMed Central

Lei, Beilei; Mace, Brian; Dawson, Hana N.; Warner, David S.; Laskowitz, Daniel T.; James, Michael L.

2014-01-01

Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone’s effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury. PMID:25080336

A novel dissociative steroid VBP15 reduces MUC5AC gene expression in airway epithelial cells but lacks the GRE mediated transcriptional properties of dexamethasone.

PubMed

Garvin, Lindsay M; Chen, Yajun; Damsker, Jesse M; Rose, Mary C

2016-06-01

Overproduction of secretory mucins contributes to morbidity/mortality in inflammatory lung diseases. Inflammatory mediators directly increase expression of mucin genes, but few drugs have been shown to directly repress mucin gene expression. IL-1β upregulates the MUC5AC mucin gene in part via the transcription factors NFκB while the glucocorticoid Dexamethasone (Dex) transcriptionally represses MUC5AC expression by Dex-activated GR binding to two GRE cis-sites in the MUC5AC promoter in lung epithelial cells. VBP compounds (ReveraGen BioPharma) maintain anti-inflammatory activity through inhibition of NFκB but exhibit reduced GRE-mediated transcriptional properties associated with adverse side-effects and thus have potential to minimize harmful side effects of long-term steroid therapy in inflammatory lung diseases. We investigated VBP15 efficacy as an anti-mucin agent in two types of airway epithelial cells and analyzed the transcription factor activity and promoter binding associated with VBP15-induced MUC5AC repression. VBP15 reduced MUC5AC mRNA abundance in a dose- and time-dependent manner similar to Dex in the presence or absence of IL-1β in A549 and differentiated human bronchial epithelial cells. Repression was abrogated in the presence of RU486, demonstrating a requirement for GR in the VBP15-induced repression of MUC5AC. Inhibition of NFκB activity resulted in reduced baseline expression of MUC5AC indicating that constitutive activity maintains MUC5AC production. Chromatin immunoprecipitation analysis demonstrated lack of GR and of p65 (NFκB) binding to composite GRE domains in the MUC5AC promoter following VBP15 exposure of cells, in contrast to Dex. These data demonstrate that VBP15 is a novel anti-mucin agent that mediates the reduction of MUC5AC gene expression differently than the classical glucocorticoid, Dex. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory effects of Zea mays L. husk extracts.

PubMed

Roh, Kyung-Baeg; Kim, Hyoyoung; Shin, Seungwoo; Kim, Young-Soo; Lee, Jung-A; Kim, Mi Ok; Jung, Eunsun; Lee, Jongsung; Park, Deokhoon

2016-08-19

Zea mays L. (Z. mays) has been used for human consumption in the various forms of meal, cooking oil, thickener in sauces and puddings, sweetener in processed food and beverage products, bio-disel. However, especially, in case of husk extract of Z. mays, little is known about its anti-inflammatory effects. Therefore, in this study, the anti-inflammatory effects of Z. mays husk extract (ZMHE) and its mechanisms of action were investigated. The husks of Z. Mays were harvested in kangwondo, Korea. To assess the anti-inflammatory activities of ZMHE, we examined effects of ZMHE on nitric oxide (NO) production, and release of soluble intercellular adhesion molecule-1 (sICAM-1) and eotaxin-1. The expression level of inducible nitric oxide synthase (iNOS) gene was also determined by Western blot and luciferase reporter assays. To determine its mechanisms of action, a luciferase reporter assay for nuclear factor kappa B (NF-kB) and activator protein-1 (AP-1) was introduced. ZMHE inhibited lipopolysaccharide (LPS)-induced production of NO in RAW264.7 cells. In addition, expression of iNOS gene was reduced, as confirmed by Western blot and luciferase reporter assays. Effects of ZMHE on the AP-1 and NF-kB promoters were examined to elucidate the mechanism of its anti-inflammatory activity. Activation of AP-1 and NF-kB promoters induced by LPS was significantly reduced by ZMHE treatment. In addition, LPS-induced production of sICAM-1 and IL-4-induced production of eotaxin-1 were all reduced by ZMHE. Our results indicate that ZMHE has anti-inflammatory effects by downregulating the expression of iNOS gene and its downregulation is mediated by inhibiting NF-kB and AP-1 signaling.

Anti-inflammatory, gastroprotective, and cytotoxic effects of Sideritis scardica extracts.

PubMed

Tadić, Vanja M; Jeremic, Ivica; Dobric, Silva; Isakovic, Aleksandra; Markovic, Ivanka; Trajkovic, Vladimir; Bojovic, Dragica; Arsic, Ivana

2012-03-01

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity. © Georg Thieme Verlag KG Stuttgart · New York.

Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.

PubMed

Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

2016-10-10

The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

Green, unexpected synthesis of bis-coumarin derivatives as potent anti-bacterial and anti-inflammatory agents.

PubMed

Chougala, Bahubali M; Samundeeswari, S; Holiyachi, Megharaja; Naik, Nirmala S; Shastri, Lokesh A; Dodamani, Suneel; Jalalpure, Sunil; Dixit, Sheshagiri R; Joshi, Shrinivas D; Sunagar, Vinay A

2018-01-01

A green and efficient protocol has been developed and a series of coumarin based pyrano[3,2-c]chromene derivatives (2) have been synthesized using multi-component reaction (MCR) approach. Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (3) and C 4 -C 4 chromenes (5) have been isolated instead of expected product 4 by the reaction of compound (2) in formic acid at 90 °C for about 4-5 h and at 130 °C for about 8-10 h respectively. Further, C 4 -C 4 chromenes (5) formation was confirmed by intramolecular cyclization of compounds (3). These compounds were screened for their biological activities and most of them exhibited promising antibacterial activity. The anti-inflammatory assay was evaluated against HRBC membrane stabilization method and the compounds exhibit excellent anti-inflammatory activity. Molecular docking study has been performed for all the synthesized compounds with Klebsiella pneumoni aeacetolactate synthase and results obtained are quite promising. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hepatoprotective effect of grape seed oil against carbon tetrachloride induced oxidative stress in liver of γ-irradiated rat.

PubMed

Ismail, Amel F M; Salem, Asmaa A M; Eassawy, Mamdouh M T

2016-07-01

Carbon tetrachloride (CCl4) and ionizing radiation are well known environmental pollutants that generate free radicals and induce oxidative stress. The liver is the primary and major target organ responsible for the metabolism of drugs, toxic chemicals and affected by irradiation. This study investigated the effect of grape seed oil (GSO) on acute liver injury induced by carbon tetrachloride (CCl4) in γ-irradiated rats (7Gy). CCl4-intoxicated rats exhibited an elevation of ALT, AST activities, IL-6 and TNF-α level in the serum. Further, the levels of MDA, NO, NF-κB and the gene expression of CYP2E1, iNOS and Caspase-3 were increased, and SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Furthermore, silent information regulator protein 1 (SIRT1) gene expression was markedly down-regulated. Additionally, alterations of the trace elements; copper, manganese, zinc and DNA fragmentation was observed in the hepatic tissues of the intoxicated group. These effects were augmented in CCl4-intoxicated-γ-irradiated rats. However, the administration of GSO ameliorated these parameters. GSO exhibit protective effects on CCl4 induced acute liver injury in γ-irradiated rats that could be attributed to its potent antioxidant, anti-inflammatory and anti-apoptotic activities. The induction of the antioxidant enzymes activities, down-regulation of the CYP2E1, iNOS, Caspase-3 and NF-κB expression, up-regulation of the trace elements concentration levels and activation of SIRT1 gene expression are responsible for the improvement of the antioxidant and anti-inflammatory status in the hepatic tissues and could be claimed to be the hepatoprotective mechanism of GSO. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammatory effects of ethanolic extract from Sargassum horneri (Turner) C. Agardh on lipopolysaccharide-stimulated macrophage activation via NF-κB pathway regulation.

PubMed

Kim, Mi Eun; Jung, Yun Chan; Jung, Inae; Lee, Hee-Woo; Youn, Hwa-Young; Lee, Jun Sik

2015-01-01

Inflammation is major symptom of the innate immune response by infection of microbes. Macrophages, one of immune response related cells, play a role in inflammatory response. Recent studies reported that various natural products can regulate the activation of immune cells such as macrophage. Sargassum horneri (Turner) C. Agardh is one of brown algae. Recently, various seaweeds including brown algae have antioxidant and anti-inflammatory effects. However, anti-inflammatory effects of Sargassum horneri (Turner) C. Agardh are still unknown. In this study, we investigated anti-inflammatory effects of ethanolic extract of Sargassum horneri (Turner) C. Agardh (ESH) on RAW 264.7 murine macrophage cell line. The ESH was extracted from dried Sargassum horneri (Turner) C. Agardh with 70% ethanol and then lyophilized at -40 °C. ESH was not cytotoxic to RAW 264.7, and nitric oxide (NO) production induced by LPS-stimulated macrophage activation was significantly decreased by the addition of 200 μg/mL of ESH. Moreover, ESH treatment reduced mRNA level of cytokines, including IL-1β, and pro-inflammatory genes such as iNOS and COX-2 in LPS-stimulated macrophage activation in a dose-dependent manner. ESH was found to elicit anti-inflammatory effects by inhibiting ERK, p-p38 and NF-κB phosphorylation. In addition, ESH inhibited the release of IL-1β in LPS-stimulated macrophages. These results suggest that ESH elicits anti-inflammatory effects on LPS-stimulated macrophage activation via the inhibition of ERK, p-p38, NF-κB, and pro-inflammatory gene expression.

Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

PubMed Central

2011-01-01

Background Circulating levels of novel long-chain hydroxy fatty acids (called GTAs) were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC), independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation. Methods GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive) and depleted (GTA-negative) fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined. Results Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2. Conclusions Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC. PMID:21586136

Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition

PubMed Central

Lu, Li; Qin, Aiping; Huang, Hongbiao; Zhou, Ping; Zhang, Chuanyin; Liu, Ningning; Li, Shujue; Wen, Guanmei; Zhang, Change; Dong, Weihua; Wang, Xuejun; Dou, Q. Ping; Liu, Jinbao

2012-01-01

Shikonin, extracted from medicinal Chinese herb (Lithospermum erythrorhizo), was reported to exert anti-inflammatory and anti-cancer effects both in vitro and in vivo. We have found that proteasome was a molecular target of shikonin in tumor cells, but whether shikonin targets macrophage proteasome needs to be investigated. In the current study, we report that shikonin inhibited inflammation in mouse models as efficiently as dexamethasone. Shikonin at 4 μM reduced the Lipopolysaccharides (LPS)-mediated TNFα release in rat primary macrophage cultures, and blocked the translocation of p65-NF-κB from the cytoplasm to the nucleus, associated with decreased proteasomal activity. Consistently, shikonin accumulated IκB-α, an inhibitor of NF-κB, and ubiquitinated proteins in rat primary macrophage cultures, demonstrating that the proteasome is a target of shikonin under inflammatory conditions. Shikonin also induced macrophage cell apoptosis and cell death. These results demonstrate for the first time that proteasome inhibition by shikonin contributes to its anti-inflammatory effect. The novel finding about macrophage proteasome as a target of shikonin suggests that this medicinal compound has great potential to be developed into an anti-inflammatory agent. PMID:21392503

Anti-inflammatory effect of ethanolic extract of spine, skin and rind of Jack fruit peel - A comparative study.

PubMed

Meera, M; Ruckmani, A; Saravanan, R; Lakshmipathy Prabhu, R

2017-10-09

The present study was conducted to identify the chemical constituents and evaluate the anti-inflammatory activity of crude ethanolic extracts of spine, skin and rind of jack fruit (Artocarpus heterophyllus) peel. Polyphenol and flavonoid contents were assessed using Folin's Ciocalteu reagent and aluminium chloride methods which revealed 316, 355 and 382 mg tannic acid equivalent/g of polyphenol and 96.7, 131.6 and 164.6 mg quercetin equivalent/g of flavonoid in spine, skin and rind, respectively. Anti-inflammatory activity of all three extracts was comparable to diclofenac in vitro and in vivo studies. Skin exhibited maximum anti-inflammatory activity, rind had preferential inhibition on Cyclooxygenase-2 and spine and skin inhibited both Cyclooxygenase-1 and 2 in vitro.

Novel enzyme formulations for improved pharmacokinetic properties and anti-inflammatory efficacies.

PubMed

Yang, Lan; Yan, Shenglei; Zhang, Yonghong; Hu, Xueyuan; Guo, Qi; Yuan, Yuming; Zhang, Jingqing

2018-02-15

Anti-inflammatory enzymes promote the dissolution and excretion of sticky phlegm, clean the wound surface and accelerate drug diffusion to the lesion. They play important roles in treating different types of inflammation and pain. Currently, various formulations of anti-inflammatory enzymes are successfully prepared to improve the enzymatic characteristics, pharmacokinetic properties and anti-inflammatory efficacies. The work was performed by systematically searching all available literature. An overall summary of current research about various anti-inflammatory enzymes and their novel formulations is presented. The original and improved enzymatic characteristics, pharmacokinetic properties, action mechanisms, clinical information, storage and shelf life, treatment efficacies of anti-inflammatory enzymes and their different formulations are summarized. The influencing factors such as enzyme type, source, excipient, pharmaceutical technique, administration route and dosage are analyzed. The combined application of enzymes and other drugs are included in this paper. Anti-inflammatory enzymes were widely applied in treating different types of inflammation and diseases with accompanying edema. Their novel formulations increased enzymatic stabilities, improved pharmacokinetic properties, provided different administration routes, and enhanced anti-inflammatory efficacies of anti-inflammatory enzymes but decreased side effects and toxicity. Novel enzyme formulations improve and expand the usage of anti-inflammatory enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling

PubMed Central

Kim, Jaeyong; Kim, Heesook; Choi, Hakjoon; Jo, Ara; Kang, Huwon; Yun, Hyojeong; Im, Sojeong; Choi, Chulyung

2018-01-01

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E2 in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation. PMID:29361789

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling.

PubMed

Kim, Jaeyong; Kim, Heesook; Choi, Hakjoon; Jo, Ara; Kang, Huwon; Yun, Hyojeong; Im, Sojeong; Choi, Chulyung

2018-01-22

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E₂ in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation.

Adherent Human Alveolar Macrophages Exhibit a Transient Pro-Inflammatory Profile That Confounds Responses to Innate Immune Stimulation

PubMed Central

Tomlinson, Gillian S.; Booth, Helen; Petit, Sarah J.; Potton, Elspeth; Towers, Greg J.; Miller, Robert F.; Chain, Benjamin M.; Noursadeghi, Mahdad

2012-01-01

Alveolar macrophages (AM) are thought to have a key role in the immunopathogenesis of respiratory diseases. We sought to test the hypothesis that human AM exhibit an anti-inflammatory bias by making genome-wide comparisons with monocyte derived macrophages (MDM). Adherent AM obtained by bronchoalveolar lavage of patients under investigation for haemoptysis, but found to have no respiratory pathology, were compared to MDM from healthy volunteers by whole genome transcriptional profiling before and after innate immune stimulation. We found that freshly isolated AM exhibited a marked pro-inflammatory transcriptional signature. High levels of basal pro-inflammatory gene expression gave the impression of attenuated responses to lipopolysaccharide (LPS) and the RNA analogue, poly IC, but in rested cells pro-inflammatory gene expression declined and transcriptional responsiveness to these stimuli was restored. In comparison to MDM, both freshly isolated and rested AM showed upregulation of MHC class II molecules. In most experimental paradigms ex vivo adherent AM are used immediately after isolation. Therefore, the confounding effects of their pro-inflammatory profile at baseline need careful consideration. Moreover, despite the prevailing view that AM have an anti-inflammatory bias, our data clearly show that they can adopt a striking pro-inflammatory phenotype, and may have greater capacity for presentation of exogenous antigens than MDM. PMID:22768282

Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation.

PubMed

Marwick, John A; Mills, Ross; Kay, Oliver; Michail, Kyriakos; Stephen, Jillian; Rossi, Adriano G; Dransfield, Ian; Hirani, Nikhil

2018-06-04

Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid and sustained suppression of NF-κB signalling in the macrophage through a unique regulatory relationship which is independent of apoptosis. The reduction of macrophage NF-κB activation occurs through a blockade in transforming growth factor β-activated kinase 1 (TAK1) and IKKβ activation. As a consequence, NF-κB (p65) phosphorylation is reduced, its translocation to the nucleus is inhibited and NF-κB-mediated inflammatory cytokine transcription is suppressed. Gene Set Enrichment Analysis reveals that this suppression of NF-κB activation is not restricted to post-translational modifications of the canonical NF-κB pathway, but is also imprinted at the transcriptional level. Thus neutrophils exert a sustained anti-inflammatory phenotypic reprogramming of the macrophage, which is reflected by the sustained reduction in the release of pro- but not anti- inflammatory cytokines from the macrophage. Together, our findings identify a novel apoptosis-independent mechanism by which neutrophils regulate the mediator profile and reprogramming of monocytes/macrophages, representing an important nodal point for inflammatory control.

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.

Nuclear Factor-κB Inhibitors as Potential Novel Anti-Inflammatory Agents for the Treatment of Immune Glomerulonephritis

PubMed Central

López-Franco, Oscar; Suzuki, Yusuke; Sanjuán, Guillermo; Blanco, Julia; Hernández-Vargas, Purificación; Yo, Yoshikage; Kopp, Jeffrey; Egido, Jesús; Gómez-Guerrero, Carmen

2002-01-01

Nuclear factor (NF)-κB regulates several genes implicated in the inflammatory response and represents an interesting therapeutic target. We examined the effects of gliotoxin (a fungal metabolite) and parthenolide (a plant extract), which possess anti-inflammatory activities in vitro, on the progression of experimental glomerulonephritis. In the anti-Thy 1.1 rat model, gliotoxin (75 μg/rat/day, 10 days, n = 18 rats) markedly reduced proteinuria, glomerular lesions, and monocyte infiltration. In anti-mesangial cell nephritis in mice, parthenolide (70 μg/mouse/day, 7 days, n = 17 mice) significantly decreased proteinuria, hematuria, and glomerular proliferation. NF-κB activity, localized in glomerular and tubular cells, was attenuated by either gliotoxin or parthenolide, in association with diminished renal expression of monocyte chemoattractant protein-1 and inducible nitric oxide synthase. In cultured mesangial cells and monocytes, gliotoxin and parthenolide inhibited NF-κB activation and expression of inflammatory genes induced by lipopolysaccharide and cytokines, by blocking the phosphorylation/degradation of the IκBα subunit. In summary, gliotoxin and parthenolide prevent proteinuria and renal lesions by inhibiting NF-κB activation and expression of regulated genes. This may represent a novel approach for the treatment of immune and inflammatory renal diseases. PMID:12368222

Assessment of anti-inflammatory, antinociceptive, immunomodulatory, and antioxidant activities of Cajanus cajan L. seeds cultivated in Egypt and its phytochemical composition.

PubMed

Hassan, Emad M; Matloub, Azza A; Aboutabl, Mona E; Ibrahim, Nabaweya A; Mohamed, Samy M

2016-08-01

Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine. The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied. Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400 mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated. Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, β-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-β-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-β-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400 mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400 mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC50) value: 9.07 μg/ml).

Targeting peripheral blood pro-inflammatory cytotoxic lymphocytes by inhibiting CD137 expression: novel potential treatment for COPD.

PubMed

Hodge, Greg; Holmes, Mark; Jersmann, Hubertus; Reynolds, Paul N; Hodge, Sandra

2014-05-15

We have shown that chronic obstructive pulmonary disease (COPD) is associated with increased production of pro-inflammatory cytokines and the cytotoxic mediator, granzyme B by peripheral blood steroid resistant CD28nullCD137 + CD8+ T cells and granzyme B by NKT-like and NK cells. We hypothesized that we could target these pro-inflammatory/cytotoxic lymphocytes by inhibiting co-stimulation through CD137. Isolated PBMC from patients with COPD and healthy controls were stimulated with phytohaemagglutinin (PHA) ± blocking anti-CD137 ± 10(-6) M methylprednislone (MP) (±stimulatory anti-CD137 ± control antibodies). Pro-inflammatory cytokine profiles and expression of granzyme B, by T, NKT-like CD28 ± subsets and NK cells were determined using flow cytometry. There was a significant decrease in the percentage of T, NKT-like subsets and NK cells producing IFNγ, TNFα and granzyme B in all subjects in the presence of anti-CD137 blocking antibody compared with PHA alone (eg, 60% decrease in CD8 + granzyme B + cells) or MP. Stimulatory anti-CD137 was associated with an increase in the percentage of pro-inflammatory/cytotoxic cells. The inhibitory effect of anti-CD137 on IFNγ, TNFα and granzyme B production by CD28null cells was greater than by CD28+ cells. Blocking CD137 expression is associated with downregulation of IFNγ, TNFα and granzyme B by CD8+ T and NKT-like and NK cells. Targeting CD137 may have novel therapeutic implications for patients with COPD.

The beneficial health aspects of sea buckthorn (Elaeagnus rhamnoides (L.) A.Nelson) oil.

PubMed

Olas, Beata

2018-03-01

Plant oils are known to have biological activity. This review paper summarizes the current knowledge of the composition of sea buckthorn (Elaeagnus rhamnoides (L.) A.Nelson) seed and pulp oil and its beneficial health aspects. In vitro and in vivo studies on humans and animals have found sea buckthorn oil to have a variety of beneficial properties to human health, and indicate that it may be a valuable component of human and animal nutrition. Various bioactive substances are present in all parts of sea buckthorn, and these are used traditionally as raw material for health foods and as nutritional supplements. The oil, berries, leaves and bark have medicinal properties, and the fruits have a unique taste; these parts can be processed to make oil, juice, jam, jellies and candies, as well as alcoholic and non-alcoholic beverages. Sea buckthorn oil may be extracted from the seed or the pulp. The mature seeds contain 8-20% oil and the dried fruit pulp about 20-25%, while the fruit residue contains about 15-20% oil after juice extraction. These oils have high concentrations of lipophilic constituents, most commonly unsaturated fatty acids (UFAs), phytosterols and vitamins A and E. These components have a multifunctional effect on human health, with the fatty acids playing an important function in modifying cerebrovascular and cardiovascular disorders. The oil also has anti-oxidant, anti-inflammatory and anti-depressive properties. Sea buckthorn is a unique plant. Its beneficial properties against cardiovascular disorders have been attributed to its high UFA content and range of phytosterols, especially beta-sitosterol. However, its different action on the human organism remain unclear, and further well-controlled, high-quality experiments with human subjects are required to determine the prophylactic and therapeutic doses of sea buckthorn oil for use in clinical studies. Additional studies are also needed to understand the action by which the oil exerts its beneficial properties, i.e. its cardioprotective and anti-cancer activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-Inflammatory Effects of a Mytilus coruscus α-d-Glucan (MP-A) in Activated Macrophage Cells via TLR4/NF-κB/MAPK Pathway Inhibition

PubMed Central

Liu, Fuyan; Zhang, Xiaofeng; Li, Yuqiu; Chen, Qixin; Liu, Fei; Zhu, Xiqiang; Mei, Li; Song, Xinlei; Liu, Xia; Song, Zhigang; Zhang, Jinhua; Zhang, Wen; Ling, Peixue

2017-01-01

The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction. PMID:28930149

Anti-Inflammatory Effects of a Mytilus coruscus α-d-Glucan (MP-A) in Activated Macrophage Cells via TLR4/NF-κB/MAPK Pathway Inhibition.

PubMed

Liu, Fuyan; Zhang, Xiaofeng; Li, Yuqiu; Chen, Qixin; Liu, Fei; Zhu, Xiqiang; Mei, Li; Song, Xinlei; Liu, Xia; Song, Zhigang; Zhang, Jinhua; Zhang, Wen; Ling, Peixue; Wang, Fengshan

2017-09-20

The hard-shelled mussel ( Mytilus coruscus ) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus , and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction.

Anti-inflammatory effects of shea butter through inhibition of iNOS, COX-2, and cytokines via the Nf-κB pathway in LPS-activated J774 macrophage cells.

PubMed

Verma, Nandini; Chakrabarti, Rina; Das, Rakha H; Gautam, Hemant K

2012-01-12

Shea butter is traditionally used in Africa for its anti-inflammatory and analgesic effects. In this study we explored the anti-inflammatory activities of the methanolic extract of shea butter (SBE) using lipopolysaccharide (LPS)-induced murine macrophage cell line J774. It was observed that SBE significantly reduced the levels of LPS-induced nitric oxide, Tumor necrosis factor-α (TNF-α), interleukins, 1β (IL-1β), and -12 (IL-12) in the culture supernatants in a dose dependent manner. Expression of pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were also inhibited by SBE. These anti-inflammatory effects were due to an inhibitory action of SBE on LPS-induced iNOS, COX-2, TNF-α, IL-1β, and IL-12 mRNA expressions. Moreover, SBE efficiently suppressed IκB phosphorylation and NF-κB nuclear translocation induced by LPS. These findings explain the molecular bases of shea butter's bioactivity against various inflammatory conditions and substantiate it as a latent source of novel therapeutic agents.

6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ.

PubMed

Han, Qinghe; Yuan, Qinghai; Meng, Xiaolin; Huo, Junyuan; Bao, Yuxin; Xie, Guanghong

2017-06-27

6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been known to have anti-tumor and anti-inflammatory effects. However, the anti-inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2 microglia remains largely unknown. In this study, we evaluated the anti-inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was administrated 1 h before LPS treatment. The production of inflammatory mediators were detected by ELISA. The expression of NF-κB and PPAR-γ were detected by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 production in a concentration dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-κB activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. In addition, 6-Shogaol could increase the expression of PPAR-γ. Moreover, inhibition of PPAR-γ by GW9662 could prevent the inhibition of 6-Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol inhibits LPS-induced inflammation by activating PPAR-γ.

Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals.

PubMed

Zakaria, Z A; Raden Mohd Nor, R N S; Hanan Kumar, G; Abdul Ghani, Z D F; Sulaiman, M R; Rathna Devi, G; Mat Jais, A M; Somchit, M N; Fatimah, C A

2006-12-01

The present study was carried out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of the aqueous extract of Melastoma malabathricum leaves in experimental animals. The antinociceptive activity was measured using abdominal constriction, hot-plate, and formalin tests, whereas the anti-inflammatory and antipyretic activities were measured using carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, which was obtained after soaking the air-dried leaves in distilled water for 72 h and then preparing in concentrations of 10%, 50%, and 100% (v/v), was administered subcutaneously 30 min prior to subjection to the above mentioned assays. At all concentrations tested, the extract was found to exhibit significant (P < 0.05) antinociceptive, anti-inflammatory, and antipyretic activities in a concentration-independent manner. Our findings that the aqueous extract of M. malabathricum possesses antinociceptive, anti-inflammatory, and antipyretic activities supports previous claims on its traditional uses to treat various ailments.

Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper (Capsicum annuum L.).

PubMed

Hernández-Ortega, Marcela; Ortiz-Moreno, Alicia; Hernández-Navarro, María Dolores; Chamorro-Cevallos, Germán; Dorantes-Alvarez, Lidia; Necoechea-Mondragón, Hugo

2012-01-01

Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4 μg/g, pasilla 2933 ± 1 μg/g, and ancho 1437 ± 6 μg/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH(+) cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80 mg/kg and induced central analgesia at 80 mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief.

Antioxidant, Antinociceptive, and Anti-Inflammatory Effects of Carotenoids Extracted from Dried Pepper (Capsicum annuum L.)

PubMed Central

Hernández-Ortega, Marcela; Ortiz-Moreno, Alicia; Hernández-Navarro, María Dolores; Chamorro-Cevallos, Germán; Dorantes-Alvarez, Lidia; Necoechea-Mondragón, Hugo

2012-01-01

Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4 μg/g, pasilla 2933 ± 1 μg/g, and ancho 1437 ± 6 μg/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH+ cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80 mg/kg and induced central analgesia at 80 mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief. PMID:23091348

Indolyl-isoxazolidines attenuate LPS-stimulated pro-inflammatory cytokines and increase survival in a mouse model of sepsis: Identification of potent lead.

PubMed

Singh, Gagandeep; Singh, Gurjit; Bhatti, Rajbir; Gupta, Mehak; Kumar, Ajay; Sharma, Ankita; Singh Ishar, Mohan Paul

2018-06-10

A library of indolyl-isoxazolidines (6-9) has been synthesized by regio- and stereoselective microwave irradiated 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (2') with variedly substituted dipolarophiles (3'-5') and screened for their anti-inflammatory activities through inhibition of pro-inflammatory cytokines such as TNF-α and IL-6. Amongst the evaluated compounds (6-9), bicyclic isoxazolidine (9a) was found to exhibit significant inhibitory potential against LPS induced human IL-6 and TNF-α in THP-1 cells. Compound 9a was further assessed for in vivo analgesic and anti-inflammatory activities via acetic acid induced writhing and carrageenan induced paw edema models in mice, respectively. The results showed that compound possesses potent anti-inflammatory-analgesic activity comparable to indomethacin and did not show toxicity up to a 2000 mg kg -1 dose as evidenced by histopathological studies. Consequently, the most active compound 9a was also evaluated against LPS-induced septic death and exhibited a significant protection in in vivo mouse model. Taken all together, the results suggest that the compound 9a is able to attenuate pro-inflammatory cytokines such as IL-6 and TNF-α; accelerate resolution of inflammation, and also increased survival rate of septic mice. Therefore, these "lead" isoxazolidines can be used as promising candidate for further analgesic/anti-inflammatory drug design and development. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

PubMed Central

Keeble, J E; Moore, P K

2002-01-01

This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

Bioactive Steroids with Methyl Ester Group in the Side Chain from a Reef Soft Coral Sinularia brassica Cultured in a Tank.

PubMed

Huang, Chiung-Yao; Su, Jui-Hsin; Liaw, Chih-Chuang; Sung, Ping-Jyun; Chiang, Pei-Lun; Hwang, Tsong-Long; Dai, Chang-Feng; Sheu, Jyh-Horng

2017-09-01

A c ontinuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica , which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A-D (1-4) for the first time. In particular, 1 possesses a β-D-xylopyranose. The structures of the new compounds were elucidated on the basis of spectroscopic analyses. The cytotoxicities of compounds 1-4 against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of these new compounds 1-4 were also evaluated by measuring their ability to suppress superoxide anion generation and elastase release in N -formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils. Compounds 2 and 3 were shown to exhibit significant cytotoxicity, and compounds 3 and 4 were also found to display attracting anti-inflammatory activities.

Synthesis and anti-inflammatory activity of some benzofuran and benzopyran-4-one derivatives.

PubMed

Ragab, Fatma Abd El-Fattah; Eid, Nahed Mahmoud; Hassan, Ghaneya Sayed; Nissan, Yassin Mohammed

2012-01-01

New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b, 6-(aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones 16a-c and 6-[6-aryl-2-thioxo-2,5-dihydropyrimidin-4-yl]-4H-chromen-4-ones 17a-c were synthesized. Anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema model in rats and prostaglandin E(2) (PGE(2)) synthesis inhibition activity. Some of the tested compounds revealed comparable activity with less ulcerogenic effect than Diclofenac at a dose 100 mg/kg. All the synthesized compounds were docked on the active site of cyclooxygenase-2 (COX-2) enzyme and most of them showed good interactions with the amino acids of the active site comparable to the interactions exhibited by Diclofenac.

Transcriptome Analysis of the Carmine Spider Mite, Tetranychus cinnabarinus (Boisduval, 1867) (Acari: Tetranychidae), and Its Response to β-Sitosterol

PubMed Central

Bu, Chunya; Li, Jinling; Wang, Xiao-Qin; Shi, Guanglu; Peng, Bo; Han, Jingyu; Gao, Pin; Wang, Younian

2015-01-01

Tetranychus cinnabarinus (Acari: Tetranychidae) is a worldwide polyphagous agricultural pest that has the title of resistance champion among arthropods. We reported previously the identification of the acaricidal compound β-sitosterol from Mentha piperita and Inula japonica. However, the acaricidal mechanism of β-sitosterol is unclear. Due to the limited genetic research carried out, we de novo assembled the transcriptome of T. cinnabarinus using Illumina sequencing and conducted a differential expression analysis of control and β-sitosterol-treated mites. In total, we obtained >5.4 G high-quality bases for each sample with unprecedented sequencing depth and assembled them into 22,941 unigenes. We identified 617 xenobiotic metabolism-related genes involved in detoxification, binding, and transporting of xenobiotics. A highly expanded xenobiotic metabolic system was found in mites. T. cinnabarinus detoxification genes—including carboxyl/cholinesterase and ABC transporter class C—were upregulated after β-sitosterol treatment. Defense-related proteins, such as Toll-like receptor, legumain, and serine proteases, were also activated. Furthermore, other important genes—such as the chloride channel protein, cytochrome b, carboxypeptidase, peritrophic membrane chitin binding protein, and calphostin—may also play important roles in mites' response to β-sitosterol. Our results demonstrate that high-throughput-omics tool facilitates identification of xenobiotic metabolism-related genes and illustration of the acaricidal mechanisms of β-sitosterol. PMID:26078964

5,7-Dihydroxyflavone Analogues May Regulate Lipopolysaccharide-Induced Inflammatory Responses by Suppressing IκBα-Linked Akt and ERK5 Phosphorylation in RAW 264.7 Macrophages

PubMed Central

Shimizu, Kazue; Koketsu, Mamoru; Ninomiya, Masayuki; Sato, Daisuke; Suzuki, Takashi; Hayakawa, Satoshi

2017-01-01

We studied the anti-inflammatory activity of twelve 5,7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1) and 4′-methoxytricetin (9) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1β and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of IκBα, leading to the activation of NFκB. Phosphorylation of Akt and ERK5 (upstream of NFκB) by LPS stimulation was significantly regulated by 1 and 9, as well as by BIX 02189 and LY 294002, which are phosphorylation inhibitors of ERK5 and Akt, respectively. The results suggest that compounds 1 and 9 may suppress the levels of iNOS and COX2 by regulating phosphorylation of Akt, ERK5, and IκBα and thus NFκB-related signaling pathways, resulting in anti-inflammatory effects in the cells. Because 1 and 9 showed low cytotoxicity and regulated both PGE2 and NO production caused by inflammatory responses, they may hold promise as natural anti-inflammatory agents. PMID:28539967

Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

PubMed

Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

2005-01-01

As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects.

Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free radical scavenging effects of Rumex nepalensis.

PubMed

Gautam, Raju; Karkhile, Kailas V; Bhutani, Kamlesh K; Jachak, Sanjay M

2010-10-01

Evaluation of the topical anti-inflammatory activity of chloroform and ethyl acetate extracts of RUMEX NEPALENSIS roots in a TPA-induced acute inflammation mouse model demonstrated a significant reduction in ear edema. The extracts were further tested on purified enzymes for COX-1 and COX-2 inhibition to elucidate their mechanism of action, and a strong inhibition was observed. Six anthraquinones and two naphthalene derivatives were isolated from the ethyl acetate extract. Among the isolated compounds, emodin was found to be a potent inhibitor with slight selectivity towards COX-2, and nepodin exhibited selectivity towards COX-1. Emodin, endocrocin, and nepodin also exhibited significant topical anti-inflammatory activity in mice. Interestingly, nepodin showed better radical scavenging activity than trolox and ascorbic acid against DPPH and ABTS radicals. The strong radical scavenging activity of chloroform and ethyl acetate extracts could be explained by the presence of nepodin as well as by the high phenolic content of the ethyl acetate extract. Thus, the anti-inflammatory effect of R. NEPALENSIS roots was assumed to be mediated through COX inhibition by anthraquinones and naphthalene derivatives and through the radical scavenging activities of naphthalene derivatives. © Georg Thieme Verlag KG Stuttgart · New York.

Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities.

PubMed

Bansal, Yogita; Silakari, Om

2014-11-01

Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole-non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1-10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC50 value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski's parameters suggested the compounds to be bear drug like properties.

Anti-inflammatory phenanthrene derivatives from stems of Dendrobium denneanum.

PubMed

Lin, Yuan; Wang, Fei; Yang, Li-Juan; Chun, Ze; Bao, Jin-Ku; Zhang, Guo-Lin

2013-11-01

Cultivated Dendrobium denneanum has been substituted for other endangered Dendrobium species in recent years, but there have been few studies regarding either its chemical constituents or pharmacological effects. In this study, three phenanthrene glycosides, three 9,10-dihydrophenanthrenes, two 9,10-dihydrophenanthrenes glycosides, and four known phenanthrene derivatives, were isolated from the stems of D. denneanum. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Ten compounds were found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells with IC50 values of 0.7-41.5 μM, and exhibited no cytotoxicity in RAW264.7, HeLa, or HepG2 cells. Additionally, it was found that 2,5-dihydroxy-4-methoxy-phenanthrene 2-O-β-d-glucopyranoside, and 5-methoxy-2,4,7,9S-tetrahydroxy-9,10-dihydrophenanthrene suppressed LPS-induced expression of inducible NO synthase (iNOS) inhibited phosphorylation of p38, JNK as well as mitogen-activated protein kinase (MAPK), and inhibitory kappa B-α (IκBα). This indicated that both compounds exert anti-inflammatory effects by inhibiting MAPKs and nuclear factor κB (NF-κB) pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anti-inflammatory effect of a Nuphar lutea partially purified leaf extract in murine models of septic shock.

PubMed

Ozer, J; Levi, T; Golan-Goldhirsh, A; Gopas, J

2015-02-23

Various plant organs of Nuphar lutea (L.) SM. (Nymphaeaceae) are used in traditional medicine for the treatment of arthritis, fever, aches, pains and inflammation. The main purpose of this study was to determine the anti-inflammatory effect of Nuphar lutea leaf extract (NUP) in two septic shock models: (1) Survival of mice challenged with a lethal dose of LPS, determination of pro-inflammatory and anti-inflammatory cytokines in serum, as well as in peritoneal macrophages in cell culture. (2) The effect of NUP in a murine model of fecal-induced peritonitis. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. A significant average survival rate (60%) of LPS lethally-challenged mice was achieved by pre-treatment with NUP. In addition, NUP pre-treatment reduced nuclear NF-κB translocation in peritoneal macrophages. The production of pro-inflammatory cytokines, TNF-α, IL-6 and IL-12, in the sera of LPS-treated mice or in the supernatants of peritoneal macrophages stimulated with LPS for 2-6 h was also decreased by NUP. Pre-treatment with NUP caused a significant increase in the anti-inflammatory cytokine IL-10. The NUP pre-treatment reduced and delayed mortality in mice with fecal-induced peritonitis. Our studies also revealed that NUP pre-treatment induced a dose-dependent phosphorylation of ERK in peritoneal macrophages. Since most of the reports about the anti-inflammatory effect of Nuphar lutea refer to rhizome and root powder and extracts, it is important to clarify the effectiveness of leaf extract as a source for such activity. NUP pre-treatment partially protected mice in two models of acute septic shock. We concluded that NUP is anti-inflammatory by inhibiting the NF-κB pathway, modulating cytokine production and ERK phosphorylation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells

PubMed Central

2014-01-01

Background Excessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, thus, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Among 5 selected brown algae, we found the highest antioxidant and anti-neuroinflammatory activities from Myagropsis myagroides ethanolic extract (MME) in lipopolysaccharide (LPS)-stimulated BV-2 cells. Methods The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunesorbent assay. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunefluorescence and reporter gene assay, respectively. Results MME inhibited the expression of iNOS and COX-2 at mRNA and protein levels, resulting in reduction of NO and PGE2 production. As a result, pro-inflammatory cytokines were reduced by MME. MME also inhibited the activation and translocation of NF-κB by preventing inhibitor κB-α (IκB-α) degradation. Moreover, MME inhibited the phosphorylation of extracellular signal regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs). Main anti-inflammatory compound in MME was identified as sargachromenol by NMR spectroscopy. Conclusions These results indicate that the anti-inflammatory effect of sargachromenol-rich MME on LPS-stimulated microglia is mainly regulated by the inhibition of IκB-α/NF-κB and ERK/JNK pathways. PMID:25005778

PDK1 in NF-κB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities.

PubMed

Hossen, Muhammad Jahangir; Cho, Jae Youl; Kim, Daewon

2016-08-22

Xanthium strumarium L. (Asteraceae) has traditionally been used to treat bacterial infections, nasal sinusitis, urticaria, arthritis, chronic bronchitis and rhinitis, allergic rhinitis, edema, lumbago, and other ailments. However, the molecular mechanisms by which this plant exerts its anti-inflammatory effects are poorly characterized. Here we studied the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Xs-ME) and validated its pharmacological targets. To evaluate the anti-inflammatory activity of Xs-ME, we employed lipopolysaccharide (LPS)-treated macrophages and an HCl/EtOH-induced mouse model of gastritis. We also used HPLC to identify the potentially active anti-inflammatory components of this extract. The molecular mechanisms of its anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) were both suppressed by Xs-ME. Moreover, orally administered Xs-ME ameliorated HCl/EtOH-induced gastric lesions. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signaling events upstream of NF-κB translocation, such as phosphorylation of AKT and the formation of PDK1-AKT signaling complexes, were also inhibited by Xs-ME. Moreover, Xs-ME suppressed the enzymatic activity of PDK1. Additionally, PDK1-induced luciferase activity and Akt phosphorylation were both inhibited by Xs-ME. We also identified the polyphenol resveratrol as a likely active anti-inflammatory component in Xs-ME that targets PDK1. Xs-ME exerts anti-inflammatory activity in vitro and in vivo by inhibiting PDK1 kinase activity and blocking signaling to its downstream transcription factor, NF-κB. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages.

PubMed

Chen, Chin-Chaun; Lin, Ming-Wei; Liang, Chan-Jung; Wang, Shu-Huei

2016-01-01

Eupafolin is a flavone isolated from Artemisia princeps Pampanini (family Asteraceae). The aim of this study was to examine the anti-inflammatory effects of eupafolin in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-induced mouse skin and lung inflammation models and to identify the mechanism underlying these effects. Eupafolin decreased the LPS-induced release of inflammatory mediators (iNOS, COX-2 and NO) and proinflammatory cytokines (IL-6 and TNF-α) from the RAW264.7 macrophages. Eupafolin inhibited the LPS-induced phosphorylation of p38 MAPK, ERK1/2, JNK, AKT and p65 and the nuclear translocation of p65 and c-fos. These effects were mainly mediated by the inhibition of JNK. In the mouse paw and lung models, eupafolin effectively suppressed the LPS-induced edema formation and down-regulated iNOS and COX-2 expression. These results demonstrated that eupafolin exhibits anti-inflammatory properties and suggested that eupafolin can be developed as an anti-inflammatory agent.

The Anti-Inflammatory Effects and Mechanisms of Eupafolin in Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages

PubMed Central

Chen, Chin-Chaun; Lin, Ming-Wei; Liang, Chan-Jung; Wang, Shu-Huei

2016-01-01

Eupafolin is a flavone isolated from Artemisia princeps Pampanini (family Asteraceae). The aim of this study was to examine the anti-inflammatory effects of eupafolin in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-induced mouse skin and lung inflammation models and to identify the mechanism underlying these effects. Eupafolin decreased the LPS-induced release of inflammatory mediators (iNOS, COX-2 and NO) and proinflammatory cytokines (IL-6 and TNF-α) from the RAW264.7 macrophages. Eupafolin inhibited the LPS-induced phosphorylation of p38 MAPK, ERK1/2, JNK, AKT and p65 and the nuclear translocation of p65 and c-fos. These effects were mainly mediated by the inhibition of JNK. In the mouse paw and lung models, eupafolin effectively suppressed the LPS-induced edema formation and down-regulated iNOS and COX-2 expression. These results demonstrated that eupafolin exhibits anti-inflammatory properties and suggested that eupafolin can be developed as an anti-inflammatory agent. PMID:27414646

Liquiritigenin attenuates cardiac injury induced by high fructose-feeding through fibrosis and inflammation suppression.

PubMed

Xie, Xiong-Wei

2017-02-01

Diabetes combined with cardiomyopathy is considered as an essential complication, showing diastolic persistently and causing cardiac injury, which is linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for cardiomyopathy. Liquiritigenin is a flavanone, isolated from Radix glycyrrhiza, which exhibits various biological properties, including anti-cancer and anti-inflammatory activities. Here, in our study, the protective effects and anti-inflammatory activity of liquiritigenin were explored in mice and cardiac muscle cells treated by fructose to reveal the possible mechanism by which liquiritigenin attenuates cardiac injury. The mice were separated into five groups. The diabetic model of mouse was established with 30% high fructose feeding. Liquiritigenin dramatically reduced the lipid accumulation induced by high fructose diet. Compared to mice only treated with high fructose, mice in the presence of liquiritigenin after fructose feeding developed less cardiac fibrosis with lower levels of alpha smooth muscle-actin (α-SMA), Collagen type I, Collagen type II, TGF-β1 and Procol1a1. Additionally, liquiritigenin markedly down-regulated inflammatory cytokines secretion and phosphorylated NF-κB via inhibiting IKKα/IκBα signaling pathway. Our results indicate that liquiritigenin has a protective role in high fructose feeding-triggered cardiac injury through fibrosis and inflammation response suppression by inactivating NF-κB signaling pathway. Thus, liquiritigenin may be a potential candidate for diabetes-associated cardiac injury. Copyright © 2016. Published by Elsevier Masson SAS.

Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB pathway.

PubMed

Jiang, Kang-Feng; Zhao, Gan; Deng, Gan-Zhen; Wu, Hai-Chong; Yin, Nan-Nan; Chen, Xiu-Ying; Qiu, Chang-Wei; Peng, Xiu-Li

2017-02-01

Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation. Furthermore, PD treatment dose-dependently decreased the levels of TNF-α, IL-1β, IL-6 and IL-8 in the mammary gland tissues. PD treatment also dose-dependently decreased the expression of TLR2, MyD88, IRAK1, IRAK4 and TRAF6 as well as the phosphorylation of TAK1, MKK3/6, p38 MAPK, IκB-α and NF-κB in the mammary gland tissues. In mouse mammary epithelial cells (mMECs) infected by S aureus in vitro, pretreatment with PD dose-dependently suppressed the upregulated pro-inflammatory cytokines and signaling proteins, and the nuclear translocation of NF-κB p65 and AP-1. A TLR2-neutralizing antibody mimicked PD in its suppression on S aureus-induced upregulation of MyD88, p-p38 and p-p65 levels in mMECs. PD (50, 100 μg/mL) affected neither the growth of S aureus in vitro, nor the viability of mMECs. In conclusion, PD does not exhibit antibacterial activity against S aureus, its therapeutic effects in mouse S aureus-induced mastitis depend on its ability to down-regulate pro-inflammatory cytokine levels via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB signaling pathway.

Pinocembrin attenuates lipopolysaccharide-induced inflammatory responses in Labeo rohita macrophages via the suppression of the NF-κB signalling pathway.

PubMed

Giri, Sib Sankar; Sen, Shib Sankar; Sukumaran, Venkatachalam; Park, Se Chang

2016-09-01

Pinocembrin is a flavonoid that has been reported to exhibit various pharmacological and biological activities including antimicrobial, antioxidant, and anti-inflammatory. To explore the anti-inflammatory activity of pinocembrin in a fish cell line, we investigated its ability to regulate the inflammatory mediators elevated by lipopolysaccharide (LPS) in Labeo rohita head-kidney (HK) macrophages. HK macrophages of L. rohita were treated with LPS (1 μg mL(-1)) in the presence or absence of pinocembrin. We examined the inhibitory effect of pinocembrin on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. The inhibitory effect of pinocembrin on nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was investigated by RT-PCR and western blot. The effect of pinocembrin on pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β)) and anti-inflammatory cytokine IL-10 was investigated by ELISA and RT-PCR. The phosphorylation of three mitogen activated protein kinases (MAPKs) ERK, JNK, and p38 was analysed by western blot. Pinocembrin inhibited LPS-induced productions of NO and PGE2, and also markedly inhibited TNF-α, IL-1β, iNOS, and COX-2 production in a concentration-dependent manner. In addition, TNF-α and IL-1β mRNA expression levels decreased significantly, while IL-10 mRNA expression increased (P < 0.05) with pinocembrin pre-treatment. RT-PCR and western blot analysis showed that pinocembrin decreased both the mRNA and protein expression levels of LPS-induced iNOS and COX-2 in HK macrophages. Pinocembrin suppressed the phosphorylation of MAPK in LPS-stimulated HK macrophages. Further, pinocembrin significantly inhibited LPS-induced NF-κB transcriptional activity via the attenuation of IκBα degradation. Taken together, pinocembrin reduced the levels of pro-inflammatory mediators, such as iNOS, COX-2, TNF-α, and IL-1β, by inhibiting NF-κB activation via the suppression of ERK and p38 phosphorylation, and by attenuating the degradation of IκBα. These results suggest that pinocembrin is a potential novel candidate for the treatment of inflammatory conditions in L. rohita macrophages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploration of avocado by-products as natural sources of bioactive compounds.

PubMed

Tremocoldi, Maria Augusta; Rosalen, Pedro Luiz; Franchin, Marcelo; Massarioli, Adna Prado; Denny, Carina; Daiuto, Érica Regina; Paschoal, Jonas Augusto Rizzato; Melo, Priscilla Siqueira; Alencar, Severino Matias de

2018-01-01

This study aimed to evaluate the antioxidant, anti-inflammatory, and cytotoxic properties and phenolic composition of peel and seed of avocado varieties Hass and Fuerte using green solvents. Ethanol soluble compounds were identified in peel and seed of both varieties using HPLC-MS/MS and quantified using HPLC-DAD. Agro-industrial by-products of both varieties exhibited high radical scavenging activity against synthetic free radicals (DPPH and ABTS) and reactive oxygen species (peroxyl, superoxide, and hypochlorous acid) and high ability to reduce Fe3+ to Fe2+. The main compounds with significant contribution to the antioxidant activity determined by online HPLC-ABTS●+ analyses were procyanidin B2 and epicatechin in the peel and trans-5-O-caffeoyl-D-quinic acid, procyanidin B1, catechin, and epicatechin in the seed. Peel of Fuerte significantly suppressed TNF-α and nitric oxide (NO) release (459.3 pg/mL and 8.5 μM, respectively), possibly because of the high phenolic content and antioxidant activity detected. Avocado agro-industrial by-products can be used for food and pharmaceutical purposes due to their antioxidant and anti-inflammatory properties.

Exploration of avocado by-products as natural sources of bioactive compounds

PubMed Central

Tremocoldi, Maria Augusta; Rosalen, Pedro Luiz; Franchin, Marcelo; Massarioli, Adna Prado; Denny, Carina; Daiuto, Érica Regina; Paschoal, Jonas Augusto Rizzato; Melo, Priscilla Siqueira

2018-01-01

This study aimed to evaluate the antioxidant, anti-inflammatory, and cytotoxic properties and phenolic composition of peel and seed of avocado varieties Hass and Fuerte using green solvents. Ethanol soluble compounds were identified in peel and seed of both varieties using HPLC-MS/MS and quantified using HPLC-DAD. Agro-industrial by-products of both varieties exhibited high radical scavenging activity against synthetic free radicals (DPPH and ABTS) and reactive oxygen species (peroxyl, superoxide, and hypochlorous acid) and high ability to reduce Fe3+ to Fe2+. The main compounds with significant contribution to the antioxidant activity determined by online HPLC-ABTS●+ analyses were procyanidin B2 and epicatechin in the peel and trans-5-O-caffeoyl-D-quinic acid, procyanidin B1, catechin, and epicatechin in the seed. Peel of Fuerte significantly suppressed TNF-α and nitric oxide (NO) release (459.3 pg/mL and 8.5 μM, respectively), possibly because of the high phenolic content and antioxidant activity detected. Avocado agro-industrial by-products can be used for food and pharmaceutical purposes due to their antioxidant and anti-inflammatory properties. PMID:29444125

Anti-inflammatory Ingenane Diterpenoids from the Roots of Euphorbia kansui.

PubMed

Zhang, Jun-Sheng; Weng, Han-Zhuang; Huang, Jia-Luo; Tang, Gui-Hua; Yin, Sheng

2018-06-25

Bioassay-guided fractionation of the ethanolic extract of the roots of Euphorbia kansui led to the isolation of two new ingenane diterpenoids, euphorkans A (1: ) and B (2: ), together with 16 known analogues (3:  - 18: ). Their structures were determined by combined spectral and chemical methods. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. Compounds 1:  - 6: and 10:  - 13: exhibited pronounced inhibitory activity with IC 50 values in the range of 2.78 - 10.6 µM, and were more potent than the positive control, quercetin (IC 50  = 15.8 µM). Compounds 1: and 5: were selected for further assays toward the key inflammation mediators TNF- α and IL-6, and showed a significant inhibition in a dose-dependent manner. The preliminary mechanistic study revealed that 1: and 5: inhibited NF- κ B activity, which may exert a role in their anti-inflammatory activity. Georg Thieme Verlag KG Stuttgart · New York.

Anti-Inflammatory Properties of Brazilian Green Propolis Encapsulated in a γ-Cyclodextrin Complex in Mice Fed a Western-Type Diet.

PubMed

Rimbach, Gerald; Fischer, Alexandra; Schloesser, Anke; Jerz, Gerold; Ikuta, Naoko; Ishida, Yoshiyuki; Matsuzawa, Ryota; Matsugo, Seiichi; Huebbe, Patricia; Terao, Keiji

2017-05-26

Ageing is often accompanied by chronic inflammation. A fat- and sugar-rich Western-type diet (WTD) may accelerate the ageing phenotype. Cell culture studies have indicated that artepillin C-containing Brazilian green propolis exhibits anti-inflammatory properties. However, little is known regarding its anti-inflammatory potential in mouse liver in vivo. In this study, female C57BL/6NRj wild-type mice were fed a WTD, a WTD supplemented with Brazilian green propolis supercritical extract (GPSE) encapsulated in γ-cyclodextrin (γCD) or a WTD plus γCD for 10 weeks. GPSE-γCD did not affect the food intake, body weight or body composition of the mice. However, mRNA levels of the tumour necrosis factor α were significantly downregulated ( p < 0.05) in these mice compared to those in the WTD-fed controls. Furthermore, the gene expression levels of other pro-inflammatory markers, including serum amyloid P, were significantly ( p < 0.001) decreased following GPSE-γCD treatment. GPSE-γCD significantly induced hepatic ferritin gene expression ( p < 0.01), which may contribute to its anti-inflammatory properties. Conversely, GPSE-γCD did not affect the biomarkers of endogenous antioxidant defence, including catalase, glutathione peroxidase-4, paraoxonase-1, glutamate cysteine ligase and nuclear factor erythroid 2-related factor-2 (Nrf2). Overall, the present data suggest that dietary GPSE-γCD exhibits anti-inflammatory, but not antioxidant activity in mouse liver in vivo. Thus, GPSE-γCD has the potential to serve as a natural hepatoprotective bioactive compound for dietary-mediated strategies against chronic inflammation.

Identification and evaluation of anti-inflammatory properties of aqueous components extracted from sesame (Sesamum indicum) oil.

PubMed

Deme, Pragney; Narasimhulu, Chandrakala Aluganti; Parthasarathy, Sampath

2018-06-15

We previously reported that sesame oil (SO) has anti-inflammatory, anti-atherosclerotic and lipid lowering properties in vivo. Our recent studies have shown that, an aqueous extract of sesame oil (SOAE) has also anti-inflammatory and anti-atherosclerotic properties but with no lipid lowering effects. The extent of reduction in atherosclerosis led us to identify components of SOAE and evaluate their anti-inflammatory properties in vitro. Liquid chromatography mass spectrometric method was used to detect and identify components of SOAE. Methoxyphenol derivatives, short and long chain carboxylic acids, dicarboxylic acids, hydroxy and oxo- carboxylic acids were detected. To our surprise, sesamol and its derivatives (lignans), were not present in the SOAE. Among the identified, a combination of methoxy phenol compounds were selected and tested their ability to reduce LPS induced inflammatory gene expression. Monocyte derived macrophages/RAW 264.7 macrophages were pre-treated with these compounds for 2 h, followed by LPS stimulation for 24 h and pro-inflammatory gene expressions were analyzed. These methoxyphenol derivatives showed potent anti-inflammatory properties. In conclusion, the anti-inflammatory molecules associated with SO may contribute the anti-inflammatory and anti-atherosclerotic properties. Also, our results shed light for the development of SOAE based non-pharmacological therapeutics, nutritional supplements and health products for various inflammatory diseases in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats.

PubMed

Subramanian, Perumal; Jayakumar, Murugesan; Jayapalan, Jaime Jacqueline; Hashim, Onn Haji

2014-12-01

Elevated blood ammonia leads to hyperammonaemia that affects vital central nervous system (CNS) functions. Fisetin, a naturally occurring flavonoid, exhibits therapeutic benefits, such as anti-cancer, anti-diabetic, anti-oxidant, anti-angiogenic, neuroprotective and neurotrophic effects. In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis. Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points. Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Modulatory effect of standardised amentoflavone isolated from Juniperus communis L. agianst Freund's adjuvant induced arthritis in rats (histopathological and X Ray anaysis).

PubMed

Bais, Souravh; Abrol, Naveena; Prashar, Yash; Kumari, Renu

2017-02-01

Juniperus communis. L. is a shrub or small evergreen tree, native to Europe, South Asia, and North America, and belongs to family Cupressaceae. It has been used traditionally in unani system and in Swedish medicine as a decoction in inflammatory diseases. The main chemical constituents, which were reported in J. communis L. was α-pinene,, apigenin, sabinene, β-sitosterol, campesterol, limonene, Amentoflavone (AF), cupressuflavone, and many others. The aim of present study was to isolate the amentoflavone from the plant juniperus communis L. extracts and its protective effects against Freund's adjuvant induced arthritis in rats. Adjuvant arthritis was induced by an injection of 1mg heat killed Mycobacterium tuberculosis (CFA) into the left hind paw of rat by sub planter route (at day 0). The experiment was designed and modified as per method available in literature. The study showed that at a dose of 40mg/kg of amentoflavone (AF) from methanolic extract of Juniperus Communis L. possessed potentially useful anti-arthritic activity as it gave a positive result in controlling inflammation in the adjuvant induced experimental model. From the present experimental findings of both pharmacological and biochemical parameters observed, it had been concluded that at the doses of 20mg/kg and 40mg/kg of AF fraction from methanolic extract of Juniperus communis L. It possesses useful anti-arthritic activity since it gives a positive result in controlling inflammation in the adjuvant induced arthritic model in rats. The drug is a promising anti-arthritic agent of plant origin in the treatment of inflammatory disorders. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen)

NASA Astrophysics Data System (ADS)

Gao, Hongwei; Sun, Wen; Zhao, Jianping; Wu, Xiaxia; Lu, Jin-Jian; Chen, Xiuping; Xu, Qiong-Ming; Khan, Ikhlas A.; Yang, Shilin

2016-09-01

Four novel compounds (1-4) as well as fourteen reported compounds (5-18) were isolated and purified from Salvia miltiorrhiza Bunge (Danshen). The structures of novel compounds were determined by 1D and 2D NMR, HRESIMS data, etc. The anti-inflammatory properties of all the compounds on RAW264.7 macrophages and their cytotoxicity on H1299 and Bel-7402 cell lines coupled with a structure-activity relationship (SAR) were investigated. Compound 4 demonstrated the best anti-inflammatory activity and was chosen for further research. Compound 4 greatly suppressed secretion of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) in the RAW264.7 macrophages stimulated by LPS. Additionally, the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased and the nuclear translocation of NF-κB was attenuated after treatment with compound 4 in vitro. Compound 4 was able to dramatically inhibit LPS-induced activation of JNK1/2 and ERK1/2 and remarkably disrupted the TLR4 dimerization in LPS-induced RAW264.7 macrophages. Thus, the new compound 4 suppressed LPS-induced inflammation partially is due to the blocking TLR4 dimerization. In addition, the anti-cancer activity investigation indicated that most of isolated compounds exhibited cytotoxicity and the SAR analysis showed that the intact D ring was indispensable and unsaturated D ring played vital role.

Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway.

PubMed

Huang, Wei; Li, Ming-Li; Xia, Ming-Yue; Shao, Jian-Ying

2018-07-01

Asthma is a common chronic airway inflammation disease and is considered as a major public health problem. Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid abundantly found in different vegetables and fruits. Fisetin has been reported to exhibit various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. We evaluated the effects of fisetin on allergic asthma regulation in mice. Mice were first sensitized, then airway-challenged with ovalbumin (OVA). Whether fisetin treatment attenuated OVA-induced airway inflammation was examined via inflammation inhibition through MyD88-related NF-κB (p65) signaling pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40 (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results found that OVA-induced airway inflammation in mice caused a significant inflammatory response via the activation of MyD88 and NF-κB signaling pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin-treated mice after OVA induction inhibited activation of MyD88 and NF-κB signaling pathways, resulting in downregulation of pro-inflammatory cytokine secretion. Further, fisetin significantly ameliorated the airway hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin reduced the number of eosinophil, monocyte, neutrophil and total white blood cell in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and BALF samples obtained from the OVA-induced mice with fisetin showed lower levels of pro-inflammatory cytokines. The results of our study illustrated that fisetin may be a new promising candidate to inhibit airway inflammation response induced by OVA.

Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway

PubMed Central

Huang, Wei; Li, Ming-Li; Xia, Ming-Yue; Shao, Jian-Ying

2018-01-01

Asthma is a common chronic airway inflammation disease and is considered as a major public health problem. Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a naturally occurring flavonoid abundantly found in different vegetables and fruits. Fisetin has been reported to exhibit various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. We evaluated the effects of fisetin on allergic asthma regulation in mice. Mice were first sensi-tized, then airway-challenged with ovalbumin (OVA). Whether fisetin treatment attenuated OVA-induced airway inflammation was examined via inflammation inhibition through MyD88-related NF-κB (p65) signaling pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40 (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results found that OVA-induced airway inflammation in mice caused a significant inflammatory response via the activation of MyD88 and NF-κB signaling pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin-treated mice after OVA induction inhibited activation of MyD88 and NF-κB signaling pathways, resulting in downregulation of pro-inflammatory cytokine secretion. Further, fisetin significantly ameliorated the airway hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin reduced the number of eosinophil, monocyte, neutrophil and total white blood cell in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and BALF samples obtained from the OVA-induced mice with fisetin showed lower levels of pro-inflammatory cytokines. The results of our study illustrated that fisetin may be a new promising candidate to inhibit airway inflammation response induced by OVA. PMID:29568921

Secondary metabolites from Sida rhombifolia L. (Malvaceae) and the vasorelaxant activity of cryptolepinone.

PubMed

Chaves, Otemberg Souza; Gomes, Roosevelt Albuquerque; Tomaz, Anna Cláudia de Andrade; Fernandes, Marianne Guedes; das Graças Mendes, Leônidas; de Fátima Agra, Maria; Braga, Valdir Andrade; de Fátima Vanderlei de Souza, Maria

2013-03-01

The phytochemical study of Sida rhombifolia L. (Malvaceae) led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a) and stigmasterol (1b), sitosterol-3-O-b-D-glucopyranoside (2a) and stigmasterol-3-O-b-D-glucopyranoside (2b), phaeophytin A (3), 17³-ethoxypheophorbide A (4), 13²-hydroxy phaeophytin B (5), 17³-ethoxypheophorbide B (6), 5,7-dihydroxy-4'-methoxyflavone (7), cryptolepinone (8) and a salt of cryptolepine (9). Their structures were identified by ¹H- and ¹³C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time.

Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice.

PubMed

Colombo, Bárbara B; Fattori, Victor; Guazelli, Carla F S; Zaninelli, Tiago H; Carvalho, Thacyana T; Ferraz, Camila R; Bussmann, Allan J C; Ruiz-Miyazawa, Kenji W; Baracat, Marcela M; Casagrande, Rúbia; Verri, Waldiceu A

2018-04-10

The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

Extra virgin olive oil polyphenolic extracts downregulate inflammatory responses in LPS-activated murine peritoneal macrophages suppressing NFκB and MAPK signalling pathways.

PubMed

Cárdeno, A; Sánchez-Hidalgo, M; Aparicio-Soto, M; Sánchez-Fidalgo, S; Alarcón-de-la-Lastra, C

2014-06-01

Extra virgin olive oil (EVOO) is obtained from the fruit of the olive tree Olea europaea L. Phenolic compounds present in EVOO have recognized anti-oxidant and anti-inflammatory properties. However, the activity of the total phenolic fraction extracted from EVOO and the action mechanisms involved are not well defined. The present study was designed to evaluate the potential anti-inflammatory mechanisms of the polyphenolic extract (PE) from EVOO on LPS-stimulated peritoneal murine macrophages. Nitric oxide (NO) production was analyzed by the Griess method and intracellular reactive oxygen species (ROS) by fluorescence analysis. Moreover, changes in the protein expression of the pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1), as well as the role of nuclear transcription factor kappa B (NFκB) and mitogen-activated protein kinase (MAPK) signalling pathways, were analyzed by Western blot. PE from EVOO reduced LPS-induced oxidative stress and inflammatory responses through decreasing NO and ROS generation. In addition, PE induced a significant down-regulation of iNOS, COX-2 and mPGES-1 protein expressions, reduced MAPK phosphorylation and prevented the nuclear NFκB translocation. This study establishes that PE from EVOO possesses anti-inflammatory activities on LPS-stimulated murine macrophages.

Anti-inflammatory activity of methylene chloride fraction from Glehnia littoralis extract via suppression of NF-kappa B and mitogen-activated protein kinase activity.

PubMed

Yoon, Taesook; Cheon, Myeong Sook; Lee, A Yeong; Lee, Do Yeon; Moon, Byeong Cheol; Chun, Jin Mi; Choo, Byung Kil; Kim, Ho Kyoung

2010-01-01

Glehnia littoralis (Umbelliferae) has been used traditionally in Korean, Japanese, and Chinese medicine for the treatment of immune-related diseases; however, its anti-inflammatory activity and underlying mechanism remain to be defined. We investigated the anti-inflammatory effect and inhibitory mechanism on inflammation by the methylene chloride fraction from Glehnia littoralis extract (MCF-GLE), which was more effective than Glehnia littoralis extract (GLE). MCF-GLE inhibited 12-O-Tetradecanoyl-phorbol-13-acetate (TPA)-induced inflammation in an inflammatory edema mouse model. Also, MCF-GLE strongly inhibited the releases of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) and significantly suppressed the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW 264.7 macrophage cells in a dose-dependent manner. Furthermore, MCF-GLE suppressed NF-kappaB activation and IkappaB-alpha degradation. MCF-GLE also attenuated the activation of ERK and JNK in a dose-dependent manner. These results indicate that MCF-GLE has an inhibitory effect on the in vivo and in vitro inflammatory reaction and is a possible therapeutic agent. Our results suggest that the anti-inflammatory properties of MCF-GLE may result from the inhibition of pro-inflammatory mediators, such as NO, PGE(2), TNF-alpha, and IL-1beta via suppression of NF-kappaB- and mitogen-activated protein kinases-dependent pathways.

Modulation of NF-κB activation by resveratrol in LPS treated human intestinal cells results in downregulation of PGE2 production and COX-2 expression.

PubMed

Cianciulli, Antonia; Calvello, Rosa; Cavallo, Pasqua; Dragone, Teresa; Carofiglio, Vito; Panaro, Maria Antonietta

2012-10-01

Resveratrol is a natural phytoalexin present in a variety of plant species, such as grapes and red wine, that is well known for its anti-inflammatory effects. In addition, a cancer chemotherapeutic activity of resveratrol has been described. Here we evaluated the effect of resveratrol on COX-2 and prostaglandin E(2) production in human intestinal cells Caco-2 cells treated with lipopolysaccharide (LPS). Resveratrol concentration-dependently inhibited the expression of COX-2 mRNA in the LPS-treated cells, as well as protein expression, resulting in a decreased production of PGE(2). In order to investigate the mechanisms through which resveratrol exhibited these anti-inflammatory effects, we examined the activation of IκB in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the translocation of NF-κB p65 subunits from the cytosol to the nucleus, which correlated with its inhibitory effects on IκBα phosphorylation and degradation. These results suggest that the down-regulation of COX-2 and PGE(2) by resveratrol may be related to NF-κB inhibition through the negative regulation of IKK phosphorylation in intestinal cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased monocyte adhesion-promoting capacity of plasma in end-stage renal disease - response to antioxidant therapy.

PubMed

Moradi, H; Ganji, S; Kamanna, V; Pahl, M V; Vaziri, N D

2010-10-01

End-stage renal disease (ESRD) causes accelerated atherosclerosis which is mediated by oxidative stress and inflammation. Activation and infiltration of monocytes represent the critical steps in atherogenesis which is advanced by oxidized LDL and inhibited by HDL. Via its main apolipoprotein (apoA-I) and constituent enzymes (paraoxonase; glutathione peroxidase (GPX), LCAT) HDL exerts potent antioxidant/anti-inflammatory functions. We have found marked reduction of HDL antioxidant/anti-inflammatory and heightened LDL pro-oxidant/pro-inflammatory activities in ESRD patients. Given the inseparable link between oxidative stress and inflammation, we tested the hypothesis that antioxidant therapy may improve anti-inflammatory (monocyte adhesion-promoting capacity) properties of plasma in ESRD patients. We studied 20 hemodialysis patients who after a 4-week wash-out period were treated with a potent antioxidant cocktail (vitamin (v) E, 800 IU; vC, 250 mg; vB6, 100 mg; vB12, 250 µg and folic acid 10 mg daily) for 8 weeks. Twelve healthy volunteers served as control. Pre-dialysis plasma samples were obtained at the onset and conclusion of the study. Markers of oxidative stress and inflammation, apoA-I, HDL-associated enzymes and monocyte adhesion assay were measured using cultured aortic endothelial cells. ESRD patients exhibited reduced plasma level of apoA-1 and antioxidant enzymes, elevated markers of oxidative stress and inflammation and heightened monocyte adhesion-promoting capacity. Antioxidant therapy failed to improve these abnormalities. High doses of antioxidant vitamins fail to improve oxidative stress, inflammation or plasma monocyte adhesion-promoting capacity in ESRD patients. Thus, high doses of vitamins beyond the routinely-prescribed supplements do not appear to be beneficial in this patient population.

Anti-inflammatory effects of physalin E from Physalis angulata on lipopolysaccharide-stimulated RAW 264.7 cells through inhibition of NF-κB pathway.

PubMed

Yang, Yan-Jun; Yi, Lang; Wang, Qing; Xie, Bing-Bing; Dong, Yan; Sha, Cong-Wei

2017-04-01

Physalin E is a naturally occurring seco-steroid isolated from the stems and aerial parts of Physalis angulata L. (Solanaceae). This study was aimed to explore the anti-inflammatory effects of physalin E on RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS) and the potential underlying mechanisms. The results showed that physalin E significantly inhibited LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression and secretion in a dose-dependent manner. Unlike dexamethasone, these effects could not be blocked by miferstone (RU486). Meanwhile, physalin E reduced the degradation of I-kappa B protein in the cytoplasm and downregulated the nuclear factor-κB (NF-κB) p65 protein in the nuclear, which resulted in the inhibition of the NF-κB nuclear translocation. In conclusion, physalin E exerts its anti-inflammatory activities in LPS-induced macrophages. Physalin E can inhibit the production of inflammatory cytokines by targeting the NF-κB signaling pathway.

Isoflavones: Anti-Inflammatory Benefit and Possible Caveats

PubMed Central

Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

2016-01-01

Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks. PMID:27294954

Isoflavones: Anti-Inflammatory Benefit and Possible Caveats.

PubMed

Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

2016-06-10

Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks.

JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38

PubMed Central

Yi, Young-Su

2017-01-01

Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1b without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the NF-kB transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the NF-kB pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPS-stimulated RAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the NF-kB and AP-1 pathways, respectively. PMID:28461777

JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38.

PubMed

Yi, Young-Su; Kim, Mi-Yeon; Cho, Jae Youl

2017-05-01

Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1b without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the NF-kB transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the NF-kB pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPS-stimulated RAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the NF-kB and AP-1 pathways, respectively.

The effect of ultraviolet radiation on the anti-inflammatory effect of filters.

PubMed

Couteau, C; Couteau, O; Chauvet, C; Paparis, E; Coiffard, L J M

2013-08-16

A certain number of filters have notable anti-inflammatory properties with percentage inhibition of PMA-induced edema in mice at over 70%. The question arose as to whether this effect was likely to continue after UV irradiation. It can be noted that 7 filters retain an equivalent anti-inflammatory effect before and after 2h of irradiation in a Suntest device (650 W/m(2)). For 9 filters, the anti-inflammatory effect decreases and for 5 filters, the anti-inflammatory effect increases. Various behaviors should be noted. 3 groups of substances can be distinguished: such as phenylbenzimidazole sulfonic acid which loses its anti-inflammatory character after irradiation (the percentage inhibition falls from 80 to 44%), oxybenzone which retains a constant anti-inflammatory character (89% inhibition before and after irradiation and also octyl methoxycinnamate which becomes very anti-inflammatory (with a percentage inhibition of 93%). The same phenomenon is observed in the case of commercial products. This should be made known as it can have a considerable impact on the results which are displayed on the packaging of sun products. Copyright © 2013 Elsevier B.V. All rights reserved.

Sinensetin attenuates LPS-induced inflammation by regulating the protein level of IκB-α.

PubMed

Shin, Hye-Sun; Kang, Seong-Il; Yoon, Seon-A; Ko, Hee-Chul; Kim, Se-Jae

2012-01-01

Sinensetin is one of the polymethoxyflavones (PMFs) having five methoxy groups on the basic benzo-γ-pyrone skeleton with a carbonyl group at the C(4) position. We investigated in this study the anti-inflammatory activity of sinensetin in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Sinensetin showed anti-inflammatory activity by regulating the protein level of inhibitor κB-α (IκB-α).

Cinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-κB.

PubMed

Franchin, Marcelo; Rosalen, Pedro Luiz; da Cunha, Marcos Guilherme; Silva, Rangel Leal; Colón, David F; Bassi, Gabriel Shimizu; de Alencar, Severino Matias; Ikegaki, Masaharu; Alves-Filho, José C; Cunha, Fernando Q; Beutler, John A; Cunha, Thiago Mattar

2016-07-22

Chemical compounds belonging to the class of coumarins have promising anti-inflammatory potential. Cinnamoyloxy-mammeisin (CNM) is a 4-phenylcoumarin that can be isolated from Brazilian geopropolis. To our knowledge, its anti-inflammatory activity has never been studied. Therefore, the present study investigated the anti-inflammatory activity of CNM and elucidated its mechanism of action on isolated macrophages. Pretreatment with CNM reduced neutrophil migration into the peritoneal and joint cavity of mice. Likewise, CNM reduced the in vitro and in vivo release of TNF-α and CXCL2/MIP-2. Regarding the possible molecular mechanism of action, CNM reduced the phosphorylation of proteins ERK 1/2, JNK, p38 MAPK, and AP-1 (subunit c-jun) in PG-stimulated macrophages. Pretreatment with CNM also reduced NF-κB activation in RAW 264.7 macrophages stably expressing the NF-κB-luciferase reporter gene. On the other hand, it did not alter IκBα degradation or nuclear translocation of p65. Thus, the results of this study demonstrate promising anti-inflammatory activity of CNM and provide an explanation of its mechanism of action in macrophages via inhibition of MAPK signaling, AP-1, and NF-κB.

Antibacterial and anti-inflammatory activities of extract and fractions from Pyrrosia petiolosa (Christ et Bar.) Ching.

PubMed

Cheng, Dandan; Zhang, Yingying; Gao, Demin; Zhang, Hongmeng

2014-09-11

Pyrrosia petiolosa is commonly used as a traditional Chinese medicine for treatment of acute pyelonephritis, chronic bronchitis and bronchial asthma. This study aims to evaluate the antibacterial activity of the ethanol extract and its derived fractions of Pyrrosia petiolosa obtained with solvents of different polarities and to perform the anti-inflammatory screening. The powdered aerial parts of Pyrrosia petiolosa were used to extract various fractions with ethanol, petroleum ether, ethyl acetate, N-butanol and aqueous. Qualitative phytochemical screening was performed on the ethanol extract, petroleum ether fraction, ethyl acetate fraction, N-butanol fraction and aqueous fraction. The agar diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were employed to evaluate antibacterial activity of the ethanol extract and fractions. The in vitro cytotoxicity of ethanol extract and fractions was determined using MTT assay. The anti-inflammatory activity was analyzed using the mouse ear swelling induced by xylene. The phytochemical screening revealed the presence of anthraquinones, flavonoids, terpenoids, steroids, saponins, phenols and reducing sugars in the extract and fractions. Antibacterial results showed that petroleum ether fraction and N-butanol fraction inhibited all the tested microorganisms with the maximum inhibition zone of 15.25±0.35 mm. Ethyl acetate fraction also exhibited good antibacterial activity except Pseudomonas aeruginosa ATCC 27853, while extract and aqueous fraction inhibited 8 out of 13 (61.5%) of the tested microorganisms. The MIC values of ethanol extract and fractions ranged from 1.25 to 10.00 mg/mL and most of the MBC values were equal or twice as high as the corresponding MIC values. The in vitro cytotoxicity showed the ethanol extract and fractions exhibited non-toxic or low toxic activity against lung cancer cell lines A549 and mouse spleen cells. In anti-inflammatory experiment, ethanol extract at 5.0 and 10.0 mg/kg exhibited significant anti-inflammatory activity against the mouse ear swelling induced by xylene and the maximum inhibition rate reached as high as 67%. Pyrrosia petiolosa could be a potential candidate for future development of a novel antibacterial and anti-inflammatory agent. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Alpha-Melanocyte Stimulating Hormone: An Emerging Anti-Inflammatory Antimicrobial Peptide

PubMed Central

Singh, Madhuri; Mukhopadhyay, Kasturi

2014-01-01

The alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide belonging to the melanocortin family. It is well known for its anti-inflammatory and antipyretic effects and shares several characteristics with antimicrobial peptides (AMPs). There have been some recent reports about the direct antimicrobial activity of α-MSH against various microbes belonging to both fungal and bacterial pathogens. Similar to α-MSH's anti-inflammatory properties, its C-terminal residues also exhibit antimicrobial activity parallel to that of the entire peptide. This review is focused on the current findings regarding the direct antimicrobial potential and immunomodulatory mechanism of α-MSH and its C-terminal fragments, with particular emphasis on the prospects of α-MSH based peptides as a strong anti-infective agent. PMID:25140322

Inhibitory effects of quercetin on the progression of liver fibrosis through the regulation of NF-кB/IкBα, p38 MAPK, and Bcl-2/Bax signaling.

PubMed

Wang, Rong; Zhang, Hai; Wang, Yuanyuan; Song, Fuxing; Yuan, Yongfang

2017-06-01

Quercetin, a natural flavonoid, has been used as a nutritional supplement for its anti-inflammatory and antioxidative properties. Quercetin was reported to exhibit a wide range of pharmacological properties, including its effect on anti-hepatic fibrosis. However, the anti-fibrotic mechanisms of quercetin have not been well-characterized to date. This study aimed to investigate the protective effects of quercetin on carbon tetrachloride (CCl 4 )-induced liver fibrosis in rats and to clarify its anti-hepatofibrotic mechanisms. We demonstrated that quercetin exhibited in-vivo hepatoprotective and anti-fibrogenic effects against CCl 4 -induced liver injury by improving the pathological manifestations, thereby reducing the activities of serum total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and decreasing the serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C) and procollagen III peptide (PIIIP). Furthermore, treatment with quercetin 5-15mg/kg inhibited the activation of NF-κB in a dose-dependent manner via inhibition of IкBα degradation and decreased the expression of p38 MAPK by inhibiting its phosphorylation. Additionally, in a dose-dependent manner, quercetin down-regulated Bax, up-regulated Bcl-2, and subsequently inhibited caspase-3 activation. Moreover, quercetin regulated inflammation factors and hepatic stellate cells (HSCs)-activation markers, such as TNF-α, IL-6, IL-1β, Cox-2, TGF-β, α-SMA, Colla1, Colla2, TIMP-1, MMP-1, and desmin. Taken together, quercetin prevented the progression of liver fibrosis in SD rats. The anti-fibrotic mechanisms of quercetin might be associated with its ability to regulate NF-кB/IкBα, p38 MAPK anti-inflammation signaling pathways to inhibit inflammation, and regulate Bcl-2/Bax anti-apoptosis signaling pathway to prevent liver cell apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of phenolic composition, antioxidant, anti-inflammatory and anticancer activities of Polygonatum verticillatum (L.).

PubMed

Kumar Singh, Sandeep; Patra, Arjun

2018-04-18

Polygonatum verticillatum (L.) All. (Ruscaceae), one of the Ashtawarga plants, is widely used for treatment of various ailments. The present study was undertaken to determine the phenolic composition, antioxidant, anti-inflammatory and anticancer activities of several extracts (petroleum ether, dichloromethane, chloroform, ethanol, and aqueous) from the rhizomes of the plant. Coarsely powdered dry rhizome was successively extracted with different solvents of increasing polarity (petroleum ether, dichloromethane, chloroform, ethanol and water). The phenolic compositions, in terms of total phenolic content (TPC), total flavonoid content (TFC) and total condensed tannin content (TTC), were evaluated with the Folin-Ciocalteu assay, aluminum chloride colorimetric assay and vanillin spectrophotometric assay, respectively. Total antioxidant capacity, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays were used to assess the antioxidant potential of each extract. A protein denaturation model and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used to evaluate in vitro anti-inflammatory and anticancer activities, respectively. Gas chromatography-mass spectrometry (GC/MS) analysis was carried out to demonstrate various phytoconstituents in each extract. Correlation studies were also performed between phenolic composition (TPC, TFC and TTC) and different biological activities. Ethanol extract showed maximum TPC (0.126 mg/g, gallic acid equivalent in dry sample), TFC (0.094 mg/g, rutin equivalent in dry sample) and TTC (29.32 mg/g, catechin equivalent in dry sample), as well as antioxidant and anti-inflammatory properties. Chloroform extract exhibited the strongest cytotoxicity against the human breast cancer cell line, MCF-7. GC/MS analysis revealed the presence of 90 different phytoconstituents among the extracts. Antioxidant and anti-inflammatory activities had a positive correlation with TPC, TFC and TTC. However, the anticancer activity showed a negative correlation with TPC, TFC and TTC. From the present study, it can be concluded that P. verticillatum possessed remarkable antioxidant, anti-inflammatory, and anticancer activities, which could be due to different secondary metabolites of the plant. Phenolic compounds are likely responsible for antioxidant and anti-inflammatory activities. However, flavonoids and other compounds might contribute to the anticancer potential of the plant. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Balancing Antioxidant, Hypolipidemic and Anti-inflammatory Activity in a Single Agent: The Example of 2-Hydroxy-2-Substituted Morpholine, 1,4-Benzoxazine and 1,4-Benzothiazine Derivatives as a Rational Therapeutic Approach against Atherosclerosis.

PubMed

Matralis, Alexios N; Bavavea, Eugenia-Ismini; Incerpi, Sandra; Pedersen, Jens Z; Kourounakis, Angeliki P

2017-01-01

In line with our previous studies, novel morpholine and benzoxa(or thia)zine lead compounds have been developed through a rational design that modulate a multiplicity of targets against atherosclerosis. We have evaluated the most promising compounds for their efficiency to a) intercept and scavenge free radicals, b) inhibit the metal ion (Cu2+)- induced LDL oxidation c) act intracellularly as antioxidants in THP-1 monocytes from a leukemic patient and d) inhibit the pro-inflammatory enzymes cyclooxygenase-1 (COX-1) and -2 (COX-2) in vitro. Furthermore, two representative compounds were tested for their potential to decrease lipidemic parameters (TC, LDL and TG) in hyperlipidemic mice. Most derivatives indicated a remarkable antioxidant activity, while at the same time exhibited a significant in vitro anti-inflammatory activity, inhibiting COX-1 or/and COX-2 activity at 20 μΜ. In addition, after their long-term administration, compounds 6 and 8 afforded considerable activity in a chronic experimental animal model of hyperlipidemia (after high fat diet administration). The multifunctional pharmacological profile exhibited by the compounds of this study renders them interesting lead compounds for the development of novel agents against atherosclerosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Shikonin exerts anti-inflammatory effects in a murine model of lipopolysaccharide-induced acute lung injury by inhibiting the nuclear factor-kappaB signaling pathway.

PubMed

Liang, Dejie; Sun, Yong; Shen, Yongbin; Li, Fengyang; Song, Xiaojing; Zhou, Ershun; Zhao, Fuyi; Liu, Zhicheng; Fu, Yunhe; Guo, Mengyao; Zhang, Naisheng; Yang, Zhengtao; Cao, Yongguo

2013-08-01

Shikonin, an analog of naphthoquinone pigments isolated from the root of Lithospermum erythrorhyzon, was recently reported to exert beneficial anti-inflammatory effects both in vivo and in vitro. The present study aimed to investigate the potential therapeutic effect of shikonin in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Dexamethasone was used as a positive control to evaluate the anti-inflammatory effect of shikonin in the study. Pretreatment with shikonin (intraperitoneal injection) significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, shikonin significantly reduced the concentrations of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid induced by LPS. Compared with the LPS group, lung histopathologic changes were less pronounced in the shikonin-pretreated mice. Additionally, Western blotting results showed that shikonin efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that shikonin exerts anti-inflammatory properties in LPS-mediated ALI, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. Shikonin may be a potential agent for the prophylaxis of ALI. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Metastasis

DTIC Science & Technology

2010-10-01

Task 3. To determine the effect of anti -inflammatory treatment on VEGFR-3 expression, tumor lymphangiogenesis, lymphatic metastasis, and spread to...breast carcinoma line MDA-MB-231 into the MFP of CB-17 SCID mice and treat them with NF-κB targeting anti -inflammatory drugs, PDTC and dexamethasone...model of human breast cancer is significantly enhanced by concurrent anti -VEGF-A therapy. Neoplasia. 2008 Jun;10(6):613-23. Awards/Presentations

Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

PubMed

Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

2016-02-01

Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases.

Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-{kappa}B, p38MAPK and Akt inhibition

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

Essafi-Benkhadir, Khadija; Refai, Amira; Riahi, Ichrak

Highlights: Black-Right-Pointing-Pointer Quince peel polyphenols inhibit LPS-induced secretion of TNF-{alpha} and IL-8. Black-Right-Pointing-Pointer Quince peel polyphenols augment LPS-induced secretion of IL-10 and IL-6. Black-Right-Pointing-Pointer Quince peel polyphenols-mediated inhibition of LPS-induced secretion of TNF-{alpha} is partially mediated by IL-6. Black-Right-Pointing-Pointer The anti-inflammatory effects of quince polyphenols pass through NF-{kappa}B, p38MAPK and Akt inhibition. -- Abstract: Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effectmore » of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-{alpha} and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-{alpha} secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-{kappa}B), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince-rich regimen may help to prevent and improve the treatment of such diseases.« less

Anti-inflammatory effects of fimasartan via Akt, ERK, and NFκB pathways on astrocytes stimulated by hemolysate.

PubMed

Yang, Xiu-Li; Kim, Chi Kyung; Kim, Tae Jung; Sun, Jing; Rim, Doeun; Kim, Young-Ju; Ko, Sang-Bae; Jang, Hyunduk; Yoon, Byung-Woo

2016-02-01

The aim of this study was to investigate whether fimasartan, a novel angiotensin II receptor blocker, modulates hemolysate-induced inflammation in astrocytes. We stimulated astrocytes with hemolysate to induce hemorrhagic inflammation in vitro. Astrocytes were pretreated with fimasartan and then incubated with hemolysate at different durations. Anti-inflammatory cell signaling molecules including Akt, extracellular signal regulated kinase (ERK), NFκB and cyclooxygenase-2 (COX-2) were assessed by western blotting. Pro-inflammatory mediators were evaluated by real-time RT-PCR and ELISA. The stimulation by hemolysate generated a robust activation of inflammatory signaling pathways in astrocytes. Hemolysate increased the phosphorylation of Akt at 1 h, and ERK1/2 at 20 min compared with the control group and promoted the degradation of IκBα. Pretreated fimasartan significantly decreased hemolysate-induced phosphorylation of Akt and ERK1/2. In addition, fimasartan also suppressed NFκB-related inflammatory pathways induced by hemolysate, including reduction of the gene expression of NFκB, and decreased nuclear translocation of NFκB and degradation of IκB. This reduction of inflammatory upstream pathways decreased the expression of inflammatory end-products: COX-2 and interleukin-1 (IL-1β). Furthermore, the expression of COX-2 was attenuated by both Akt inhibitor (LY294002) and ERK inhibitor (U0126), and IκBα degradation was suppressed by LY294002. These results demonstrate that pretreatment with fimasartan to astrocytes suppresses the inflammatory responses induced by hemolysate. Akt, ERK and NFκB were associated with hemolysate-induced COX-2 and IL-1β expression. Based on these mechanisms, fimasartan could be a candidate anti-inflammatory regulator for the treatment of intracerebral hemorrhage.

Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

PubMed Central

Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

2016-01-01

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

Pharmacological evaluation for anti-asthmatic and anti-inflammatory potential of Woodfordia fruticosa flower extracts.

PubMed

Hiralal Ghante, Mahavir; Bhusari, Kishore P; Duragkar, Nandkishore J; Ghiware, Nitin B

2014-07-01

Woodfordia fruticosa Kurz. (Lythraceae) flowers are ethnopharmacologically acclaimed in the Indian medicinal system to treat asthma. To evaluate W. fruticosa flower extracts for anti-asthmatic effect. Ethyl acetate, acetone, methanol, and hydro-alcohol extracts of W. fruticosa flowers were obtained successively and standardized. Ability of extracts to stabilize free radicals and compound-48/80-induced mast cell degranulation was evaluated. In vitro anti-inflammatory potential of extracts at 100 and 200 µg/ml by membrane stabilization and in vivo inhibition of rat paw edema up to 5 h (100 and 200 mg/ml; p.o.) was evaluated. In vitro bronchorelaxant effect was examined against histamine- and acetylcholine (1 µg/ml; independently)-induced guinea pig tracheal contraction. Extracts were evaluated for bronchoprotection (in vivo) ability against 0.1% histamine- and 2% acetylcholine-induced bronchospasm in guinea pigs at 100 and 200 mg/ml; p.o. Standardization studies revealed that the methanol extract exhibited highest polyphenolic (62.66 GAE), and flavonoid (6.32 RE) content and HPLC fingerprinting confirmed the presence of gallic acid (Rt 1.383). IC50 values for DPPH scavenging and metal chelation by the methanol extract were 40.42 and 31.50 µg/ml. Methanol and ethyl acetate extracts at 100 µg/ml exhibited 06.52 and 07.12% of histamine release. Methanol, ethyl acetate, and hydro alcohol extracts at 200 mg/kg demonstrated 32.73, 29.83, 26.75% and 32.46, 9.38, 26.75% inhibition of egg albumin and carrageenan-induced inflammation, respectively. Methanol extract exhibited 100% bronchorelaxation and 48.83% bronchoprotection. Woodfordia fruticosa flower (WFF) extracts exhibited anti-asthmatic effect by demonstrating bronchoprotection, bronchorelaxation, anti-inflammatory, antioxidant, and mast cell stabilization ability.

Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti-inflammatory, antioxidant and molecular docking studies.

PubMed

Honmore, Varsha S; Kandhare, Amit D; Kadam, Parag P; Khedkar, Vijay M; Sarkar, Dhiman; Bodhankar, Subhash L; Zanwar, Anand A; Rojatkar, Supada R; Natu, Arun D

2016-04-01

Inflammation triggered by oxidative stress can cause various ailments, such as cancer, rheumatoid arthritis, asthma, diabetes etc. In the last few years, there has been a renewed interest in studying the antioxidant and anti-inflammatory action of plant constituents such as flavonoids and diarylheptanoids. To evaluate the antioxidant, anti-inflammatory activity and the total phenolic content of isolated compounds from Alpinia officinarum rhizomes. Furthermore, molecular docking was performed to study the binding mode of these compounds into the active site of cyclooxygenase-2 (COX-2). A. officinarum rhizomes were extracted by maceration, using methanol. This extract was further fractionated by partitioning with hexane, chloroform and ethyl acetate and these fractions on further purification resulted in isolation of five pure compounds. Characterization was carried out by using (1)H NMR, (13)C NMR and MS. They were further evaluated for antioxidant and anti-inflammatory activity using carrageenan-induced paw edema model in rats. Molecular docking study was performed using Glide module integrated in Schrodinger molecular modeling software. The compounds were identified as 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 3,5,7-trihydroxyflavone (Galangin, 3), 3,5,7-trihydroxy-4'-methoxyflavone (Kaempferide, 4) and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone (5). The compound-3 and compound-5 (10mg/kg) showed significant (p<0.001) antioxidant and anti-inflammatory potential. Moreover, total phenolic content was detected as 72.96 mg and 51.18 mg gallic acid equivalent respectively. All the five isolates were found to be good binders with COX-2 (average docking score -9.03). Galangin and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone exhibited anti-inflammatory and in-vitro antioxidant activity which may be due to presence of phenolic content in it. The molecular docking study revealed that these compounds have affinity towards COX-2 active site which can further be explored as selective COX-2 inhibitors. The results obtained in this work justify the use of A. officinarum in the treatment of inflammatory disorders like rheumatoid arthritis and inflammatory bowel diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Tamarixetin Exhibits Anti-inflammatory Activity and Prevents Bacterial Sepsis by Increasing IL-10 Production.

PubMed

Park, Hee Jo; Lee, Seung Jun; Cho, Joon; Gharbi, Amal; Han, Hee Dong; Kang, Tae Heung; Kim, Yangmee; Lee, Yeongjoon; Park, Won Sun; Jung, In Duk; Park, Yeong-Min

2018-06-22

Sepsis is a systemic inflammatory response to pathogenic infection that currently has no specific pharmaceutical interventions. Instead, antibiotics administration is considered the best available option, despite increasing drug resistance. Alternative strategies are therefore urgently required to prevent sepsis and strengthen the host immune system. One such option is tamarixetin (4'- O-methylquercetin), a naturally occurring flavonoid derivative of quercetin that protects against inflammation. The purpose of this study was to determine whether the anti-inflammatory effects of tamarixetin protect against the specific inflammatory conditions induced in lipopolysaccharide (LPS) or Escherichia coli K1 models of sepsis. Our study showed that tamarixetin reduced the secretion of various inflammatory cytokines by dendritic cells after activation with LPS. It also promoted the secretion of the anti-inflammatory cytokine interleukin (IL)-10 and specifically increased the population of IL-10-secreting immune cells in LPS-activated splenocytes. Tamarixetin showed general anti-inflammatory effects in mouse models of bacterial sepsis and decreased bacteria abundance and endotoxin levels. We therefore conclude that tamarixetin has superior anti-inflammatory properties than quercetin during bacterial sepsis. This effect is associated with an increased population of IL-10-secreting immune cells and suggests that tamarixetin could serve as a specific pharmaceutical option to prevent bacterial sepsis.

Molecular mechanism of action of Pelargonidin-3-O-glucoside, the main anthocyanin responsible for the anti-inflammatory effect of strawberry fruits.

PubMed

Duarte, Larissa Jeremias; Chaves, Vitor Clasen; Nascimento, Marcus Vinicius Pereira Dos Santos; Calvete, Eunice; Li, Mingchuan; Ciraolo, Elisa; Ghigo, Alessandra; Hirsch, Emilio; Simões, Claudia Maria Oliveira; Reginatto, Flávio Henrique; Dalmarco, Eduardo M

2018-05-01

Fragaria x ananassa Duch., popularly called strawberry, is known for its worldwide consumption and important biological activities, and these effects are related to its high concentration of anthocyanins. Pelargonidin-3-O-glucoside (P3G) is a major anthocyanin found in strawberry, and was evaluated for its anti-inflammatory action in experimental models. The effect of strawberry extract and P3G, on leukocyte migration, exudation levels and many inflammatory mediators, was therefore evaluated in an in vivo model. An in vitro study was also carried out to characterize the effect of P3G on mitogen-activated protein kinases, and on nuclear transcript factors NF-κB and AP-1. The results revealed that the strawberry and P3G have important anti-inflammatory proprieties, and the anti-inflammatory mechanism of P3G involves the arrest of IkB-α activation and reduction in JNK MAPK phosphorylation. The results reinforce that strawberry fruits are functional foods that can act as an adjuvant in the treatment of inflammatory conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.

PubMed

El-Hawash, Soad A M; Soliman, Raafat; Youssef, Amal M; Ragab, Hanan M A; Elzahhar, Perihan A S; El-Ashmawey, Ibrahim M; Abdel Wahab, Abeer E; Shaat, Iman A

2014-05-01

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.

The melanogenesis-inhibitory, anti-inflammatory, and chemopreventive effects of limonoids in n-hexane extract of Azadirachta indica A. Juss. (neem) seeds.

PubMed

Akihisa, Toshihiro; Takahashi, Akitomo; Kikuchi, Takashi; Takagi, Mio; Watanabe, Kensuke; Fukatsu, Makoto; Fujita, Yukiko; Banno, Norihiro; Tokuda, Harukuni; Yasukawa, Ken

2011-01-01

Seventeen limonoids (tetranortriterpenoids 1-17) were isolated from the n-hexane extract of Azadirachta indica (neem) seeds. The previously unidentified compound 16 was established by spectroscopy to be 17-defurano-17-oxosalannin. The effects of six compounds, 6 and 11-15, on melanogenesis in B16 melanoma cells was evaluated; 2 compounds, salannin (13) and 3-deacetylsalannin (15), exhibited marked inhibitory effects (70-74% reduction of melanin content at 25 µg/mL) with only minor cytotoxicity (79-85% of cell viability). Eleven compounds, 2, 3, 5, 6, and 9-15, were evaluated for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1.7 nmol/ear) in mice; all exhibited marked anti-inflammatory activity (ID(50) values 0.22-0.57 µmol/ear). In addition, compounds 6 and 11-16 exerted moderate inhibition (IC(50) values of 410-471 mol ratio/32 pmol TPA) of TPA-induced Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells. The triacylglycerol fraction of the n-hexane extract contained oleic acid (50.2%) as the most predominant fatty acid constituent.

Large-scale bioprospecting of cyanobacteria, micro- and macroalgae from the Aegean Sea.

PubMed

Montalvão, Sofia; Demirel, Zeliha; Devi, Prabha; Lombardi, Valter; Hongisto, Vesa; Perälä, Merja; Hattara, Johannes; Imamoglu, Esra; Tilvi, Supriya Shet; Turan, Gamze; Dalay, Meltem Conk; Tammela, Päivi

2016-05-25

Marine organisms constitute approximately one-half of the total global biodiversity, being rich reservoirs of structurally diverse biofunctional components. The potential of cyanobacteria, micro- and macroalgae as sources of antimicrobial, antitumoral, anti-inflammatory, and anticoagulant compounds has been reported extensively. Nonetheless, biological activities of marine fauna and flora of the Aegean Sea have remained poorly studied when in comparison to other areas of the Mediterranean Sea. In this study, we screened the antimicrobial, antifouling, anti-inflammatory and anticancer potential of in total 98 specimens collected from the Aegean Sea. Ethanol extract of diatom Amphora cf capitellata showed the most promising antimicrobial results against Candida albicans while the extract of diatom Nitzschia communis showed effective results against Gram-positive bacterium, S. aureus. Extracts from the red alga Laurencia papillosa and from three Cystoseira species exhibited selective antiproliferative activity against cancer cell lines and an extract from the brown alga Dilophus fasciola showed the highest anti-inflammatory activity as measured in primary microglial and astrocyte cell cultures as well as by the reduction of proinflammatory cytokines. In summary, our study demonstrates that the Aegean Sea is a rich source of species that possess interesting potential for developing industrial applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Intestinal anti-inflammatory effects of goat whey on DNBS-induced colitis in mice

PubMed Central

Araújo, Daline F. S.; Guerra, Gerlane C. B.; Pintado, Maria Manuela E.; Sousa, Yasmim R. F.; Algieri, Francesca; Rodriguez-Nogales, Alba; Araújo, Raimundo F.; Gálvez, Julio; Queiroga, Rita de Cássia R. E.; Rodriguez-Cabezas, Maria Elena

2017-01-01

This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-κB p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1β, IL-6, IL-17, TNF-α, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited anti-inflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD. PMID:28957373

Intestinal anti-inflammatory effects of goat whey on DNBS-induced colitis in mice.

PubMed

Araújo, Daline F S; Guerra, Gerlane C B; Pintado, Maria Manuela E; Sousa, Yasmim R F; Algieri, Francesca; Rodriguez-Nogales, Alba; Araújo, Raimundo F; Gálvez, Julio; Queiroga, Rita de Cássia R E; Rodriguez-Cabezas, Maria Elena

2017-01-01

This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-κB p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1β, IL-6, IL-17, TNF-α, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited anti-inflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD.

Corydalis bungeana Turcz. attenuates LPS-induced inflammatory responses via the suppression of NF-κB signaling pathway in vitro and in vivo.

PubMed

Zhai, Xiao-Ting; Chen, Jia-Quan; Jiang, Cui-Hua; Song, Jie; Li, Dong-Yu; Zhang, Hao; Jia, Xiao-Bin; Tan, Wei; Wang, Shu-Xia; Yang, Yi; Zhu, Fen-Xia

2016-12-24

Corydalis bungeana Turcz. (C. bungeana) is one of traditionally used medicines in China and possesses various biological effects, such as anti-inflammatory, antibacterial activity and inhibition of the immune function of the host. we studied the anti-inflammatory effect and molecular mechanism involved of C. bungeana both in vitro and in vivo model system in which the inflammatory response was induced by LPS treatment. Anti-inflammatory activity of C. bungeana was investigated by LPS-induced RAW 264.7 macrophages and BALB/c mice. The production and expression of pro-inflammatory cytokines were evaluated by Griess reagent, ELISA kits and RT-qPCR, respectively. Phosphorylation status of IκBα and p65 was illustrated by western blot assay. C. bungeana reduced the secretion of NO, TNF-α, IL-6 and IL-1β through inhibiting the protein expression of iNOS, TNF-α, IL-6 and IL-1β in vitro and in vivo. Western blot analysis suggested that C. bungeana supressed NF-κB activation via regulating the phosphorylation of IκBα and p65. Immunohistochemical assay also demostrated the histological inflammatory change in liver tissue. The results indicate that C. bungeana supresses the activation of NF-κB signaling pathway through inhibiting phosphorylation of IκBα and p65, which results in good anti-inflammatory effect. In addition, C. bungeana attenuates inflammatory reaction by supressing the expression of various inflammatory cytokines both in vivo and in vitro. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

PubMed

Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

2014-07-15

Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa.

6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ

PubMed Central

Han, Qinghe; Yuan, Qinghai; Meng, Xiaolin; Huo, Junyuan; Bao, Yuxin; Xie, Guanghong

2017-01-01

6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been known to have anti-tumor and anti-inflammatory effects. However, the anti-inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2 microglia remains largely unknown. In this study, we evaluated the anti-inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was administrated 1 h before LPS treatment. The production of inflammatory mediators were detected by ELISA. The expression of NF-κB and PPAR-γ were detected by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 production in a concentration dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-κB activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. In addition, 6-Shogaol could increase the expression of PPAR-γ. Moreover, inhibition of PPAR-γ by GW9662 could prevent the inhibition of 6-Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol inhibits LPS-induced inflammation by activating PPAR-γ. PMID:28410218

Curcumin Suppresses T Cell Activation by Blocking Ca2+ Mobilization and Nuclear Factor of Activated T Cells (NFAT) Activation

PubMed Central

Kliem, Christian; Merling, Anette; Giaisi, Marco; Köhler, Rebecca; Krammer, Peter H.; Li-Weber, Min

2012-01-01

Curcumin is the active ingredient of the spice turmeric and has been shown to have a number of pharmacologic and therapeutic activities including antioxidant, anti-microbial, anti-inflammatory, and anti-carcinogenic properties. The anti-inflammatory effects of curcumin have primarily been attributed to its inhibitory effect on NF-κB activity due to redox regulation. In this study, we show that curcumin is an immunosuppressive phytochemical that blocks T cell-activation-induced Ca2+ mobilization with IC50 = ∼12.5 μm and thereby prevents NFAT activation and NFAT-regulated cytokine expression. This finding provides a new mechanism for curcumin-mediated anti-inflammatory and immunosuppressive function. We also show that curcumin can synergize with CsA to enhance immunosuppressive activity because of different inhibitory mechanisms. Furthermore, because Ca2+ is also the secondary messenger crucial for the TCR-induced NF-κB signaling pathway, our finding also provides another mechanism by which curcumin suppresses NF-κB activation. PMID:22303019

Nematode Peptides with Host-Directed Anti-inflammatory Activity Rescue Caenorhabditis elegans from a Burkholderia pseudomallei Infection.

PubMed

Lim, Mei-Perng; Firdaus-Raih, Mohd; Nathan, Sheila

2016-01-01

Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs) have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi)-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8× MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators.

Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model.

PubMed

Moon, Dong-Oh; Kim, Mun-Ok; Choi, Yung Hyun; Park, Yung-Min; Kim, Gi-Young

2010-05-01

Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities. The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs). DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness. In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production. Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed. The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum. Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses. Copyright 2010 Elsevier B.V. All rights reserved.

Downregulation of matrix metalloproteinase-13 by the root extract of Cyathula officinalis Kuan and its constituents in IL-1β-treated chondrocytes.

PubMed

Park, Hyun Young; Lim, Hyun; Kim, Hyun Pyo; Kwon, Yong Soo

2011-09-01

The roots of Cyathula officinalis Kuan are widely used in Chinese medicine for the treatment of inflammatory disorders. Here, the ability of C. officinalis Kuan to downregulate matrix metalloproteinase (MMP)-13 was examined since MMP-13 is an important enzyme for the degradation of the cartilage collagen matrix, especially under arthritic conditions. The ethanol extract of C. officinalis Kuan as well as the N-hexane and chloroform soluble fractions were found to potently inhibit MMP-13 induction in IL-1 β-treated SW1353 cells, a human chondrosarcoma cell line, at 50-200 µg/mL. Activity-guided separation led to the isolation of six compounds, palmitic acid (1), β-sitosterol (2), α-spinasterol (3), atractylenolide I (4), 1,3-diacetoxy-tetradeca-6E,12E-dien-8,10-dyn (5), and N-trans-feruloyl-3-methyldopamine (6). Among these, 4 and 5 exhibited MMP-13 downregulating activity in IL-1 β-treated SW1353 cells. And 4 also showed anti-oedematous activity against λ-carageenan-induced paw edema in mice at 20-200 mg/kg, p. o. The results of this study provide information that can help elucidate the action mechanism of C. officinalis Kuan. In addition, the results presented here suggest that C. officinalis Kuan and its constituents may have the potential for chondroprotection against cartilage degrading disorders. © Georg Thieme Verlag KG Stuttgart · New York.

Inhibitory effects of the methylene chloride fraction of JP05 on the production of inflammatory mediators in LPS-activated BV2 microglia.

PubMed

Jung, Hyo Won; Oh, Tae Woo; Jung, Jin Ki; Lee, Je-Hyun; Shin, Gil Jo; Park, Yong-Ki

2012-02-01

Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines from activated microglia in the central nervous system contributes to uncontrolled inflammation in neurodegenerative disorders. In this study, we investigated the anti-inflammatory activities of the methylene chloride fraction of JP05 (JP05-MC) on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells, and its mechanism of action. JP05-MC significantly inhibited LPS-induced production of NO and the proinflammatory cytokines, TNF-α and IL-6, in BV2 cells. JP05-MC also attenuated the mRNA expression and protein levels of inducible nitric oxide synthase in LPS-induced BV2 cells. JP05-MC significantly attenuated LPS-elicited phosphorylation of the mitogen-activated protein kinase (MAPK), extracellular-signal-regulated kinase 1/2, and nuclear factor-κB (NF-κB) nuclear translocation in BV2 cells. Our results indicate that JP05-MC exerts anti-inflammatory properties via downregulation of inflammatory mediator gene transcription by suppressing the MAPK and NF-κB pathways, suggesting that JP05-MC may have therapeutic potential as an anti-inflammatory agent in neurodegenerative diseases.

Downregulation of the glucocorticoid-induced leucine zipper (GILZ) promotes vascular inflammation.

PubMed

Hahn, Rebecca T; Hoppstädter, Jessica; Hirschfelder, Kerstin; Hachenthal, Nina; Diesel, Britta; Kessler, Sonja M; Huwer, Hanno; Kiemer, Alexandra K

2014-06-01

Glucocorticoid-induced leucine zipper (GILZ) represents an anti-inflammatory mediator, whose downregulation has been described in various inflammatory processes. Aim of our study was to decipher the regulation of GILZ in vascular inflammation. Degenerated aortocoronary saphenous vein bypass grafts (n = 15), which exhibited inflammatory cell activation as determined by enhanced monocyte chemoattractrant protein 1 (MCP-1, CCL2) and Toll-like receptor 2 (TLR2) expression, showed significantly diminished GILZ protein and mRNA levels compared to healthy veins (n = 23). GILZ was also downregulated in human umbilical vein endothelial cells (HUVEC) and macrophages upon treatment with the inflammatory cytokine TNF-α in a tristetraprolin (ZFP36, TTP)- and p38 MAPK-dependent manner. To assess the functional implications of decreased GILZ expression, we determined NF-κB activation after GILZ knockdown by siRNA and found that NF-κB activity and inflammatory gene expression were significantly enhanced. Importantly, ZFP36 is induced in TNF-α-activated HUVEC as well as in degenerated vein bypasses. When atheroprotective laminar shear stress was employed, GILZ levels in HUVEC increased on mRNA and protein level. Laminar flow also counteracted TNF-α-induced ZFP36 expression and GILZ downregulation. MAP kinase phosphatase 1 (MKP-1, DUSP1), a negative regulator of ZFP36 expression, was distinctly upregulated under laminar shear stress conditions and downregulated in degenerated vein bypasses. Our data show a diminished expression of the anti-inflammatory mediator GILZ in the inflamed vasculature and indicate that GILZ downregulation requires the mRNA binding protein ZFP36. We suggest that reduced GILZ levels play a role in cardiovascular disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chondroitin-6-sulfate attenuates inflammatory responses in murine macrophages via suppression of NF-κB nuclear translocation.

PubMed

Tan, Guak-Kim; Tabata, Yasuhiko

2014-06-01

Inflammation is a host protective response to noxious stimuli, and excessive production of pro-inflammatory mediators by macrophages (mφ) can lead to numerous pathological conditions. In this study, immunomodulatory effects of immobilized and soluble glycosaminoglycans (GAGs) on mouse-bone-marrow-derived mφ were compared by measuring nitric oxide (NO). We demonstrate here that all GAGs studied except for heparin were able to modulate interferon-γ/lipopolysaccharide (IFN-γ/LPS)-induced NO release by mφ to varying extents after 24h of incubation. In particular, the modulatory activities of soluble chondroitin-6-sulfate (C6S), hyaluronic acid and heparan sulfate altered markedly after covalent immobilization. Of these, soluble C6S exhibited the strongest NO inhibitory activity, and the inhibition was dose- and time-dependent. Moreover, C6S significantly reduced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α production by IFN-γ/LPS- or LPS-activated mφ. Specifically, the C6S-mediated suppression of mφ pro-inflammatory phenotype was accompanied by an increase in the IL-10 level, suggesting a possible switch towards anti-inflammatory/wound healing M2 state. In addition, the highest magnitude of inhibitory effects was obtained when cells were pre-treated with C6S prior to IFN-γ/LPS or LPS challenge, suggesting an additional role for C6S in protection against microbial infection. Further investigations reveal that the anti-inflammatory effects of C6S on activated mφ may be ascribed at least in part to suppression of NF-κB nuclear translocation. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of allylated and prenylated mono-carbonyl analogs of curcumin as anti-inflammatory agents.

PubMed

Liu, Zhiguo; Tang, Longguang; Zou, Peng; Zhang, Yali; Wang, Zhe; Fang, Qilu; Jiang, Lili; Chen, Gaozhi; Xu, Zheng; Zhang, Huajie; Liang, Guang

2014-03-03

Curcumin has been shown to possess anti-inflammatory activities but has been limited for its low stability and poor bioavailability. We have previously reported four series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MACs). In continuation of our ongoing research, we designed and synthesized 33 novel allylated or prenylated MACs here, and evaluated their anti-inflammatory effects in RAW 264.7 macrophages. A majority of them effectively inhibited the LPS-induced expression of TNF-α and IL-6, especially IL-6. The preliminary SAR and quantitative SAR analysis were conducted. Compound 14q is the most potent analog among them, and exhibits significant protection against LPS-induced death in septic mice. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Apo-9′-Fucoxanthinone, Isolated from Sargassum muticum, Inhibits CpG-Induced Inflammatory Response by Attenuating the Mitogen-Activated Protein Kinase Pathway

PubMed Central

Chae, Doobyeong; Manzoor, Zahid; Kim, Sung Chun; Kim, Sohyun; Oh, Tae-Heon; Yoo, Eun-Sook; Kang, Hee-Kyoung; Hyun, Jin-Won; Lee, Nam Ho; Ko, Mi-Hee; Koh, Young-Sang

2013-01-01

Sargassum muticum (S. muticum) is a brown edible alga and widely distributed in Korea. This report was designed to evaluate the anti-inflammatory properties of apo-9′-fucoxanthinone (APO-9′) isolated from S. muticum on pro-inflammatory cytokine production. S. muticum extract (SME) exhibited significant inhibitory effects on pro-inflammatory cytokine production in bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs). APO-9′ pre-treatment in the CpG DNA-stimulated BMDMs and BMDCs showed a strong dose-dependent inhibitory effect on interleukin (IL)-12 p40, IL-6 and tumor necrosis factor (TNF)-α production with IC50 values ranging from 5.31 to 13.79. It exhibited a strong inhibitory effect on the phosphorylation of ERK1/2 and on activator protein (AP)-1 reporter activity. APO-9′ pre-treatment exhibited significant inhibition of CpG DNA-induced production of inducible nitric oxide synthase. Taken together, these data suggest that SME and APO-9′ have a significant anti-inflammatory property and warrant further studies concerning the potentials of SME and APO-9′ for medicinal use. PMID:23985898

Possible Contribution of Zerumbone-Induced Proteo-Stress to Its Anti-Inflammatory Functions via the Activation of Heat Shock Factor 1.

PubMed

Igarashi, Yoko; Ohnishi, Kohta; Irie, Kazuhiro; Murakami, Akira

2016-01-01

Zerumbone is a sesquiterpene present in Zinger zerumbet. Many studies have demonstrated its marked anti-inflammatory and anti-carcinogenesis activities. Recently, we showed that zerumbone binds to numerous proteins with scant selectivity and induces the expression of heat shock proteins (HSPs) in hepatocytes. To dampen proteo-toxic stress, organisms have a stress-responsive molecular machinery, known as heat shock response. Heat shock factor 1 (HSF1) plays a key role in this protein quality control system by promoting activation of HSPs. In this study, we investigated whether zerumbone-induced HSF1 activation contributes to its anti-inflammatory functions in stimulated macrophages. Our findings showed that zerumbone increased cellular protein aggregates and promoted nuclear translocation of HSF1 for HSP expression. Interestingly, HSF1 down-regulation attenuated the suppressive effects of zerumbone on mRNA and protein expressions of pro-inflammatory genes, including inducible nitric oxide synthase and interlukin-1β. These results suggest that proteo-stress induced by zerumbone activates HSF1 for exhibiting its anti-inflammatory functions.

Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K, ERK and NF-kappaB activation.

PubMed

Kim, Won-Jung; Lee, Min-Young; Kim, Jung-Hee; Suk, Kyoungho; Lee, Won-Ha

2010-10-01

Inflammation is known to be closely associated with the development of cancer. Decursinol angelate (DA), a coumarin compound isolated from Angelica gigas and related compounds have been shown to possess potent anti-inflammatory activities. However, little is known about their effects on the inflammatory processes associated with cancer. In this study, the anti-inflammatory effect of DA was evaluated in cancer cell lines with respect to cellular invasion through the extracellular matrix (ECM) and the expression of pro-inflammatory mediators such as cytokine, cell adhesion molecules and matrix metalloproteinase (MMP)-9. DA inhibited the invasion of fibrosarcoma cell line, HT1080 and breast cancer cell line, MDA-MB-231 in the Matrigel invasion assay. DA-mediated suppression of cancer cell invasion was accomplished by suppression of PI3K activity known to be associated with cytoskeletal rearrangement related to cellular migration. DA also suppressed the adhesion of cancer cells to ECM mediated by down-regulation of beta(1)-integrin expression levels. Furthermore, DA inhibited the expression of pro-inflammatory cytokines and MMP-9 through suppression of PI3K, ERK and NF-kappaB activation. These results demonstrate that DA suppresses invasion and inflammatory activation of cancer cells through modulation of PI3K/AKT, ERK and NF-kappaB. These anti-inflammatory activities of DA may contribute to its anti-cancer activity. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Gentiolactone, a Secoiridoid Dilactone from Gentiana triflora, Inhibits TNF-α, iNOS and Cox-2 mRNA Expression and Blocks NF-κB Promoter Activity in Murine Macrophages

PubMed Central

Yamada, Hidetoshi; Kikuchi, Sayaka; Inui, Tomoki; Takahashi, Hideyuki; Kimura, Ken-ichi

2014-01-01

Background Gentian roots have been used as a herbal medicine because of their anti-inflammatory activities. However, the molecular mechanisms of these anti-inflammatory effects remain to be completely explained. Methods and Findings Here, we investigated anti-inflammatory effects of gentian roots and showed that root extracts from Gentiana triflora inhibited lipopolysaccharide (LPS)-induced expression of TNF-α in RAW264.7 cells. The extracts also contained swertiamarin and gentiopicroside, which are the major active compounds of gentian roots; however, neither compound had any effect on LPS-induced TNF-α production in our test system. We isolated gentiolactone as an inhibitor of TNF-α production from the extracts. Gentiolactone also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) expression at the mRNA level. Moreover, gentiolactone suppressed NF-κB transcriptional activity without inhibition of IκB degradation or NF-κB nuclear transport. Conclusions Our results indicate that inhibition of TNF-α, iNOS and Cox-2 expression by gentiolactone is one of the mechanisms of the anti-inflammatory properties of gentian roots. PMID:25423092

New Coumarin Derivatives as Potent Selective COX-2 Inhibitors: Synthesis, Anti-Inflammatory, QSAR, and Molecular Modeling Studies.

PubMed

Dawood, Dina H; Batran, Rasha Z; Farghaly, Thoraya A; Khedr, Mohammed A; Abdulla, Mohamed M

2015-12-01

Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti-inflammatory activities using the carrageenan-induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)-1 and COX-2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0-7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78 μM. The ethyl thiosemicarbazone 2b, thiazoline derivatives 3a, 3b, 5b, 6a, and 7f, and the thiazolidinone compounds 8b and 9a showed the highest in vivo and in vitro anti-inflammatory activities with remarkable COX-2 selectivity. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R(2) (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potential Anti-Inflammatory Treatment of Ischemic Heart Disease

PubMed Central

Hodzic, Enisa

2018-01-01

Introduction Ischemic heart disease (IHD) is clinical manifestation of chronic inflammatory progressive pathological process of atherosclerosis in coronary arteries. IHD is the leading cause of morbidity and mortality in the world. The question is whether it is possible to improve and direct the therapeutic treatment of IHD patients in the treatment of the inflammatory process in the atherosclerotic leasions. Material and Methods A prospective, comparative, analytica,clinically applicable, open-type study was performed. The study was conducted on 80 subjects with controlled biohumoral markers: troponin, CK, CK MB, BNP; markers of atherogenesis: LDL and homocystein; inflammatory markers: CRP, amyloid, cytokines IL-2, IL-6,TNF-alpha. The experimental group of 38 respondents had in addition to the conventional IHD treatment with: ampicillin (which included organosulfur compounds), cyancobalamin, vitamin B complex (B1, B2 and B6) and folacin. A control group of 42 respondents did not have this additional treatment. Results Major adverse cardic events (MACE) such as postinfarctic angina pectoris and repeated infarction, need for surgical interventions of myocardial revascularization, signs of cardiac insufficiency and death were observed during the one-year period. There was no correlation between the IL-2, IL-6 and TNF-alpha, as well as CK, CKMB and troponin and MACE in one-year follow-up. There was a strong positive correlation between MACE and CRP (p = 0,0002) and amyloid (p = 0,0005) as inflamatory markers; a strong positive correlation between MACE and homocysteine as an atherogenic marker (p = 0,0002, and amoderate positive correlation between MACE and BNP (p = 0.0403) as ischemic marker and marker of cardiac insufficiency. The echocardiographically monitored systolic function showed a moderate difference in the groups with average higher values in the experimantal group (p = 0.0282). Conclusion The applied treatment exhibited a moderate positive effect on the systolic function of LV and significantly reduced the MACE in the work compared to the control group (p <0.0001), and demonstrated a potential anti-inflammatory effect. PMID:29736096

Sulforaphane and its methylcarbonyl analogs inhibit the LPS-stimulated inflammatory response in human monocytes through modulating cytokine production, suppressing chemotactic migration and phagocytosis in a NF-κB- and MAPK-dependent manner.

PubMed

Reddy, Shridhivya A; Shelar, Sandeep B; Dang, Truong-Minh; Lee, Baxter Neng-Cun; Yang, Hong; Ong, Siew-Min; Ng, Hui-Li; Chui, Wai-Keung; Wong, Siew-Cheng; Chew, Eng-Hui

2015-02-01

Sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)-butane], an aliphatic isothiocyanate (ITC) naturally derived from cruciferous vegetables and largely known for its chemopreventive potential also appears to possess anti-inflammatory potential. In this study, structural analogs of SF {compound 1 [1-isothiocyanato-4-(methylcarbonyl)-butane] and 2 [1-isothiocyanato-3-(methylcarbonyl)-propane]} containing a carbonyl group in place of the sulfinyl group in SF, were evaluated for their anti-inflammatory activities. In RAW 264.7 cells, the ITCs at non-toxic concentrations caused an inhibition of NO and prostaglandin E2 (PGE2) release through suppressing expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as a reduction in matrix metalloproteinase-9 (MMP-9) expression, secretion and gelatinolytic activity. Further work performed on human monocytes isolated from blood of healthy donors revealed that the ITCs not only suppressed the expression and release of pro-inflammatory mediators IL-1β, IL-6, TNF-α and MMP-9, but also suppressed their antibody-independent phagocytic and chemotactic migratory abilities. These anti-inflammatory activities were mediated through suppression of the NF-κB and MAPK signaling pathways. In addition, the ITCs were revealed to interact with the cysteines in inhibitor of nuclear factor-κB kinase β subunit (IKKβ), which could contribute at least partly to the suppression of NF-κB signaling. In conclusion, results obtained in this study provide deeper insights into the anti-inflammatory properties of SF and its methylcarbonyl analogs and the underlying mechanisms. These compounds thus serve as promising candidates for clinical applications in controlling inflammatory conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

PubMed

Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

2013-12-01

Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

ANTI INFLAMMATORY ACTIVITY OF MORINGA OLIEFERA. LAM

PubMed Central

Rao, K.N. Venkataswera; Gopalakrishnan, V.; Loganathan, V.; Nathan, S. Shanmuganathan

1999-01-01

The aqueous and ethanolic (90%) extract of the leaves of M.Oliera Lam (Fam: Moringaceae) were studied for their anti inflammatory action in ale albino rats. Two extracts exhibited maximum action within two hours of challenge. The aqueous extract sowed significant (P<0.01) odema suppression similar to that of Ibuprofen at the first hour of carrageenan injection. The results confirms the folkers claim of the plant. PMID:22556890

LL-37-derived membrane-active FK-13 analogs possessing cell selectivity, anti-biofilm activity and synergy with chloramphenicol and anti-inflammatory activity.

PubMed

Rajasekaran, Ganesan; Kim, Eun Young; Shin, Song Yub

2017-05-01

Although the human-derived antimicrobial peptide (AMP) LL-37 has potent antimicrobial and anti-inflammatory activities, its therapeutic application is limited by its low cell selectivity and high production cost due to its large size. To overcome these problems, we tried to develop novel LL-37-derived short α-helical AMPs with improved cell selectivity and without a significant loss of anti-inflammatory activity relative to that of parental LL-37. Using amino acid substitution, we designed and synthesized a series of FK13 analogs based on the sequence of the 13-meric short FK13 peptide (residues 17-29 of LL-37) that has been identified as the region responsible for the antimicrobial activity of LL-37. Among the designed FK13 analogs, FK-13-a1 and FK-13-a7 showed high cell selectivity and retained the anti-inflammatory activity. The therapeutic index (a measure of cell selectivity) of FK-13-a1 and FK-13-a7 was 6.3- and 2.3-fold that of parental LL-37, respectively. Furthermore, FK-13-a1 and FK-13-a7 displayed more potent antimicrobial activity against antibiotic-resistant bacteria including MRSA, MDRPA, and VREF, than did LL-37. In addition, FK-13-a1 and FK-13-a7 exhibited greater synergistic effects with chloramphenicol against MRSA and MDRPA and were more effective anti-biofilm agents against MDRPA than LL-37 was. Moreover, FK-13-a1 and FK-13-a7 maintained their activities in the presence of physiological salts and human serum. SYTOX green uptake, membrane depolarization and killing kinetics revealed that FK13-a1 and FK13-a7 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Taken together, our results suggest that FK13-a1 and FK13-a7 can be developed as novel antimicrobial/anti-inflammatory agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives

PubMed Central

2012-01-01

Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases. PMID:24900565

Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives.

PubMed

Chen, Gaozhi; Liu, Zhiguo; Zhang, Yali; Shan, Xiaoou; Jiang, Lili; Zhao, Yunjie; He, Wenfei; Feng, Zhiguo; Yang, Shulin; Liang, Guang

2013-01-10

Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases.

Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-κB activation, and PPARγ modulation.

PubMed

Zeng, Huawu; Locatelli, Monica; Bardelli, Claudio; Amoruso, Angela; Coisson, Jean Daniel; Travaglia, Fabiano; Arlorio, Marco; Brunelleschi, Sandra

2011-05-25

There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison. Clovamide and rosmarinic acid inhibited PMA-induced O(2)(-) production and cytokine release (with a bell-shaped curve and maximal inhibition at 10-100 nM), as well as PMA-induced NF-κB activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome proliferator-activated receptor-γ (PPARγ) activity, which may exert anti-inflammatory effects. These findings indicate clovamide as a possible bioactive compound with anti-inflammatory activity in human cells.

Resveratrol inhibits LPS-induced mice mastitis through attenuating the MAPK and NF-κB signaling pathway.

PubMed

Zhang, Xu; Wang, Yanan; Xiao, Chong; Wei, Zhengkai; Wang, Jingjing; Yang, Zhengtao; Fu, Yunhe

2017-06-01

Resveratrol is a natural polyphenol extracted from mangy plants. It has been reported that resveratrol show multitudinous positive role in biology such as anti-oxidant, anti-nociception and anti-inflammatory effects. Therefore, the present study devotes to test the effect of resveratrol on LPS-induced mastitis in mice. Resveratrol was administered intraperitoneally 1 h before LPS treatment. And the anti-inflammatory effect of resveratrol was measured by histopathological examination, MPO assay, real-time PCR and western blotting analysis. The results showed that resveratrol significantly reduced the LPS-induced mammary histopathological changes. Meanwhile, it sharply attenuated the activity of MPO. The result also indicated that the resveratrol can decrease the expression of pro-inflammatory cytokines TNF-α and IL-1β. From the results of western blotting, resveratrol suppressed the expression of phosphorylation of p65 and IκB from NF-κB signal pathway and phosphorylation of p38 and ERK from MAPK signal pathway. These findings suggested that resveratrol may inhibit the inflammatory response in the mastitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis1

PubMed Central

Zhang, Qunzhou; Shi, Shihong; Liu, Yi; Uyanne, Jettie; Shi, Yufang; Shi, Songtao; Le, Anh D.

2010-01-01

Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-γ. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases. PMID:19923445

Rational Design and Synthesis of Biologically Active Disubstituted 2(3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents.

PubMed

Khokra, S L; Khan, S A; Choudhary, D; Hasan, S M; Ahmad, A; Husain, Asif

2016-01-01

Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery. A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies. The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug. Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

Nitroxide derivatives of non-steroidal anti-inflammatory drugs exert anti-inflammatory and superoxide dismutase scavenging properties in A459 cells.

PubMed

Flores-Santana, Wilmarie; Moody, Terry; Chen, Weibin; Gorczynski, Michael J; Shoman, Mai E; Velázquez, Carlos; Thetford, Angela; Mitchell, James B; Cherukuri, Murali K; King, S Bruce; Wink, David A

2012-02-01

Inflammation and reactive oxygen species are associated with the promotion of various cancers. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer prevention treatments has been promising in numerous cancers. We report the evaluation of NSAIDs chemically modified by the addition of a redox-active nitroxide group. TEMPO-aspirin (TEMPO-ASA) and TEMPO-indomethacin (TEMPO-IND) were synthesized and evaluated in the lung cancer cell line A549. We evaluated physico-chemical properties of TEMPO-ASA and TEMPO-IND by electron paramagnetic resonance and cyclic voltammetry. Superoxide dismutase-like properties was assayed by measuring cytochrome c reduction and anti-inflammatory effects were assayed by measuring production of prostaglandin E(2) (PGE(2) ) and leukotriene B(4) (LTB(4) ). MTT proliferation assay and clonogenic assay were evaluated in the A549 lung carcinoma cell line. Maximum tolerated doses (MTD) and acute ulcerogenic index were also evaluated in in vivo. MTD were: TEMPO (140 mg·kg(-1) ), ASA (100 mg·kg(-1) ), indomethacin (5 mg·kg(-1) ), TEMPO-ASA (100 mg·kg(-1) ) and TEMPO-IND (40 mg·kg(-1) ). While TEMPO-ASA was as well tolerated as ASA, TEMPO-IND showed an eightfold improvement over indomethacin. TEMPO-IND showed markedly less gastric toxicity than the parent NSAID. Both TEMPO-ASA and TEMPO-IND inhibited production of PGE(2) and LTB(4) in A549 cells with maximum effects at 100 µg·mL(-1) or 10 µg·mL(-1) respectively. The nitroxide-NSAIDs retained superoxide scavenging capacity of the parent nitroxide and anti-inflammatory effects, inhibiting cyclooxygenase and 5-lipoxygenase enzymes. These redox-modified NSAIDs might be potential drug candidates, as they exhibit the pharmacological properties of the parent NSAID with antioxidant activity decreasing NSAID-associated toxicity. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Estimation of total phenolic content, in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera

PubMed Central

Alhakmani, Fatma; Kumar, Sokindra; Khan, Shah Alam

2013-01-01

Objective To evaluate and compare the antioxidant potential and anti-inflammatory activity of ethanolic extract of flowers of Moringa oleifera (M. oleifera) grown in Oman. Methods Flowers of M. oleifera were collected in the month of December 2012 and identified by a botanist. Alcoholic extract of the dry pulverized flowers of M. oleifera were obtained by cold maceration method. The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods. Folin-Ciocalteu reagent was used to estimate total phenolic content. DPPH was used to determine in-vitro antioxidant activity and anti-inflammatory activity of flowers was investigated by protein denaturation method. Results Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins, alkaloids, flavonoids, cardiac glycosides etc. M. oleifera flowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity. The anti-inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium. Conclusions The results of our study suggest that flowers of M. oleifera possess potent anti-inflammatory activity and are also a good source of natural antioxidants. Further study is needed to identify the chemical compounds responsible for their anti-inflammatory activity. PMID:23905019

Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

PubMed

Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; da Silva, Josiane Mello; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira; Scio, Elita

2014-01-01

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

Dietary Phytosterols Protective Against Peptic Ulceration

PubMed Central

Tovey, Frank I; Capanoglu, Doga; Langley, G. John; Herniman, Julie M; Bor, Serhat; Ozutemiz, Omer; Hobsley, Michael; Bardhan, Karna Dev; Linclau, Bruno

2011-01-01

Background In developing countries the prevalence of duodenal ulceration is related to the staple diet and not to the prevalence of Helicobacter pylori. Experiments using animal peptic ulcer models show that the lipid fraction in foods from the staple diets of low prevalence areas gives protection against ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promotes healing of ulceration. The lipid from the pulse Dolichos biflorus (Horse gram) was highly active and used for further investigations. Further experiments showed the phospholipids, sterol esters and sterols present in Horse gram lipid were gastroprotective. Dietary phospholipids are known to be protective, but the nature of protective sterols in staple diets is not known. The present research investigates the nature of the protective phytosterols. Methods Sterol fractions were extracted from the lipid in Dolichos biflorus and tested for gastroprotection using the rat ethanol model. The fractions showing protective activity were isolated and identification of the components was investigated by Gas Chromatography-Mass Spectrometry (GC-MS). Results The protective phytosterol fraction was shown to consist of stigmasterol, β-sitosterol and a third as yet unidentified sterol, isomeric with β-sitosterol. Conclusions Dietary changes, affecting the intake of protective phospholipids and phytosterols, may reduce the prevalence of duodenal ulceration in areas of high prevalence and may reduce the incidence of recurrent duodenal ulceration after healing and elimination of Helicobacter pylori infection. A combination of phospholipids and phytosterols, such as found in the lipid fraction of ulceroprotecive foods, may be of value in giving protection against the ulcerogenic effect of NSAIDs. PMID:27942332

Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat.

PubMed

Akihisa, Toshihiro; Kojima, Nobuo; Kikuchi, Takashi; Yasukawa, Ken; Tokuda, Harukuni; T Masters, Eliot; Manosroi, Aranya; Manosroi, Jiradej

2010-01-01

Four triterpene acetates, alpha-amyrin acetate (1a), beta-amyrin acetate (2a), lupeol acetate (3a), and butyrospermol acetate (4a), and four triterpene cinnamates, alpha-amyrin cinnamate (1c), beta-amyrin cinnamate (2c), lupeol cinnamate (3c), and butyrospermol cinnamate (4c), were isolated from the kernel fat (n-hexane extract) of the shea tree (Vitellaria paradoxa; Sapotaceae). Upon evaluation of these eight triterpene esters for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds tested exhibited marked anti-inflammatory activity, with ID50 values in the range of 0.15-0.75 micromol/ear, and among which compound 3c showed the highest activity with ID(50) of 0.15 micromol/ear. Compound 3c (10 mg/kg) further exhibited anti-inflammatory activity on rat hind paw edema induced by carrageenan, with the percentage of inflammation at 1, 3, and 5 h of 35.4, 41.5, and 45.5%, respectively. The eight triterpene esters were then evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the compounds showed moderate inhibitory effects. Furthermore, compound 3c exhibited inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz [a] anthracene (DMBA) as an initiator and TPA as a promoter. The biological activities of triterpene acetate and cinnamate esters, together with the exceptionally high levels of these triterpenes in shea fat, indicate that shea nuts and shea fat (shea butter) constitute a significant source of anti-inflammatory and anti-tumor promoting compounds.

Optimization of cell-based assays to quantify the anti-inflammatory/allergic potential of test substances in 96-well format.

PubMed

Chandrasekaran, C V; Edwin Jothie, R; Kapoor, Preeti; Gupta, Anumita; Agarwal, Amit

2011-06-01

There is an insistent need for robust, reliable, and optimized assays for screening novel drugs targeting the inflammatory/allergic markers. The present study describes about the optimization of eight cell-based assays utilizing mammalian cell lines in 96-well format for quantifying anti-inflammatory/allergic drug candidates. We estimated the inhibitory response of reference compounds: 1400 W dihydrochloride on LPS-induced NO release, celecoxib on LPS-induced PGE(2) production and dexamethasone on LPS-induced pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha production by J774A.1 murine macrophages. Response of acetylsalicylic acid and celecoxib was studied on A23187-induced TXB(2) production; captopril on A23187-stimulated LTB(4) production by HL-60 cells. Effect of ketotifen fumarate was evaluated on A23187-elicited histamine release by RBL-2H3 cells. Each experiment was repeated twice to assess the reproducibility and suitability of the assays by determining appropriate statistical tools viz. %CV, S/B and Z' factor. 1400 W dihydrochloride was capable of inhibiting LPS-induced NO levels (IC(50) = 10.7 μM). Dexamethasone attenuated LPS-induced IL-1 beta (IC(50) = 70 nM), IL-6 (IC(50) = 58 nM) and TNF-alpha (IC(50) = 44 nM) release, whereas celecoxib, a specific COX-2 inhibitor showed marked reduction in LPS-induced PGE(2) (IC(50) = 23 nM) production. Captopril (IC(50) = 48 μM) and ketotifen fumarate (IC(50) = 36.4 μM) demonstrated potent inhibitory effect against A23187-stimulated LTB(4) and histamine levels, respectively. Both acetylsalicylic acid (IC(50) = 5.5 μM) and celecoxib (IC(50) = 7.9 nM) exhibited concentration-dependent decrease in TXB(2) production. Results for all the cell assays from two experiments showed a Z' factor varying from 0.30 to 0.99; the S/B ratio ranged from 2.39 to 24.92; %CV ranged between 1.52 and 20.14. The results proclaim that these cell-based assays can act as ideal tools for screening new anti-inflammatory/anti-allergic compounds.

Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways.

PubMed

Santa-Cecília, Flávia V; Socias, Benjamin; Ouidja, Mohand O; Sepulveda-Diaz, Julia E; Acuña, Leonardo; Silva, Rangel L; Michel, Patrick P; Del-Bel, Elaine; Cunha, Thiago M; Raisman-Vozari, Rita

2016-05-01

In neurodegenerative diseases, the inflammatory response is mediated by activated glial cells, mainly microglia, which are the resident immune cells of the central nervous system. Activated microglial cells release proinflammatory mediators and neurotoxic factors that are suspected to cause or exacerbate these diseases. We recently demonstrated that doxycycline protects substantia nigra dopaminergic neurons in an animal model of Parkinson's disease. This effect was associated with a reduction of microglial cell activation, which suggests that doxycycline may operate primarily as an anti-inflammatory drug. In the present study, we assessed the anti-inflammatory potential of doxycycline using lipopolysaccharide (LPS)-activated primary microglial cells in culture as a model of neuroinflammation. Doxycycline attenuated the expression of key activation markers in LPS-treated microglial cultures in a concentration-dependent manner. More specifically, doxycycline treatment lowered the expression of the microglial activation marker IBA-1 as well as the production of ROS, NO, and proinflammatory cytokines (TNF-α and IL-1β). In primary microglial cells, we also found that doxycycline inhibits LPS-induced p38 MAP kinase phosphorylation and NF-kB nuclear translocation. The present results indicate that the effect of doxycycline on LPS-induced microglial activation probably occurs via the modulation of p38 MAP kinase and NF-kB signaling pathways. These results support the idea that doxycycline may be useful in preventing or slowing the progression of PD and other neurodegenerative diseases that exhibit altered glia function.

Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice

PubMed Central

Tang, Xuchong; Wei, Ruofan; Deng, Aihua; Lei, Tingping

2017-01-01

Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke (Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight) by gavage once daily. Up to 40% alcohol (12 mL/kg body weight) was administered orally 1 h after artichoke treatment. All mice were fed for 10 consecutive days. Results showed that artichoke extract significantly prevented elevated levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, and malondialdehyde. Meanwhile, the decreased levels of superoxide dismutase and glutathione were elevated by artichoke administration. Histopathological examination showed that artichoke attenuated degeneration, inflammatory infiltration and necrosis of hepatocytes. Immunohistochemical analysis revealed that expression levels of toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB) in liver tissues were significantly suppressed by artichoke treatment. Results obtained demonstrated that artichoke extract exhibited significant preventive protective effect against acute alcohol-induced liver injury. This finding is mainly attributed to its ability to attenuate oxidative stress and suppress the TLR4/NF-κB inflammatory pathway. To the best of our knowledge, the underlying mechanisms of artichoke on acute ALD have been rarely reported. PMID:28891983

Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice.

PubMed

Tang, Xuchong; Wei, Ruofan; Deng, Aihua; Lei, Tingping

2017-09-11

Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke ( Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight) by gavage once daily. Up to 40% alcohol (12 mL/kg body weight) was administered orally 1 h after artichoke treatment. All mice were fed for 10 consecutive days. Results showed that artichoke extract significantly prevented elevated levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, and malondialdehyde. Meanwhile, the decreased levels of superoxide dismutase and glutathione were elevated by artichoke administration. Histopathological examination showed that artichoke attenuated degeneration, inflammatory infiltration and necrosis of hepatocytes. Immunohistochemical analysis revealed that expression levels of toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB) in liver tissues were significantly suppressed by artichoke treatment. Results obtained demonstrated that artichoke extract exhibited significant preventive protective effect against acute alcohol-induced liver injury. This finding is mainly attributed to its ability to attenuate oxidative stress and suppress the TLR4/NF-κB inflammatory pathway. To the best of our knowledge, the underlying mechanisms of artichoke on acute ALD have been rarely reported.

Synthesis, characterization and molecular docking studies of substituted 4-coumarinylpyrano[2,3-c]pyrazole derivatives as potent antibacterial and anti-inflammatory agents.

PubMed

Chougala, Bahubali M; Samundeeswari, S; Holiyachi, Megharaja; Shastri, Lokesh A; Dodamani, Suneel; Jalalpure, Sunil; Dixit, Sheshagiri R; Joshi, Shrinivas D; Sunagar, Vinay A

2017-01-05

A green, eco-friendly and efficient protocol has been developed and synthesized a series of coumarin based pyrano[2,3-c]pyrazole derivatives (3) by multi-component reaction (MCR). Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (4) have been isolated by the reaction of compound (3) in acidic conditions. Further, intramolecular cyclization of compounds (4) leads to C 4 C 4 chromons (9) and these compounds were screened for their biological activities using array of techniques. Most of the compounds exhibited promising antibacterial activity, in particular Gram-positive bacteria. The anti-inflammatory assay was evaluated against protein denaturation as well as HRBC membrane stabilization methods and compounds exhibit excellent anti-inflammatory activity in both methods. Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

New Butyrolactone Type Lignans from Arctii Fructus and Their Anti-inflammatory Activities.

PubMed

Yang, Ya-Nan; Huang, Xiao-Ying; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

2015-09-16

Arctiidilactone (1), a novel rare butyrolactone lignan with a 6-carboxyl-2-pyrone moiety, and 11 new butyrolactone lignans (2-12) were isolated from the fruits of Arctium lappa L., together with 5 known compounds (13-17). Their structures were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, ORD, and HRESIMS) and comparison to literature data. The absolute configurations of compounds 1-12 were determined by a combination of rotating-frame nuclear Overhauser effect spectroscopy (ROESY), circular dichroism (CD) spectroscopy, and Rh2(OCOCF3)4-induced CD spectroscopy. All of the compounds were tested for their anti-inflammatory properties in terms of suppressing the production of NO in lipopolysaccharide-induced BV2 cells. Compounds 1, 6, 8, and 10 exhibited stronger anti-inflammatory effects than the positive control curcumin, particularly 1, which exhibited 75.51, 70.72, and 61.17% inhibition at 10, 1, and 0.1 μM, respectively.

Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

PubMed

Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

2013-03-01

Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action. Georg Thieme Verlag KG Stuttgart · New York.

Antimicrobial and Anti-Inflammatory Activities of Endophytic Fungi Talaromyces wortmannii Extracts against Acne-Inducing Bacteria

PubMed Central

Schwendinger, Katja; Kreiseder, Birgit; Wiederstein, Martina; Pretsch, Dagmar; Genov, Miroslav; Hollaus, Ralph; Zinssmeister, Daniela; Debbab, Abdesamad; Hundsberger, Harald; Eger, Andreas; Proksch, Peter; Wiesner, Christoph

2014-01-01

Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8) via the NF-κB and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-α-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT) with P. acnes significantly increased NF-κB and activator protein-1 (AP-1) activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-κB and AP-1 by inhibiting IκB degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris. PMID:24887557

Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts.

PubMed

Fechtner, Sabrina; Singh, Anil; Chourasia, Mukesh; Ahmed, Salahuddin

2017-08-15

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea. Copyright © 2017. Published by Elsevier Inc.

PLA2 mediated arachidonate free radicals: PLA2 inhibition and neutralization of free radicals by anti-oxidants--a new role as anti-inflammatory molecule.

PubMed

Nanda, B L; Nataraju, A; Rajesh, R; Rangappa, K S; Shekar, M A; Vishwanath, B S

2007-01-01

PLA2 enzyme catalyses the hydrolysis of cellular phospholipids at the sn-2 position to liberate arachidonic acid and lysophospholipid to generate a family of pro-inflammatory eicosanoids and platelet activating factor. The generation of pro-inflammatory eicosanoids involves a series of free radical intermediates with simultaneous release of reactive oxygen species (superoxide and hydroxyl radicals). Reactive oxygen species formed during arachidonic acid metabolism generates lipid peroxides and the cytotoxic products such as 4-hydroxy nonenal and acrolein, which induces cellular damage. Thus PLA2 catalyzes the rate-limiting step in the production of pro-inflammatory eicosanoids and free radicals. These peroxides and reactive oxygen species in turn activates PLA2 enzyme and further attenuates the inflammatory process. Therefore scavenging these free radicals and inhibition of PLA2 enzyme simultaneously by a single molecule such as antioxidants is of great therapeutic relevance for the development of anti-inflammatory molecules. PLA2 enzymes have been classified into calcium dependent cPLA2 and sPLA2 and calcium independent iPLA2 forms. In several inflammatory diseases sPLA2 group IIA is the most abundant isoform identified. This isoform is therefore targeted for the development of anti-inflammatory molecules. Many secondary metabolites from plants and marine sponges exhibit both anti-inflammatory and antioxidant properties. Some of them include flavonoids, terpenes and alkaloids. But in terms of PLA2 inhibition and antioxidant activity, the structural aspects of flavonoids are well studied rather than terpenes and alkaloids. In this line, molecules having both anti-oxidant and PLA2 inhibitions are reviewed. A single molecule with dual activities may prove to be a powerful anti-inflammatory drug.

Klotho preservation by Rhein promotes toll-like receptor 4 proteolysis and attenuates lipopolysaccharide-induced acute kidney injury.

PubMed

Bi, Fangfang; Chen, Fang; Li, Yanning; Wei, Ai; Cao, Wangsen

2018-05-05

Renal anti-aging protein Klotho exhibits impressive properties of anti-inflammation and renal protection, however is suppressed early after renal injury, making Klotho restoration an attractive strategy of treating renal inflammatory disorders. Here, we reported that Klotho is enriched in macrophages and Klotho preservation by Rhein, an anthraquinone derived from medicinal plant rhubarb, attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation. LPS-induced pro-inflammatory NF-κB signaling and cytokine expressions coincided with Klotho repression and toll-like receptor 4 (TLR4) elevation in macrophages, renal epithelial cells, and acutely- inflamed kidney. Intriguingly, Rhein treatment effectively corrected the inverted alterations of Klotho and TLR4 and mitigated the TLR4 downstream inflammatory response in a Klotho restoration and TLR4 repression-dependent manner. Klotho inducibly associated with TLR4 after LPS stimulation and suppressed TLR4 protein abundance mainly via a proteolytic process sensitive to the inhibition of Klotho's putative β-glucuronidase activity. Consistently, Klotho knockdown by RNA interferences largely diminished the anti-inflammatory and renal protective effects of Rhein in a mouse model of acute kidney injury incurred by LPS. Thus, Klotho suppression of TLR4 via deglycosylation negatively controls TLR-associated inflammatory signaling and the endogenous Klotho preservation by Rhein or possibly other natural or synthetic compounds possesses promising potentials in the clinical treatment of renal inflammatory disorders. • Klotho is highly expressed in macrophages and repressed by LPS in vitro and in vivo. • Klotho inhibits LPS-induced TLR4 accumulation and the downstream signaling. • Klotho decreases TLR4 via a deglycosylation-associated proteolytic process. • Rhein effectively prevents acute inflammation-incurred Klotho suppression. • Rhein reversal of Klotho attenuates LPS-induced acute inflammation and kidney injury.

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

PubMed

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Design and synthesis of aloe-emodin derivatives as potent anti-tyrosinase, antibacterial and anti-inflammatory agents.

PubMed

Liu, Jinbing; Wu, Fengyan; Chen, Changhong

2015-11-15

Twenty aloe-emodin derivatives were designed, synthesized, and their biological activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, compounds with thiosemicarbazide moiety showed more potent inhibitory effects than the other compounds. The structure-activity relationships (SARs) were preliminarily discussed. The inhibition mechanism of selected compounds 1 and 13 were investigated. The results showed compound 1 was reversible inhibitor, however, compound 13 was irreversible. Kinetic analysis indicated that compound 1 was competitive tyrosinase inhibitor. Furthermore, the antibacterial activities and anti-inflammatory activities of some selected compounds were also screened. The results showed that compound 3 exhibited more potent antibacterial activity than the aloe-emodin, compounds 5 and 6 possessed more potent anti-inflammatory activities than the diacerein. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anti-inflammatory and toxicological evaluation of essential oil from Piper glabratum leaves.

PubMed

Branquinho, Lidiane Schultz; Santos, Joyce Alencar; Cardoso, Claudia Andrea Lima; Mota, Jonas da Silva; Junior, Ubirajara Lanza; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2017-02-23

Although some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited. This study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice. The acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight. In the subacute toxicity test, the females received 500 or 1000mg/kg/body weight of OEPG for 28 days. The anti-inflammatory potential of OEPG was evaluated using four models including pleurisy, edema, mechanical hyperalgesia and cold allodynia models in mouse paws. No clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD 50 is greater than 5000mg/kg. The subacute exposure to OEPG produced no significant changes in the hematological or biochemical parameters. Similarly, the histology of the organs and the estrus cycle displayed no marked alterations. OEPG exhibited anti-inflammatory activity as indicated by inhibition of the leukocyte migration (100, 300, 700mg/kg) and the protein extravasation into the pleural exudates (700mg/kg). After intraplantar injection of carrageenan, it was observed that the 700mg/kg dose of OEPG reduced edema formation and decreased the sensitivity to mechanical stimulation and cold. These results demonstrate the anti-inflammatory potential of the essential oil of P. glabratum leaves in the absence of toxicity in female mice. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effect of anthocyanins via modulation of nuclear factor-κB and mitogen-activated protein kinase signaling cascades.

PubMed

Vendrame, Stefano; Klimis-Zacas, Dorothy

2015-06-01

Anthocyanins are a group of bioactive compounds present in plant foods. Although they have consistently shown an anti-inflammatory effect both in vitro and in vivo, their mechanisms of action are not fully understood and have only recently begun to be elucidated. The aim of this review is to highlight the anti-inflammatory activity of anthocyanins, including their effect on the expression of several genes involved in inflammation. The available evidence suggests that their anti-inflammatory action can be attributed primarily to their antioxidant properties, which result in downregulation of the redox-sensitive nuclear factor-κB signaling pathway. Other pathways at least partly involved in the inflammatory response, particularly the mitogen-activated protein kinase pathways, also appear to play a role. A discussion is presented on the most effective dose of anthocyanins, the differential contribution of specific compounds, the comparative effects of anthocyanins versus other anti-inflammatory phenolic compounds, and the extent to which the observed biological activities are exerted by anthocyanins themselves or their metabolites. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

PubMed

Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F

2008-10-01

Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.

Design, synthesis and investigation of potential anti-inflammatory activity of O-alkyl and O-benzyl hesperetin derivatives.

PubMed

Huang, Ai-Ling; Zhang, Yi-Long; Ding, Hai-Wen; Li, Bo; Huang, Cheng; Meng, Xiao-Ming; Li, Jun

2018-05-28

Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl 4 -induced acute liver injury mouse models. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride.

PubMed

Sondhi, Sham M; Dinodia, Monica; Jain, Shubhi; Kumar, Ashok

2008-12-01

A series of substituted N-methylisonicotinamidine (2a-f), N-methylpyrazine-2-carboxamidine (2g-i) derivatives were synthesized by reaction of amidine derivatives (1a-i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a-i) were obtained by the reaction of amidine derivatives (1a-i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a-i and 3a-i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, (1)H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.

Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding and inhibition of NFκB transactivation

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

Park, Mi Hee; Kang, Dong Woo; Jung, Yunjin

2013-12-06

Highlights: •We found CAFÉ, a natural product that suppresses expression and activity of PLD1. •CAPE decreased PLD1 expression by inhibiting NFκB transactivation. •CAPE rapidly inhibited PLD activity via its binding to a Cys837 of PLD1. •PLD1 downregulation by CAPE inhibited invasion and proliferation of glioma cells. -- Abstract: Upregulation of phospholipase D (PLD) is functionally linked with oncogenic signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active compound of propolis extract that exhibits anti-proliferative, anti-inflammatory, anti-oxidant, and antineoplastic properties. In this study, we demonstrated that CAPE suppressed the expression of PLD1 at the transcriptional level via inhibition ofmore » binding of NFκB to PLD1 promoter. Moreover, CAPE, but not its analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced downregulation of PLD1 suppressed invasion and proliferation of glioma cells. Taken together, the results of this study indicate that CAPE might contribute to anti-neoplastic effect by targeting PLD1.« less

Targeting the Hemoglobin Scavenger receptor CD163 in Macrophages Highly Increases the Anti-inflammatory Potency of Dexamethasone

PubMed Central

Graversen, Jonas H; Svendsen, Pia; Dagnæs-Hansen, Frederik; Dal, Jakob; Anton, Gabriele; Etzerodt, Anders; Petersen, Mikkel D; Christensen, Peter A; Møller, Holger J; Moestrup, Søren K

2012-01-01

Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side effects such as bone mobilization, muscle mass loss, immunosuppression, and metabolic alterations make glucocorticoid therapy a difficult balance. The therapeutic anti-inflammatory effect of glucocorticoids relies largely on the suppressed release of tumor-necrosis factor-α and other cytokines by macrophages at the sites of inflammation. We have now developed a new biodegradable anti-CD163 antibody-drug conjugate that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages. The conjugate, that in average contains four dexamethasone molecules per antibody, exhibits retained high functional affinity for CD163. In vitro studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti-inflammatory effect of the conjugate measured as reduced lipopolysaccharide-induced secretion of tumor-necrosis factor-α. The in vivo potency of conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone. In contrast to a strong systemic effect of nonconjugated dexamethasone, the equipotent dose of the conjugate had no such effect, measured as thymus lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol levels. In conclusion, the study shows antibody-drug conjugates as a future approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug delivery. PMID:22643864

Bone marrow mesenchymal stem cells ameliorate lung injury through anti-inflammatory and antibacterial effect in COPD mice.

PubMed

Liu, Hong-Mei; Liu, Yi-Tong; Zhang, Jing; Ma, Li-Jun

2017-08-01

The anti-inflammatory and antibacterial mechanisms of bone marrow mesenchymal stem cells (MSCs) ameliorating lung injury in chronic obstructive pulmonary disease (COPD) mice induced by cigarette smoke and Haemophilus Parainfluenza (HPi) were studied. The experiment was divided into four groups in vivo: control group, COPD group, COPD+HPi group, and COPD+HPi+MSCs group. The indexes of emphysematous changes, inflammatory reaction and lung injury score, and antibacterial effects were evaluated in all groups. As compared with control group, emphysematous changes were significantly aggravated in COPD group, COPD+HPi group and COPD+HPi+MSCs group (P<0.01), the expression of necrosis factor-kappaB (NF-κB) signal pathway and proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) were increased (P<0.01), and the phagocytic activity of alveolar macrophages was downregulated (P<0.01). As compared with COPD group, lung injury score, inflammatory cells and proinflammatory cytokines were significantly increased in the BALF of COPD+HPi group and COPD+HPi+MSCs group (P<0.01). As compared with COPD+HPi group, the expression of tumor necrosis factor-α stimulated protein/gene 6 (TSG-6) was increased, the NF-κB signal pathway was depressed, proinflammatory cytokine was significantly reduced, the anti-inflammatory cytokine IL-10 was increased, and lung injury score was significantly reduced in COPD+HPi+MSCs group. Meanwhile, the phagocytic activity of alveolar macrophages was significantly enhanced and bacterial counts in the lung were decreased. The results indicated cigarette smoke caused emphysematous changes in mice and the phagocytic activity of alveolar macrophages was decreased. The lung injury of acute exacerbation of COPD mice induced by cigarette smoke and HPi was alleviated through MSCs transplantation, which may be attributed to the fact that MSCs could promote macrophages into anti-inflammatory phenotype through secreting TSG-6, inhibit NF-кB signaling pathway, and reduce inflammatory response through reducing proinflammatory cytokines and promoting the expression of the anti-inflammatory cytokine. Simultaneously, MSCs could enhance phagocytic activity of macrophages and bacterial clearance. Meanwhile, we detected anti-inflammatory and antibacterial activity of macrophages regulated by MSCs in vitro. As compared with RAW264.7+HPi+CSE group, the expression of NF-кB p65, IL-1β, IL-6 and TNF-α was significantly reduced, and the phagocytic activity of macrophages was significantly increased in RAW264.7+HPi+CSE+MSCs group (P<0.01). The result indicated the macrophages co-cultured with MSCs may inhibit NF-кB signaling pathway and promote phagocytosis by paracrine mechanism.

SIRT1/Adenosine Monophosphate-Activated Protein Kinase α Signaling Enhances Macrophage Polarization to an Anti-inflammatory Phenotype in Rheumatoid Arthritis

PubMed Central

Park, So Youn; Lee, Sung Won; Lee, Sang Yeob; Hong, Ki Whan; Bae, Sun Sik; Kim, Koanhoi; Kim, Chi Dae

2017-01-01

Macrophages are crucially involved in the pathogenesis of rheumatoid arthritis (RA). Macrophages of the M1 phenotype act as pro-inflammatory mediators in synovium, whereas those of the M2 phenotype suppress inflammation and promote tissue repair. SIRT1 is a class 3 histone deacetylase with anti-inflammatory characteristics. However, the role played by SIRT1 in macrophage polarization has not been defined in RA. We investigated whether SIRT1 exerts anti-inflammatory effects by modulating M1/M2 polarization in macrophages from RA patients. In this study, SIRT1 activation promoted the phosphorylation of an adenosine monophosphate-activated protein kinase (AMPK) α/acetyl-CoA carboxylase in macrophages exposed to interleukin (IL)-4, and that this resulted in the expressions of M2 genes, including MDC, FcεRII, MrC1, and IL-10, at high levels. Furthermore, these expressions were inhibited by sirtinol (an inhibitor of SIRT1) and compound C (an inhibitor of AMPK). Moreover, SIRT1 activation downregulated LPS/interferon γ-mediated NF-κB activity by inhibiting p65 acetylation and the expression of M1 genes, such as CCL2, iNOS, IL-12 p35, and IL-12 p40. Macrophages from SIRT1 transgenic (Tg)-mice exhibited enhanced polarization of M2 phenotype macrophages and reduced polarization of M1 phenotype macrophages. In line with these observations, SIRT1-Tg mice showed less histological signs of arthritis, that is, lower TNFα and IL-1β expressions and less severe arthritis in the knee joints, compared to wild-type mice. Taken together, the study shows activation of SIRT1/AMPKα signaling exerts anti-inflammatory activities by regulating M1/M2 polarization, and thereby reduces inflammatory responses in RA. Furthermore, it suggests that SIRT1 signaling be viewed as a therapeutic target in RA. PMID:28966618

Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells.

PubMed

Huang, Wen-Chung; Wu, Shu-Ju; Tu, Rong-Syuan; Lai, You-Rong; Liou, Chian-Jiun

2015-06-01

Phloretin, a flavonoid isolated from the apple tree, is reported to have anti-inflammatory, anti-oxidant, and anti-adiposity effects. In this study, we evaluated the suppressive effects of phloretin on intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase (COX)-2 expression in IL-1β-stimulated human lung epithelial A549 cells. The cells were pretreated with various concentrations of phloretin (3-100 μM), followed by induced inflammation by IL-1β. Phloretin inhibited levels of prostaglandin E2, decreased COX-2 expression, and suppressed IL-8, monocyte chemotactic protein 1, and IL-6 production. It also decreased ICAM-1 gene and protein expression and suppressed monocyte adhesion to inflammatory A549 cells. Phloretin also significantly inhibited Akt and mitogen-activated protein kinase (MAPK) phosphorylation and decreased nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. In addition, ICAM-1 and COX-2 expression was suppressed by pretreatment with both MAPK inhibitors and phloretin in inflammatory A549 cells. However, phlorizin, a derivative of phloretin, did not suppress the inflammatory response in IL-1β-stimulated A549 cells. These results suggest that phloretin might have an anti-inflammatory effect by inhibiting proinflammatory cytokine, COX-2, and ICAM-1 expression via blocked NF-κB and MAPK signaling pathways.

Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum.

PubMed

BenSaad, Lamees A; Kim, Kah Hwi; Quah, Chin Chew; Kim, Wee Ric; Shahimi, Mustafa

2017-01-14

Punica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells. The compounds ellagic acid, gallic acid and punicalagin A&B were isolated from EtOAc by high performance liquid chromatography (HPLC) and further identified by mass spectrometry (MS). The inhibitory effect of ellagic acid, gallic acid and punicalagin A&B were evaluated on the production of LPS-induced NO by Griess reagent, PGE-2 and IL-6 by immunoassay kit and prostaglandin E2 competitive ELISA kit, and COX-2 by Western blotting. Ellagic acid, gallic acid and punicalagin A&B potentially inhibited LPS-induced NO, PGE-2 and IL-6 production. The results indicate that ellagic acid, gallic acid and punicalagin may be the compounds responsible for the anti-inflammatory potential of P. granatum.

Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

PubMed

Balakumar, C; Lamba, P; Kishore, D Pran; Narayana, B Lakshmi; Rao, K Venkat; Rajwinder, K; Rao, A Raghuram; Shireesha, B; Narsaiah, B

2010-11-01

A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies. Crown Copyright © 2010. Published by Elsevier Masson SAS. All rights reserved.

Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps on carrageenan-induced inflammation in mice.

PubMed

Min, Sung-Won; Kim, Nam-Jae; Baek, Nam-In; Kim, Dong-Hyun

2009-09-25

Artemisia princeps Pampanini (family Asteraceae) is an herbal medicine widely used as a hepatoprotective, antioxidative, anti-inflammatory, and antibacterial agent in Korea, China, and Japan. This study aimed to elucidate the anti-inflammatory effect of the main constituents, eupatilin and jaceosidin, isolated from Artemisia princeps. We used carrageenan-induced inflammation in an air pouch on the back of mice and carrageenan-induced hind paw edema in rats to determine the anti-inflammatory effects of eupatilin and jaceosidin. Inflammatory makers, such as expression of pro-inflammatory cytokines and cyclooxygenase (COX)-2, and activation of nuclear factor-kappa B (NF-kappaB), were measured by enzyme-linked immunosorbent assays and immunoblot analyses. Eupatilin and jaceosidin blocked carrageenan-induced increase in leukocyte number and protein levels in air pouch exudates. Eupatilin and jaceosidin inhibited COX-2 expression and NF-kappaB activation, and markedly reduced TNF-alpha, IL-1beta, and prostaglandin E2 (PGE(2)) levels. They also inhibited hind paw edema induced by carrageenan. Eupatilin and jaceosidin had similar activity. These findings suggest that eupatilin and jaceosidin may reduce inflammation by inhibiting NF-kappaB activation, and that Artemisia princeps inhibits inflammation because of these constituents.

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-Helicobacter pylori activity of anacardic acids from Amphipterygium adstringens.

PubMed

Castillo-Juárez, Israel; Rivero-Cruz, Fausto; Celis, Heliodoro; Romero, Irma

2007-10-08

Amphipterygium adstringens (Schltdl.) Standl. (Anacardiaceae) is widely used in traditional Mexican medicine for the treatment of gastritis and ulcers. In this work, we studied the anti-Helicobacter pylori activity of its bark, this Gram-negative bacterium is considered the major etiological agent of chronic active gastritis and peptic ulcer disease, and it is linked to gastric carcinoma. From a bio-guided assay of the fractions obtained form a continuous Soxhlet extraction of the bark, we identified that petroleum ether fraction had significant antimicrobial activity against Helicobacter pylori. From this fraction, we isolated an anacardic acids mixture and three known triterpenes: masticadienonic acid; 3alpha-hydroxymasticadienonic acid; 3-epi-oleanolic; as well as the sterol beta-sitosterol. Only the anacardic acids mixture exhibits a potent dose-dependent antibacterial activity (MIC=10 microg/ml in broth cultures). It is enriched in saturated alkyl phenolic acids (C15:0, C16:0, C17:0 C19:0) which represents a novel source of these compounds with potent anti-Helicobacter pylori activity. The promising use of anacardic acids and Amphipterygium adstringens bark in the development of an integral treatment of Helicobacter pylori diseases is discussed.

Design and environmentally benign synthesis of novel thiophene appended pyrazole analogues as anti-inflammatory and radical scavenging agents: Crystallographic, in silico modeling, docking and SAR characterization.

PubMed

Prabhudeva, Malledevarapura Gurumurthy; Bharath, Srinivasan; Kumar, Achutha Dileep; Naveen, Shivalingegowda; Lokanath, Neratur Krishnappagowda; Mylarappa, Bantaganahalli Ningappa; Kumar, Kariyappa Ajay

2017-08-01

Oxidative-stress induces inflammatory diseases and infections caused by drug-resistant microbial strains are on the rise necessitating the discovery of novel small-molecules for intervention therapy. The current study presents an effective and new green protocol for the synthesis of thiophene-appended pyrazoles through 3+2 annulations method. Chalcones 3(a-g) were prepared from 5-chloro-2-acetylthiophene and aromatic aldehydes by Claisen-Schmidt approach. The reaction of chalcones 3(a-g) with phenylhydrazine hydrochlorides 4(a-b) in acetic acid (30%) medium and also with freshly prepared citrus extract medium under reflux conditions produced the thiophene appended pyrazoles 5(a-l) in moderate yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, elemental analysis and single crystal X-ray diffraction studies. Further, preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5d, 5e and 5l have excellent anti-inflammatory activities. Further, compounds 5c, 5d, 5g, and 5i exhibited excellent DPPH radical scavenging abilities in comparison with the standard ascorbic acid. Furthermore, using detailed structural modeling and docking efforts, combined with preliminary SAR, we show possible structural and chemical features on both the small-molecules and the protein that might contribute to the binding and inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

Green synthesis of gold nanoparticles using chlorogenic acid and their enhanced performance for inflammation.

PubMed

Hwang, Su Jung; Jun, Sang Hui; Park, Yohan; Cha, Song-Hyun; Yoon, Minho; Cho, Seonho; Lee, Hyo-Jong; Park, Youmie

2015-10-01

Here we developed a novel green synthesis method for gold nanoparticles (CGA-AuNPs) using chlorogenic acid (CGA) as reductants without the use of other chemicals and validated the anti-inflammatory efficacy of CGA-AuNPs in vitro and in vivo. The resulting CGA-AuNPs appeared predominantly spherical in shape with an average diameter of 22.25±4.78nm. The crystalline nature of the CGA-AuNPs was confirmed by high-resolution X-ray diffraction and by selected-area electron diffraction analyses. High-resolution liquid chromatography/electrospray ionization mass spectrometry revealed that the caffeic acid moiety of CGA forms quinone structure through a two-electron oxidation causing the reduction of Au(3+) to Au(0). When compared to CGA, CGA-AuNPs exhibited enhanced anti-inflammatory effects on NF-κB-mediated inflammatory network, as well as cell adhesion. Collectively, green synthesis of CGA-AuNPs using bioactive reductants and mechanistic studies based on mass spectrometry may open up new directions in nanomedicine and CGA-AuNPs can be an anti-inflammatory nanomedicine for future applications. Gold nanoparticles (Au NPs) have been shown to be very useful in many applications due to their easy functionalization capability. In this article, the authors demonstrated a novel method for the synthesis of gold nanoparticles using chlorogenic acid (CGA) as reductants. In-vitro experiments also confirmed biological activity of the resultant gold nanoparticles. Further in-vivo studies are awaited. Copyright © 2015 Elsevier Inc. All rights reserved.

Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE-/- mouse model of atherosclerosis with alterations in IL10/AMPKα pathway.

PubMed

Thompson, D; Morrice, N; Grant, L; Le Sommer, S; Ziegler, K; Whitfield, P; Mody, N; Wilson, H M; Delibegović, M

2017-08-01

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD. We generated novel macrophage-specific PTP1B knockout mice on atherogenic background (ApoE -/- /LysM-PTP1B). Mice were fed standard or pro-atherogenic diet, and body weight, adiposity (echoMRI), glucose homeostasis, atherosclerotic plaque development, and molecular, biochemical and targeted lipidomic eicosanoid analyses were performed. Myeloid-PTP1B knockout mice on atherogenic background (ApoE -/- /LysM-PTP1B) exhibited a striking improvement in glucose homeostasis, decreased circulating lipids and decreased atherosclerotic plaque lesions, in the absence of body weight/adiposity differences. This was associated with enhanced phosphorylation of aortic Akt, AMPKα and increased secretion of circulating anti-inflammatory cytokine interleukin-10 (IL-10) and prostaglandin E2 (PGE 2 ), without measurable alterations in IR phosphorylation, suggesting a direct beneficial effect of myeloid-PTP1B targeting. Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE -/- mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk.

Flavonoid fraction of Bergamot juice reduces LPS-induced inflammatory response through SIRT1-mediated NF-κB inhibition in THP-1 monocytes.

PubMed

Risitano, Roberto; Currò, Monica; Cirmi, Santa; Ferlazzo, Nadia; Campiglia, Pietro; Caccamo, Daniela; Ientile, Riccardo; Navarra, Michele

2014-01-01

Plant polyphenols exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory genes. Recently, Citrus bergamia has been studied as a natural source of bioactive molecules with antioxidant activity, but few studies have focused on molecular mechanisms underlying their potential beneficial effects. Several findings have suggested that polyphenols could influence cellular function by acting as activators of SIRT1, a nuclear histone deacetylase, involved in the inhibition of NF-κB signaling. On the basis of these observations we studied the anti-inflammatory effects produced by the flavonoid fraction of the bergamot juice (BJe) in a model of LPS-stimulated THP-1 cell line, focusing on SIRT1-mediated NF-κB inhibition. We demonstrated that BJe inhibited both gene expression and secretion of LPS-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by a mechanism involving the inhibition of NF-κB activation. In addition, we showed that BJe treatment reversed the LPS-enhanced acetylation of p65 in THP-1 cells. Interestingly, increasing concentrations of Sirtinol were able to suppress the inhibitory effect of BJe via p65 acetylation, underscoring that NF-κB-mediated inflammatory cytokine production may be directly linked to SIRT1 activity. These results suggest that BJe may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process.

Antioxidant activity and peroxidase inhibition of Amazonian plants extracts traditionally used as anti-inflammatory.

PubMed

de Vargas, Fabiano S; Almeida, Patricia D O; de Boleti, Ana Paula A; Pereira, Maria M; de Souza, Tatiane P; de Vasconcellos, Marne C; Nunez, Cecilia Veronica; Pohlit, Adrian M; Lima, Emerson S

2016-02-27

The Amazon is the largest rainforest in the world and is home to a rich biodiversity of medicinal plants. Several of these plants are used by the local population for the treatment of diseases, many of those with probable anti-inflammatory effect. The aim of the present investigation was to evaluate the in vitro antioxidant and anti-peroxidases potential of the ethanol extracts of five plants from the Brazilian Amazon (Byrsonima japurensis, Calycophyllum spruceanum, Maytenus guyanensis, Passiflora nitida and Ptychopetalum olacoides). DPPH, ABTS, superoxide anion radical, singlet oxygen and the β-carotene bleaching methods were employed for characterization of free radical scavenging activity. Also, total polyphenols were determined. Antioxidant activities were evaluated using murine fibroblast NIH3T3 cell. Inhibition of HRP and MPO were evaluated using amplex red® as susbtract. The stem bark extracts of C. spruceanum and M. guyanensis provided the highest free radical scavenging activities. C. spruceanum exhibited IC50 = 7.5 ± 0.9, 5.0 ± 0.1, 18.2 ± 3.0 and 92.4 ± 24.8 μg/mL for DPPH(•), ABTS(+•), O2 (-•) and (1)O2 assays, respectively. P. olacoides and C. spruceanum extracts also inhibited free radicals formation in the cell-based assay. At a concentration of 100 μg/mL, the extracts of C. spruceanum, B. japurensis inhibited horseradish peroxidase by 62 and 50 %, respectively. C. spruceanum, M. guyanensis, B. japurensis also inhibited myeloperoxidase in 72, 67 and 56 %, respectively. This work supports the folk use these species that inhibited peroxidases and exhibited significant free radical scavenging and antioxidant activities what can be related to treatment of inflammation.

Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-κB Pathway in HBE16 Airway Epithelial Cells.

PubMed

Dong, Shou-jin; Zhong, Yun-qing; Lu, Wen-ting; Li, Guan-hong; Jiang, Hong-li; Mao, Bing

2015-08-01

Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 μg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 μg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/β and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in clinical practice.

Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities.

PubMed

Thitimuta, Surached; Pithayanukul, Pimolpan; Nithitanakool, Saruth; Bavovada, Rapepol; Leanpolchareanchai, Jiraporn; Saparpakorn, Patchreenart

2017-03-04

The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) ( Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl₄-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA) oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE's principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl₄-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl₄ intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.

Protective effects of melatonin on lipopolysaccharide-induced mastitis in mice.

PubMed

Shao, Guoxi; Tian, Yinggang; Wang, Haiyu; Liu, Fangning; Xie, Guanghong

2015-12-01

Melatonin, a secretory product of the pineal gland, has been reported to have antioxidant and anti-inflammatory effects. However, the protective effects of melatonin on lipopolysaccharide (LPS)-induced mastitis have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of melatonin on LPS-induced mastitis both in vivo and in vitro. In vivo, our results showed that melatonin attenuated LPS-induced mammary histopathologic changes and myeloperoxidase (MPO) activity. Melatonin also inhibited LPS-induced inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in mammary tissues. In vitro, melatonin was found to inhibit LPS-induced TNF-α and IL-6 production in mouse mammary epithelial cells. Melatonin also suppressed LPS-induced Toll-like receptor 4 (TLR4) expression and nuclear factor-kappaB (NF-κB) activation in a dose-dependent manner. In addition, melatonin was found to up-regulate the expression of PPAR-γ. Inhibition of PPAR-γ by GW9662 reduced the anti-inflammatory effects of melatonin. In conclusion, we found that melatonin, for the first time, had protective effects on LPS-induced mastitis in mice. The anti-inflammatory mechanism of melatonin was through activating PPAR-γ which subsequently inhibited LPS-induced inflammatory responses. Copyright © 2015 Elsevier B.V. All rights reserved.

New insights into the ameliorative effects of ferulic acid in pathophysiological conditions.

PubMed

Ghosh, Sumit; Basak, Priyanka; Dutta, Sayanta; Chowdhury, Sayantani; Sil, Parames C

2017-05-01

Ferulic acid, a natural phytochemical has gained importance as a potential therapeutic agent by virtue of its easy commercial availability, low cost and minimal side-effects. It is a derivative of curcumin and possesses the necessary pharmacokinetic properties to be retained in the general circulation for several hours. The therapeutic effects of ferulic acid are mediated through its antioxidant and anti-inflammatory properties. It exhibits different biological activities such as anti-inflammatory, anti-apoptotic, anti-carcinogenic, anti-diabetic, hepatoprotective, cardioprotective, neuroprotective actions, etc. The current review addresses its therapeutic effects under different pathophysiological conditions (eg. cancer, cardiomyopathy, skin disorders, brain disorders, viral infections, diabetes etc.). Copyright © 2017 Elsevier Ltd. All rights reserved.

Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.

PubMed

Huang, Wen-Chung; Dai, Yi-Wen; Peng, Hui-Ling; Kang, Chiao-Wei; Kuo, Chun-Yu; Liou, Chian-Jiun

2015-07-01

Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-inflammatory activity of traditional Chinese medicinal herbs.

PubMed

Pan, Min-Hsiung; Chiou, Yi-Shiou; Tsai, Mei-Ling; Ho, Chi-Tang

2011-10-01

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for various human diseases. Thus, suppressing chronic inflammation has the potential to delay, prevent, and control various chronic diseases, including cerebrovascular, cardiovascular, joint, skin, pulmonary, blood, lymph, liver, pancreatic, and intestinal diseases. Various natural products from traditional Chinese medicine (TCM) have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. In vivo and/or in vitro studies have demonstrated that anti-inflammatory effects of TCM occur by inhibition of the expression of master transcription factors (for example, nuclear factor-κB (NF-κB)), pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), chemokines (for example, chemokine (C-C motif) ligand (CCL)-24), intercellular adhesion molecule expression and pro-inflammatory mediators (for example, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)). However, a handful of review articles have focused on the anti-inflammatory activities of TCM and explore their possible mechanisms of action. In this review, we summarize recent research attempting to identify the anti-inflammatory constituents of TCM and their molecular targets that may create new opportunities for innovation in modern pharmacology.

East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease.

PubMed

Sharma, Manju; Levenson, Corey; Browning, John C; Becker, Emily M; Clements, Ian; Castella, Paul; Cox, Michael E

2018-01-01

Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro . In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders.

East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease

PubMed Central

Sharma, Manju; Levenson, Corey; Browning, John C.; Becker, Emily M.; Clements, Ian; Castella, Paul; Cox, Michael E.

2018-01-01

Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders. PMID:29593534

In Vitro Anti-inflammatory Effects of the Phenylbutyric Acid Metabolite Phenylacetyl Glutamine.

PubMed

Hazekawa, Mai; Ono, Kazuhiko; Nishinakagawa, Takuya; Kawakubo-Yasukochi, Tomoyo; Nakashima, Manabu

2018-06-01

Sodium 4-phenylbutyrate (PBA), which exerts a wide range of anti-inflammatory effects, is rapidly cleared from the body (approximately 98%) by urinary excretion by 24 h after oral treatment in humans. PBA was almost entirely excreted to urine as phenylacetyl glutamine (PAGln). However, no data describe the potential anti-inflammatory effects of PAGln. The purpose of this study was to evaluate the anti-inflammatory effects of PAGln on mouse spleen cells and peritoneal cavity cells, and explore the potential mechanism underlying this effect. PAGln was added to mouse spleen cell cultures stimulated by concanavalin A, or mouse peritoneal cavity cell cultures stimulated by lipopolysaccharide. After 72 h of culture, levels of inflammatory cytokines in culture supernatants were measured using a sandwich enzyme-linked immunosorbent assay system, and levels of inflammatory proteins were assessed by Western blotting. PAGln significantly inhibited inflammatory cytokine (interferon-γ, interleukin-6, and tumor necrosis factor-α) production, decrease of cell number in the spleen cell, and suppressed the expression of inflammatory proteins (nuclear factor κB, and inducible nitric oxide synthase). These results suggest that PAGln possesses anti-inflammatory activity via inhibition of T cell activation and Toll-like receptor 4 signaling. This study of the anti-inflammatory mechanism of PAGln provides useful information about its potential for therapeutic applications.

Anti-inflammatory effect of sophoraflavanone G isolated from Sophora flavescens in lipopolysaccharide-stimulated mouse macrophages.

PubMed

Wun, Zih-Yi; Lin, Chwan-Fwu; Huang, Wen-Chung; Huang, Yu-Ling; Xu, Pei-Yin; Chang, Wei-Tien; Wu, Shu-Ju; Liou, Chian-Jiun

2013-12-01

Sophoraflavanone G (SG; 5,7,D, 2',4'-tetrahydroxy-8-lavandulylflavanone) has been isolated from Sophora flavescens and found to be effective against bacteria and to decrease cyclooxygenase (COX)-2 expression in RAW 264.7 macrophage. However, the anti-inflammatory mechanisms of SG are not well understood. RAW 264.7 cells were pretreated with various concentrations of SG (2.5-20 μM) and inflammatory responses were induced with lipopolysaccharide. Using enzyme-linked immunosorbent assay, the levels of pro-inflammatory cytokines and prostaglandin E2 (PGE2) were determined. Western blot was used to examine the protein expression of inducible nitric oxide synthase (iNOS), COX-2, and heme oxygenase-1 (HO-1). To investigate the molecular mechanism, we analyzed inflammatory-associated signaling pathways, including nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK). SG inhibited the levels of nitric oxide and PGE2 and decreased the production of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α. The expression of iNOS and COX-2 was also suppressed. However, SG increased HO-1 production in a concentration-dependent manner and significantly decreased MAPK activation and inhibited NF-κB subunit p65 proteins to translocate into the nucleus. These results suggest that SG has an anti-inflammatory effect, inhibiting pro-inflammatory cytokines and mediators production via interruption of the NF-κB and MAPK signaling pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

PubMed

Maitra, Rangan; Porter, Melissa A; Huang, Shan; Gilmour, Brian P

2009-05-13

Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL-8 measurements and high-content fluorescent imaging of NFkappaB subunit p65 translocation. Since the airways of CF patients can be specifically targeted for delivery of therapeutics, we propose that WFA should be further studied as an anti-inflammatory agent in models of CF related inflammation mediated by NFkappaB.

Hesperetin derivative-14 alleviates inflammation by activating PPAR-γ in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells.

PubMed

Chen, Xin; Ding, Hai-Wen; Li, Hai-Di; Huang, Hui-Min; Li, Xiao-Feng; Yang, Yang; Zhang, Yi-Long; Pan, Xue-Yin; Huang, Cheng; Meng, Xiao-Ming; Li, Jun

2017-05-15

Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl 4 -induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-γ in vivo and in vitro. Interestingly, over-expression of PPAR-γ had anti-inflammatory effects on the expressions of TNF-α, IL-6, and IL-1β, whereas, knockdown of PPAR-γ with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-γ expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-γ. Together, these results suggested that HD-14 served as an activator of PPAR-γ and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory activity of standardized dichloromethane extract of Salvia connivens on macrophages stimulated by LPS.

PubMed

González-Chávez, Marco Martín; Ramos-Velázquez, Cinthia Saraí; Serrano-Vega, Roberto; Pérez-González, Cuauhtemoc; Sánchez-Mendoza, Ernesto; Pérez-Gutiérrez, Salud

2017-12-01

A previous study demonstrated that the chloroform extract of Salvia connivens Epling (Lamiaceae) has anti-inflammatory activity. Identification of the active components in the dicholorometane extract (DESC), and, standardization of the extract based in ursolic acid. DESC was prepared by percolation with dichlromethane and after washed with hot hexane, its composition was determined by CG-MS and NMR, and standardized by HPLC. The anti-inflammatory activity was tested on acute TPA-induced mouse ear oedema at doses of 2.0 mg/ear. The cell viability of macrophages was evaluated by MTT method, and pro- and anti-inflammatory interleukin levels were measured using an ELISA kit. Ursolic acid, oleanolic acid, dihydroursolic acid and eupatorin were identified in DESC, which was standardized based on the ursolic acid concentration (126 mg/g). The anti-inflammatory activities of DESC, the acid mixture, and eupatorin (2 mg/ear) were 60.55, 57.20 and 56.40% inhibition, respectively, on TPA-induced ear oedema. The IC 50 of DESC on macrophages was 149.4 μg/mL. DESC (25 μg/mL) significantly reduced TNF-α (2.0-fold), IL-1β (2.2-fold) and IL-6 (2.0-fold) in macrophages stimulated with LPS and increased the production of IL-10 (1.9-fold). Inflammation is a basic response to injuries, and macrophages are involved in triggering inflammation. Macrophage cells exhibit a response to LPS, inducing inflammatory mediators, and DESC inhibits the biosynthesis of the pro-inflammatory and promote anti-inflammatory cytokines. DESC has an anti-inflammatory effect; reduced the levels of IL-1β, Il-6 and TNF-α; and increases IL-10 in macrophages stimulated with LPS. Ursolic acid is a good phytochemical marker.

Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction.

PubMed

Scholtysek, Carina; Krukiewicz, Aleksandra A; Alonso, José-Luis; Sharma, Karan P; Sharma, Pal C; Goldmann, Wolfgang H

2009-02-13

Saw Palmetto Berry Extract (SPBE) is applied for prostate health and treatment of urinary tract infections, nonbacterial prostitis and Benign Prostatic Hyperplasia (BPH) in man. An assumption is that SPBE affects tumor cell progression and migration in breast and prostate tissue. In this work, DU-145 cells were used to demonstrate that SPBE and its sterol components, beta-sitosterol and stigmasterol, inhibit prostate cancer growth by increasing p53 protein expression and also inhibit carcinoma development by decreasing p21 and p27 protein expression. In the presence of cholesterol, these features are not only reversed but increased significantly. The results show for the first time the potential of SPBE, beta-sitosterol and stigmasterol as potential anti-tumor agents. Since the protein p53 is also regarded as nuclear matrix protein facilitating actin cytoskeletal binding, 2D tractions were measured. The cell adhesion strength in the presence of SPBE, beta-sitosterol and cholesterol and the observation was that the increase in p53 expression triggered an increase in the intracellular force generation. The results suggest a dual function of p53 in cells.

Penicillinolide A: a new anti-inflammatory metabolite from the marine fungus Penicillium sp. SF-5292.

PubMed

Lee, Dong-Sung; Ko, Wonmin; Quang, Tran Hong; Kim, Kyoung-Su; Sohn, Jae Hak; Jang, Jae-Hyuk; Ahn, Jong Seog; Kim, Youn-Chul; Oh, Hyuncheol

2013-11-12

In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher's method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation.

Penicillinolide A: A New Anti-Inflammatory Metabolite from the Marine Fungus Penicillium sp. SF-5292

PubMed Central

Lee, Dong-Sung; Ko, Wonmin; Quang, Tran Hong; Kim, Kyoung-Su; Sohn, Jae Hak; Jang, Jae-Hyuk; Ahn, Jong Seog; Kim, Youn-Chul; Oh, Hyuncheol

2013-01-01

In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher’s method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation. PMID:24225730

Anticancer and anti-inflammatory activities of some dietary cucurbits.

PubMed

Sharma, Dhara; Rawat, Indu; Goel, H C

2015-04-01

In this study, we investigated few dietary cucurbits for anticancer activity by monitoring cytotoxic (MTT and LDH assays), apoptotic (caspase-3 and annexin-V assays), and also their anti-inflammatory effects by IL-8 cytokine assay. Aqua-alcoholic (50:50) whole extracts of cucurbits [Lagenaria siceraria (Ls), Luffa cylindrica (Lc) and Cucurbita pepo (Cp)] were evaluated in colon cancer cells (HT-29 and HCT-15) and were compared with isolated biomolecule, cucurbitacin-B (Cbit-B). MTT and LDH assays revealed that the cucurbit extracts and Cbit-B, in a concentration dependent manner, decreased the viability of HT-29 and HCT-15 cells substantially. The viability of lymphocytes was, however, only marginally decreased, yielding a potential advantage over the tumor cells. Caspase-3 assay revealed maximum apoptosis with Ls while annexin V assay demonstrated maximum efficacy of Lc in this context. These cucurbits have also shown decreased secretion of IL-8, thereby revealing their anti-inflammatory capability. The results have demonstrated the therapeutic potential of dietary cucurbits in inhibiting cancer and inflammatory cytokine.

Complement activation and interleukin response in major abdominal surgery.

PubMed

Kvarnström, A L; Sarbinowski, R T; Bengtson, J-P; Jacobsson, L M; Bengtsson, A L

2012-05-01

The objective of this study was to evaluate whether major abdominal surgery leads to complement activation and interleukin response and whether the kind of anaesthesia influence complement activation and the release of inflammatory interleukins. The study design was prospective and randomised. Fifty patients undergoing open major colorectal surgery due to cancer disease or inflammatory bowel disease were studied. Twenty-five patients were given total intravenous anaesthesia (TIVA) with propofol and remifentanil, and 25 patients were given inhalational anaesthesia with sevoflurane and fentanyl. To determine complement activation (C3a and SC5b-9) and the release of pro- and anti-inflammatory interleukins (tumour necrosis factor-a (TNF-a)), interleukin-1b (IL-1b), IL-6, IL-8, IL-4 and IL-10), blood samples were drawn preoperatively, 60 minutes after start of surgery, 30 minutes after end of surgery and 24 hours postoperatively. Complement was activated and pro-inflammatory interleukins (IL-6 and IL-8) and anti-inflammatory interleukins (IL-10) were released during major colorectal surgery. There was no significant difference between TIVA and inhalational anaesthesia regarding complement activation and cytokine release. Major colorectal surgery leads to activation of the complement cascade and the release of both pro-inflammatory and anti-inflammatory cytokines. There are no significant differences between total intravenous anaesthesia (TIVA) with propofol and remifentanil and inhalational anaesthesia with sevoflurane and fentanyl regarding complement activation and the release of pro- and anti-inflammatory interleukins. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd. Scandinavian Journal of Immunology.

Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

PubMed

Shirakawa, Kotaro; Wang, Lan; Man, Na; Maksimoska, Jasna; Sorum, Alexander W; Lim, Hyung W; Lee, Intelly S; Shimazu, Tadahiro; Newman, John C; Schröder, Sebastian; Ott, Melanie; Marmorstein, Ronen; Meier, Jordan; Nimer, Stephen; Verdin, Eric

2016-05-31

Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that salicylate specifically inhibits CBP and p300 lysine acetyltransferase activity in vitro by direct competition with acetyl-Coenzyme A at the catalytic site. We used a chemical structure-similarity search to identify another anti-inflammatory drug, diflunisal, that inhibits p300 more potently than salicylate. At concentrations attainable in human plasma after oral administration, both salicylate and diflunisal blocked the acetylation of lysine residues on histone and non-histone proteins in cells. Finally, we found that diflunisal suppressed the growth of p300-dependent leukemia cell lines expressing AML1-ETO fusion protein in vitro and in vivo. These results highlight a novel epigenetic regulatory mechanism of action for salicylate and derivative drugs.

Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection

NASA Astrophysics Data System (ADS)

Kewcharoenwong, Chidchamai; Rinchai, Darawan; Utispan, Kusumawadee; Suwannasaen, Duangchan; Bancroft, Gregory J.; Ato, Manabu; Lertmemongkolchai, Ganjana

2013-11-01

Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear neutrophils (PMNs) from diabetic subjects exhibited decreased functions in response to B. pseudomallei. Here we investigated the mechanisms regulating cytokine secretion of PMNs from diabetic patients which might contribute to patient susceptibility to bacterial infections. Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide. These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

β-Sitosterol and flavonoids isolated from Bauhinia malabarica found during screening for Wnt signaling inhibitory activity.

PubMed

Park, Hyun Young; Toume, Kazufumi; Arai, Midori A; Koyano, Takashi; Kowithayakorn, Thaworn; Ishibashi, Masami

2014-01-01

Screening with a cell-based luciferase assay was conducted to identify bioactive natural products which inhibit Wnt signaling activity-guided separation of an MeOH extract of Bauhinia malabarica (Caesalpiniaceae) leaves yielded five compounds, which were identified as β-sitosterol (1), quercetin (2), 6,8-C-dimethyl kaempferol-3-O-rhamnopyranoside (3), hyperin (4), and 6,8-C-dimethyl kaempferol-3-methyl ether (5). The tested compounds 1, 3, and 5 exhibited Wnt signaling inhibitory activity, with IC50 values of 0.77, 0.74, and 16.6 μM, respectively.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance.

PubMed

Uzgören-Baran, Ayşe; Tel, Banu Cahide; Sarıgöl, Deniz; Oztürk, Elif İnci; Kazkayası, Inci; Okay, Gürol; Ertan, Mevlüt; Tozkoparan, Birsen

2012-11-01

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities and lower ulcerogenic risk, a series of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives of ibuprofen were synthesized. All compounds were evaluated for their in vivo anti-inflammatory and analgesic activities in mice. Furthermore, the ulcerogenic risks of the compounds were determined. In general, none of the compounds represent a risk for developing stomach injury as much as observed in the reference drugs ibuprofen and indomethacin. The compounds carrying a 3-phenyl-2-propenylidene (1a), (biphenyl-4-yl)methylidene (1f) and (1-methylpyrrol-2-yl)methylidene (1n) at the 6th position of the fused ring have been evaluated as potential analgesic/anti-inflammatory agents without a gastrointestinal side effect. These new compounds, therefore, deserve further attention to develop new lead drugs. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines.

PubMed

Yejella, Rajendra Prasad; Atla, Srinivasa Rao

2011-01-01

Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

A Bio-Guided Fractionation to Assess the Inhibitory Activity of Calendula officinalis L. on the NF-κB Driven Transcription in Human Gastric Epithelial Cells

PubMed Central

Colombo, Elisa; Sangiovanni, Enrico; D'Ambrosio, Michele; Bosisio, Enrica; Ciocarlan, Alexandru; Fumagalli, Marco; Guerriero, Antonio; Harghel, Petru; Dell'Agli, Mario

2015-01-01

Calendula officinalis L. has been largely known for its topical anti-inflammatory properties; however, there are no experimental evidences about its antiphlogistic effect at the gastric level. To investigate whether marigold might exert an activity against gastric inflammation, a CH2Cl2 extract obtained from C. officinalis flowers was evaluated in vitro on the NF-κB pathway. The lipophilic extract demonstrated a significant inhibitory effect on the NF-κB driven transcription. The identification of active compounds was conducted by a bio-guided fractionation of the extract that afforded 16 fractions. Fraction J exhibited a concentration-dependent inhibitory activity on the NF-κB driven transcription and significantly contributed to the antiphlogistic effect showed by CH2Cl2 extract. The main components of fraction J were loliolide and the fucoside acetates of β-eudesmol and viridiflorol. HPLC analysis of fractions D and E led to the identification and isolation of triterpene esters that showed a concentration-dependent inhibition of the NF-κB driven transcription, with faradiol-3-myristate and the corresponding aglycone being the most active compounds. The present study provides some experimental evidences that Calendula officinalis L. may exert an anti-inflammatory activity on the gastric district by the inhibition of the NF-κB system, identifying the compounds responsible, at least in part, for the observed effect. PMID:26491463

Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models.

PubMed

Hu, Fuliang; Hepburn, H R; Li, Yinghua; Chen, M; Radloff, S E; Daya, S

2005-09-14

The anti-inflammatory effects of ethanol (EEP) and water (WSD) extracts in ICR mice and Wistar rats were analyzed. Both WSD and EEP exhibited significant anti-inflammatory effects in animal models with respect to thoracic capillary vessel leakage in mice, carrageenan-induced oedema, carrageenan-induced pleurisy, acute lung damage in rats. The mechanisms for the anti-inflammatory effects probably involve decreasing prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) levels. In rats with Freund's complete adjuvant (FCA) induced arthritis, propolis extracts significantly inhibited the increase of interleukin-6 (IL-6) in inflamed tissues, but had no significant effect on levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). The results are consistent with the interpretation that EEP and WSD may exert these effects by inhibiting the activation and differentiation of mononuclear macrophages.

Anti-inflammatory effects of Houttuynia cordata supercritical extract in carrageenan-air pouch inflammation model

PubMed Central

Kim, Dajeong; Park, Dongsun; Kyung, Jangbeen; Yang, Yun-Hui; Choi, Ehn-Kyoung; Lee, Yoon-Bok; Kim, Hyun-Kyu; Hwang, Bang Yeon

2012-01-01

Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in rat carrageenan-air pouch model. Oral administration of HSE (50-200 mg/kg) suppressed carrageenan-induced exudation and albumin leakage, as well as inflammatory cell infiltration at a high dose (200 mg/kg). Intraperitoneal injection of dexamethasone (2 mg/kg) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content without influence on the cell number. HSE lowered tumor-necrosis factor-α (TNF-α) and nitric oxide (NO), as well as prostaglandin E2 (PGE2). Dexamethasone only reduced TNF-α and NO, while indomethacin decreased PGE2. The results indicate that HSE exhibits anti-inflammatory effects by inhibiting both TNF-α-NO and cyclooxygenase-2-PGE2 pathways. PMID:22787488

A prenylated flavonoid, 10-oxomornigrol F, exhibits anti-inflammatory effects by activating the Nrf2/heme oxygenase-1 pathway in macrophage cells.

PubMed

Tran, Phi-Long; Tran, Phuong Thao; Tran, Huynh Nguyen Khanh; Lee, Suhyun; Kim, Okwha; Min, Buyng-Sun; Lee, Jeong-Hyung

2018-02-01

Prenylated flavonoids are a unique class of naturally occurring flavonoids that have various pharmacological activities. In the present study, we investigated the anti-inflammatory effect in murine macrophages of a prenylated flavonoid, 10-oxomornigrol F (OMF), which was isolated from the twigs of Morus alba (Moraceae). OMF inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in RAW264.7 cells, as well as in mouse bone marrow-derived macrophages (BMMs). OMF also rescued LPS-induced septic mortality in ICR mice. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 was also significantly suppressed by OMF treatment in RAW264.7 cells. Treatment of RAW264.7 cells with OMF induced heme oxygenase (HO)-1 mRNA and protein expression and increased the nuclear translocation of the nuclear factor-E2-related factor 2 (Nrf2) as well as the expression of Nrf2 target genes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1). Treatment of RAW264.7 cells with OMF increased the intracellular level of reactive oxygen species (ROS) and the phosphorylation levels of p38 mitogen-activated protein kinase (MAPK); co-treatment with the antioxidant N-acetyl-cysteine (NAC) blocked this OMF-induced p38 MAPK phosphorylation. Moreover, NAC, or SB203580 (a p38 MAPK inhibitor), blocked the OMF-induced nuclear translocation of Nrf2 and HO-1 expression, suggesting that OMF induces HO-1 expression by activating Nrf2 through the p38 MAPK pathway. Consistent with the notion that the Nrf2/HO-1 pathway has anti-inflammatory properties, inhibiting HO-1 significantly abrogated the anti-inflammatory effects of OMF in LPS-stimulated RAW264.7 cells. Taken together, these findings suggest that OMF exerts its anti-inflammatory effect by activating the Nrf2/HO-1 pathway, and may be a potential Nrf2 activator to prevent or treat inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

The anti-inflammatory effect of Andrographis paniculata (Burm. f.) Nees on pelvic inflammatory disease in rats through down-regulation of the NF-κB pathway.

PubMed

Zou, Wei; Xiao, Zuoqi; Wen, Xiaoke; Luo, Jieying; Chen, Shuqiong; Cheng, Zeneng; Xiang, Daxiong; Hu, Jian; He, Jingyu

2016-11-25

Andrographis paniculata (Burm. f.) Nees (APN), a principal constituent of a famous traditional Chinese medicine Fukeqianjin tablet which is used for the treatment of pelvic inflammatory disease (PID), has been reported to have anti-inflammatory effect in vitro. However, whether it has pharmacological effect on PID in vivo is unclear. Therefore, the aim of this study is to test the anti-inflammatory effect of APN and illuminate a potential mechanism. Thirty-six female specific pathogen-free SD rats were randomly divided into control group, PID group, APN1 group, APN2 group, APN3 group and prednisone group. Pathogen-induced PID rats were constructed. The APN1, APN2 and APN3 group rats were orally administrated with APN extract at different levels. The prednisone group rats were administrated with prednisone. Eight days after the first infection, the histological examination of upper genital tract was carried out, and enzyme-linked immunosorbent assay (ELISA) was carried out using homogenate of the uterus and fallopian tube. Furthermore, immunohistochemical evaluations of NF-κB p65 and IκB-α in uterus was conducted. APN obviously suppressed the infiltrations of neutrophils and lymphocytes, and it could significantly reduce the excessive production of cytokines and chemokines including IL-1β, IL-6, CXCL-1, MCP-1 and RANTES in a dose-dependent manner. Furthermore, APN could block the pathogen-induced activation of NF-κB pathway. APN showed potent anti-inflammatory effect on pathogen-induced PID in rats, with a potential mechanism of inhibiting the NF-κB signal pathway.

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70*

PubMed Central

Matsuda, Minoru; Hoshino, Tatsuya; Yamashita, Yasuhiro; Tanaka, Ken-ichiro; Maji, Daisuke; Sato, Keizo; Adachi, Hiroaki; Sobue, Gen; Ihn, Hironobu; Funasaka, Yoko; Mizushima, Tohru

2010-01-01

Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, such as its inhibition of nuclear factor kappa B (NF-κB), was recently revealed. These in vitro results suggest that HSP70 protects against UVB-induced epidermal damage. Here we tested this idea by using transgenic mice expressing HSP70 and cultured keratinocytes. Irradiation of wild-type mice with UVB caused epidermal damage such as induction of apoptosis, which was suppressed in transgenic mice expressing HSP70. UVB-induced apoptosis in cultured keratinocytes was suppressed by overexpression of HSP70. Irradiation of wild-type mice with UVB decreased the cutaneous level of IκB-α (an inhibitor of NF-κB) and increased the infiltration of leukocytes and levels of pro-inflammatory cytokines and chemokines in the epidermis. These inflammatory responses were suppressed in transgenic mice expressing HSP70. In vitro, the overexpression of HSP70 suppressed the expression of pro-inflammatory cytokines and chemokines and increased the level of IκB-α in keratinocytes irradiated with UVB. UVB induced an increase in cutaneous levels of cyclobutane pyrimidine dimers and 8-hydroxy-2′-deoxyguanosine, both of which were suppressed in transgenic mice expressing HSP70. This study provides genetic evidence that HSP70 protects the epidermis from UVB-induced radiation damage. The findings here also suggest that the protective action of HSP70 is mediated by anti-apoptotic, anti-inflammatory, and anti-DNA damage effects. PMID:20018843

Compound 49b Reduces Inflammatory Markers and Apoptosis after Ocular Blast Injury

DTIC Science & Technology

2014-09-01

drug, Compound 49b, have anti-apoptotic and anti-inflammatory properties in retinal endothelial cells and in a diabetic retinopathy model [7, 10...plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Mol Vis, 2009; 15: 1418-28. 12...in other retinal damage models, specifically the streptozotocin- induced type 1 diabetic retinopathy model and retinal endothelial cells cultured in

Preparation of new Schiff bases derived from beta-enaminonitriles and hetarylcarboxaldehydes. Anti-inflammatory and ulcerogenic activities.

PubMed

Atta, S M; Ameen, A

1993-12-01

Schiff bases 3a-j were prepared by reacting the beta-enaminonitriles (1a,b) with the appropriate hetarylcarboxaldehyde, in boiling ethanol. Structural elucidations for the new compounds (3a-j) were based upon compatible analytical and spectroscopic results. Compounds 1a, 1b, 3a, 3c, 3d and 3i were tested for their anti-inflammatory and ulcerogenic activities.

A Novel Tetrasubstituted Imidazole as a Prototype for the Development of Anti-inflammatory Drugs.

PubMed

Nascimento, Marcus Vinicius P S; Munhoz, Antonio C M; Theindl, Lais C; Mohr, Eduarda Talita B; Saleh, Najla; Parisotto, Eduardo B; Rossa, Thaís A; Zamoner, Ariane; Creczynski-Pasa, Tania B; Filippin-Monteiro, Fabíola B; Sá, Marcus M; Dalmarco, Eduardo Monguilhott

2018-04-14

Although inflammation is a biological phenomenon that exists to protect the host against infections and/or related problems, its unceasing activation results in the aggravation of several medical conditions. Imidazoles, whether natural or synthetic, are molecules related to a broad spectrum of biological effects, including anti-inflammatory properties. In this study, we screened eight novel small molecules of the imidazole class synthesized by our research group for their in vitro anti-inflammatory activity. The effect of the selected molecules was confirmed in an in vivo inflammatory model. We also analyzed whether the effects were caused by inhibition of nuclear factor kappa B (NF-κB) transcription factor transmigration. Of the eight imidazoles tested, methyl 1-allyl-2-(4-fluorophenyl)-5-phenyl-1H-imidazole-4-acetate (8) inhibited nitric oxide metabolites and pro-inflammatory cytokine (TNF-α, IL-6, and IL-1β) secretion in J774 macrophages stimulated with LPS. It also attenuated leukocyte migration and exudate formation in the pleural cavity of mice challenged with carrageenan. Furthermore, imidazole 8 reverted the oxidative stress pattern triggered by carrageenan in the pleural cavity by diminishing myeloperoxidase, superoxide dismutase, catalase, and glutathione S-transferase activities and reducing the production of nitric oxide metabolites and thiobarbituric acid-reactive substances. Finally, these effects can be attributed, at least in part, to the ability of this compound to prevent NF-κB transmigration. In this context, our results demonstrate that imidazole 8 has promising potential as a prototype for the development of a new anti-inflammatory drug to treat inflammatory conditions in which NF-κB and oxidative stress play a prominent role. Graphical Abstract ᅟ.

Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans.

PubMed

d'Alessio, Patrizia A; Ostan, Rita; Bisson, Jean-François; Schulzke, Joerg D; Ursini, Matilde V; Béné, Marie C

2013-07-10

To further explore the anti-inflammatory properties of d-Limonene. A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans. Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE. In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

PubMed

Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

2012-09-01

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor

PubMed Central

Alam, Athar; Haldar, Saikat; Thulasiram, Hirekodathakallu V.; Kumar, Rahul; Goyal, Manish; Iqbal, Mohd Shameel; Pal, Chinmay; Dey, Sumanta; Bindu, Samik; Sarkar, Souvik; Pal, Uttam; Maiti, Nakul C.; Bandyopadhyay, Uday

2012-01-01

Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory reactions in various infectious and non-infectious diseases. We have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (Azadirachta indica) fruits, against MIF. Epoxyazadiradione inhibited the tautomerase activity of MIF of both human (huMIF) and malaria parasites (Plasmodium falciparum (PfMIF) and Plasmodium yoelii (PyMIF)) non-competitively in a reversible fashion (Ki, 2.11–5.23 μm). Epoxyazadiradione also significantly inhibited MIF (huMIF, PyMIF, and PfMIF)-mediated proinflammatory activities in RAW 264.7 cells. It prevented MIF-induced macrophage chemotactic migration, NF-κB translocation to the nucleus, up-regulation of inducible nitric-oxide synthase, and nitric oxide production in RAW 264.7 cells. Epoxyazadiradione not only exhibited anti-inflammatory activity in vitro but also in vivo. We tested the anti-inflammatory activity of epoxyazadiradione in vivo after co-administering LPS and MIF in mice to mimic the disease state of sepsis or bacterial infection. Epoxyazadiradione prevented the release of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, and TNF-α when LPS and PyMIF were co-administered to BALB/c mice. The molecular basis of interaction of epoxyazadiradione with MIFs was explored with the help of computational chemistry tools and a biological knowledgebase. Docking simulation indicated that the binding was highly specific and allosteric in nature. The well known MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) inhibited huMIF but not MIF of parasitic origin. In contrast, epoxyazadiradione inhibited both huMIF and plasmodial MIF, thus bearing an immense therapeutic potential against proinflammatory reactions induced by MIF of both malaria parasites and human. PMID:22645149

Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation.

PubMed

Gupta, Muskan; Kaur, Gurcharan

2018-05-30

Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwagandha (Withania somnifera) is well known for its immunomodulatory properties. The current study is an extension of our previous report on in vitro model system and was aimed to investigate anti-neuroinflammatory potential of water extract from the Ashwagandha leaves (ASH-WEX) against systemic LPS-induced neuroinflammation and associated behavioral impairments using in vivo rat model system. Oral feeding of ASH-WEX for 8 weeks significantly ameliorated the anxiety-like behavior as evident from Elevated plus maze test. Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals. NFκB, P38, and JNK MAPKs pathways analysis showed their involvement in inflammation suppression which was further confirmed by inhibitor studies. The current study provides first ever preclinical evidence and scientific validation that ASH-WEX exhibits the anti-neuroinflammatory potential against systemic LPS-induced neuroinflammation and ameliorates associated behavioral abnormalities. Aqueous extract from Ashwagandha leaves and its active phytochemicals may prove to be promising candidates to prevent neuroinflammation associated with various neuropathologies.

Synthesis of novel benzodioxane midst piperazine moiety decorated chitosan silver nanoparticle against biohazard pathogens and as potential anti-inflammatory candidate: A molecular docking studies.

PubMed

Karthik, C S; Manukumar, H M; Ananda, A P; Nagashree, S; Rakesh, K P; Mallesha, L; Qin, Hua-Li; Umesha, S; Mallu, P; Krishnamurthy, N B

2018-03-01

Nanoparticles (NPs) are currently being investigated along with the use of biodegradable polymer containing active agents in many areas of medicine for targeted applications. The present study was aimed to synthesize novel compound Benzodioxane midst piperazine (BP) and characterization of a BP decorated chitosan silver nanoparticles (BP*C@AgNPs) and shown effective against hazardous pathogens, and also having anti-inflammatory property. It was further evaluated for molecular docking proofs, and toxicity. The BP*C@AgNPs had spherical shape with size of 36.6nm with wide biocidal activity against hazardous Gram-positive and Gram-negative bacteria with excellent inhibition at 100μg/mL for S. aureus (10.08±0.05mm ZOI), and E. coli (10.03±0.04mm ZOI) compared to antibiotic Streptomycin. The anti-inflammatory activity exhibited IC 50 value of 71.61±1.05μg/mL for BP*C@AgNPs compared to indomethacin (IC 50 =40.15±1.21μg/mL). Also, the docking study of BP showed excellent score for COX1 and DNA gyrase. This in silico study confirmed the achieved efficacy of BP, with less toxicity against normal PMBCs in vitro and in vivo studies. This study concludes that, the novel synthesized BP*C@AgNPs had excellent biocidal property and as anti-inflammatory candidate revealed by docking studies, it confirms BP*C@AgNPs for first-class therapeutic applications in the area of medicinal nanotechnology for the coming days. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of wound healing and anti-inflammatory activity of the rhizomes of Rumex abyssinicus J. (Polygonaceae) in mice.

PubMed

Mulisa, Eshetu; Asres, Kaleab; Engidawork, Ephrem

2015-09-30

Rumex abyssinicus Jacq (Polygonaceae) is widely used in Ethiopia for treatment of wound and other diseases. Although reports are available in the literature on some of the claimed activities, nothing has so far been reported about the wound healing activity of R. abyssinicus. Thus, this work was initiated to investigate the wound healing and anti-inflammatory activities of 80% methanol extract of the rhizomes of R. abyssinicus in mice. Following extraction of the rhizomes of the plant with 80% methanol, the extract was formulated as ointment (5% & 10% w/w) with simple ointment base B.P. The ointment was then evaluated for wound healing activity using excision and incision wound models. Parameters, including wound contraction, epithelization time and hydroxyproline content were determined using the excision model, whereas tensile strength was measured from the incision model. In parallel, anti-inflammatory activity of the rhizome was evaluated with carrageenan induced hind paw edema model by dissolving the 80% methanol extract in 1% carboxyl methyl cellulose and administering orally in various doses (250, 500 and 750 mg/kg). Wound treated with 5% and 10% (w/w) hydroalcoholic extract ointment exhibited significant wound healing activity in both models, as evidenced by increased wound contraction, shorter epithelization time, higher tissue breaking strength and increased hydroxyproline content. The hydroalcoholic extract also produced dose-related significant reduction (p < 0.05-0.001) of inflammation. The results of this study demonstrated that the hydroalcoholic extract of the rhizomes of R. abyssinicus facilitated wound healing at least in part via its anti-inflammatory activity, supporting its traditional claim as a wound healing agent.

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review

PubMed Central

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-01-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted. PMID:26929767

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review.

PubMed

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-10-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted.

Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study.

PubMed

Pérez, David J; Díaz-Reval, M Irene; Obledo-Benicio, Fernando; Zakai, Uzma I; Gómez-Sandoval, Zeferino; Razo-Hernández, Rodrigo Said; West, Robert; Sumaya-Martínez, María Teresa; Pineda-Urbina, Kayim; Ramos-Organillo, Ángel

2017-11-05

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS • + ) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS • + . On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED 50 ) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen. Copyright © 2017 Elsevier B.V. All rights reserved.

Rauvomines A and B, Two Monoterpenoid Indole Alkaloids from Rauvolfia vomitoria.

PubMed

Zeng, Jun; Zhang, Dong-Bo; Zhou, Pan-Pan; Zhang, Qi-Li; Zhao, Lei; Chen, Jian-Jun; Gao, Kun

2017-08-04

Two unusual normonoterpenoid indole alkaloids rauvomine A (1) and rauvomine B (2), together with two known compounds peraksine (3) and alstoyunine A (4), were isolated from the aerial parts of Rauvolfia vomitoria. The structures with absolute configurations of 1 and 2 were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 is a novel C 18 normonoterpenoid indole alkaloid with a substituted cyclopropane ring that forms an unusual 6/5/6/6/3/5 hexcyclic rearranged ring system. The plausible biogenetic pathways of 1 and 2 were proposed. Compound 2 exhibited significant anti-inflammatory activity.

Bioassay-guided evaluation of anti-inflammatory and antinociceptive activities of pistachio, Pistacia vera L.

PubMed

Orhan, I; Küpeli, E; Aslan, M; Kartal, M; Yesilada, E

2006-04-21

The ethanolic and aqueous extracts prepared from different parts of Pistacia vera L. (Anacardiaceae) as well as its oleoresin were evaluated for their in vivo anti-inflammatory and antinociceptive activities. Among the extracts screened, only the oleoresin was shown to possess a marked anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage at both 250 and 500 mg/kg doses whereas the rest of the extracts were totally inactive. While the oleoresin was found to display significant antinociceptive activity at 500 mg/kg dose, the ethanolic and aqueous extracts belonging to fruit, leaf, branch and peduncle of Pistacia vera did not exhibit any noticeable antinociception in p-benzoquinone-induced abdominal contractions in mice. Fractionation of the oleoresin indicated the n-hexane fraction to be active, which further led to recognition of some monoterpenes, mainly alpha-pinene (77.5%) by capillary gas chromatography-mass spectrometry (GC-MS) as well as the oleoresin itself. alpha-Pinene was also assessed for its antinociceptive and anti-inflammatory activities in the same manner and exerted a moderate anti-inflammatory effect at 500 mg/kg dose.

Determining the pharmacological activity of Physalis peruviana fruit juice on rabbit eyes and fibroblast primary cultures.

PubMed

Pardo, Juan Manuel; Fontanilla, Marta Raquel; Ospina, Luis Fernando; Espinosa, Lady

2008-07-01

The pharmacologic activity of compounds isolated from Physalis peruviana has been demonstrated. The use of this fruit juice for treating pterygium has been reported in Colombian traditional medicine. However, studies demonstrating the fruit juice's pharmacologic activity when used in this disease have not been published to date. In the present study the anti-inflammatory and cytostatic activities of P. peruviana fruit juice in a rabbit eye inflammatory model were investigated. A novel rabbit eye inflammation model was developed for studying the juice's anti-inflammatory activity (based on an adaptation of the Draize test). Cytostatic activity was evaluated by measuring and comparing growth rates of cultured fibroblasts exposed and not exposed to various fruit juice concentrations. P. peruviana fruit juice exhibited a mild anti-inflammatory activity compared with methylprednisolone, a known anti-inflammatory drug. An interesting dose-dependent cytostatic effect on cultured fibroblasts was also established. The data found suggest that the P. peruviana fruit juice anti-pterygium effect described in traditional medicine may be related to its inhibiting fibroblast growth. The present study contributes to the pharmacologic knowledge regarding a remedy commonly used in Colombian traditional medicine.

Methyl salicylate 2-O-β-D-lactoside, a novel salicylic acid analogue, acts as an anti-inflammatory agent on microglia and astrocytes

PubMed Central

2011-01-01

Background Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer's disease (AD). Activation of microglia and astrocytes is a characteristic of brain inflammation. Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) delays the onset of AD and suppresses its progression. Methyl salicylate-2-O-β-D-lactoside (DL0309) is a new molecule chemically related to salicylic acid. The present study aimed to evaluate the anti-inflammatory effects of DL0309. Findings Our studies show that DL0309 significantly inhibits lipopolysaccharide (LPS)-induced release of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; and the expression of the inflammation-related proteins iNOS, COX-1, and COX-2 by microglia and astrocytes. At a concentration of 10 μM, DL0309 prominently inhibited LPS-induced activation of NF-κB in glial cells by blocking phosphorylation of IKK and p65, and by blocking IκB degradation. Conclusions We demonstrate here for the first time that DL0309 exerts anti-inflammatory effects in glial cells by suppressing different pro-inflammatory cytokines and iNOS/NO. Furthermore, it also regulates the NF-κB signaling pathway by blocking IKK and p65 activation and IκB degradation. DL0309 also acts as a non-selective COX inhibitor in glial cells. These studies suggest that DL0309 may be effective in the treatment of neuroinflammatory disorders, including AD. PMID:21831328

Anti-Inflammatory Effect of Spirulina platensis in Macrophages Is Beneficial for Adipocyte Differentiation and Maturation by Inhibiting Nuclear Factor-κB Pathway in 3T3-L1 Adipocytes.

PubMed

Pham, Tho X; Lee, Ji-Young

2016-06-01

We previously showed that the organic extract of a blue-green alga, Spirulina platensis (SPE), had potent anti-inflammatory effects in macrophages. As the interplay between macrophages and adipocytes is critical for adipocyte functions, we investigated the contribution of the anti-inflammatory effects of SPE in macrophages to adipogenesis/lipogenesis in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were treated with 10% conditioned medium from lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages (CMC) or LPS-stimulated, but SPE-pretreated, macrophages (CMS) at different stages of adipocyte differentiation. The expression of adipocyte differentiation markers, such as CCAAT/enhancer-binding protein α, peroxisome proliferator-activated receptor γ, and perilipin, was significantly repressed by CMC when added on day 3, while the repression was attenuated by CMS. Oil Red O staining confirmed that adipocyte maturation in CMS-treated cells, but not in CMC-treated cells, was equivalent to that of control cells. Nuclear translocation of nuclear factor κB (NF-κB) p65 was decreased by CMS compared to CMC. In lipid-laden adipocytes, CMC promoted the loss of lipid droplets, while CMS had minimal effects. Histone deacetylase 9 mRNA and protein levels were increased during adipocyte maturation, which were decreased by CMC. In conclusion, by cross-talking with adipocytes, the anti-inflammatory effects of SPE in macrophages promoted adipocyte differentiation/maturation, at least in part, by repressing the activation of NF-κB inflammatory pathways, which otherwise can be compromised in inflammatory conditions.

Anti-inflammatory effect of tricin 4′-O-(threo-β-guaiacylglyceryl) ether, a novel flavonolignan compound isolated from Njavara on in RAW264.7 cells and in ear mice edema

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

Jung, Young-Suk; Kim, Dae Hwan; Hwang, Jae Yeon

Although recent study has shown tricin 4′-O-(threo-β-guaiacylglyceryl) ether (TTGE), an isolated compound from Njavara rice, to have the most potent anti-inflammatory effects, the action mechanism has not been fully understood. Here, we examined the effect of TTGE on the inflammation and elucidated the potential mechanism. We demonstrated that TTGE significantly inhibited LPS-induced NO and ROS generation in RAW264.7 cells, which was correlated with the down-regulating effect of TTGE on the iNOS and COX-2 expression via NF-κB and STAT3. TPA-induced ear edema was also efficiently inhibited by the TTGE treatment. TTGE blocked the induction of iNOS and COX-2 through the regulationmore » of NF-κB and STAT3, which could explain the reduced TPA-induced edema symptoms. Moreover, the introduction of ERK inhibitor abrogated the anti-inflammatory effect of TTGE via the recovery of NF-κB and STAT3 signalings. Taken together, these results suggest that TTGE has anti-inflammatory properties through down-regulation of NF-κB and STAT3 pathways. - Highlights: • TTGE inhibited expression of iNOS and COX-2, NF-kB activity and ear edema through inhibition of ERK pathway.« less

Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia

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

Park, Hye Young; Department of Pharmacy, Pusan National University, Busan 609-735; Kim, Nam Deuk

2012-07-15

Diallyl disulfide (DADS), a main organosulfur component responsible for the diverse biological effects of garlic, displays a wide variety of internal biological activities. However, the cellular and molecular mechanisms underlying DADS' anti-inflammatory activity remain poorly understood. In this study, therefore, the anti-inflammatory effects of DADS were studied to investigate its potential therapeutic effects in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that pretreatment with DADS prior to treatment with LPS significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) in a dose-dependent manner. The inhibition was associated with down-regulation of inducible nitric oxide synthase (iNOS) andmore » cyclooxygenase-2 (COX-2) expression. DADS also attenuated the production of pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1) by suppressing the expression of mRNAs for these proteins. The mechanism underlying this protective effect might be related to the inhibition of nuclear factor-kappaB, Akt and mitogen-activated protein kinase signaling pathway activation in LPS-stimulated microglial cells. These findings indicated that DADS is potentially a novel therapeutic candidate for the treatment of various neurodegenerative diseases. -- Highlights: ► DADS attenuates production of NO and PGE2 in LPS-activated BV2 microglia. ► DADS downregulates levels of iNOS and COX-2. ► DADS inhibits production and expression of inflammatory cytokines and chemokine. ► DADS exhibits these effects by suppression of NF-κB, PI3K/Akt and MAPKs pathways.« less

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira.

PubMed

Hadj Ammar, Hiba; Lajili, Sirine; Ben Said, Rafik; Le Cerf, Didier; Bouraoui, Abderrahman; Majdoub, Hatem

2015-01-13

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities. The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl. The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity. The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.

Cecropia pachystachya: A Species with Expressive In Vivo Topical Anti-Inflammatory and In Vitro Antioxidant Effects

PubMed Central

Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira

2014-01-01

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β-carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms. PMID:24877079

Anti-inflammatory and analgesic activity of Peperomia pellucida (L.) HBK (Piperaceae).

PubMed

de Fátima Arrigoni-Blank, Maria; Dmitrieva, Elena G; Franzotti, Elaine Maria; Antoniolli, Angelo Roberto; Andrade, Márcio Roberto; Marchioro, Murilo

2004-04-01

An aqueous extract of the aerial part of Peperomia pellucida (L.) HBK (Piperaceae) was tested for anti-inflammatory (paw edema induced by carrageenin and arachidonic acid) and analgesic activity (abdominal writhes and hot plate) in rats and mice, respectively. Oral administration of 200 and 400 mg/kg of the aqueous extract exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis, as confirmed by the arachidonic acid test. In the abdominal writhing test induced by acetic acid, 400 mg/kg of the plant extract had the highest analgesic activity, whereas in the hot-plate test the best dose was 100 mg/kg. The LD(50) showed that Peperomia pellucida (5000 mg/kg) presented low toxicity.

Anti-inflammatory function of Withangulatin A by targeted inhibiting COX-2 expression via MAPK and NF-kappaB pathways.

PubMed

Sun, Lijuan; Liu, Jianwen; Cui, Daling; Li, Jiyu; Yu, Youjun; Ma, Lei; Hu, Lihong

2010-02-15

Withangulatin A (WA), an active component isolated from Physalis angulata L., has been reported to possess anti-tumor and trypanocidal activities in model systems via multiple biochemical mechanisms. The aim of this study is to investigate its anti-inflammatory potential and the possible underlying mechanisms. In the current study, WA significantly suppressed mice T lymphocytes proliferation stimulated with LPS in a dose- and time-dependent manner and inhibited pro-inflammation cytokines (IL-2, IFN-gamma, and IL-6) dramatically. Moreover, WA targeted inhibited COX-2 expression mediated by MAPKs and NF-kappaB nuclear translocation pathways in mice T lymphocytes, and this result was further confirmed by the COX-1/2 luciferase reporter assay. Intriguingly, administration of WA inhibited the extent of mice ear swelling and decreased pro-inflammatory cytokines production in mice blood serum. Based on these evidences, WA influences the mice T lymphocytes function through targeted inhibiting COX-2 expression via MAPKs and NF-kappaB nuclear translocation signaling pathways, and this would make WA a strong candidate for further study as an anti-inflammatory agent. (c) 2009 Wiley-Liss, Inc.

Substituted galacturonan from starfruit: Chemical structure and antinociceptive and anti-inflammatory effects.

PubMed

Leivas, Carolina L; Nascimento, Leandro F; Barros, Wellinghton M; Santos, Adair R S; Iacomini, Marcello; Cordeiro, Lucimara M C

2016-03-01

Starfruit (Averrhoa carambola L.) is an edible tropical fruit, which is usually consumed as a fresh table fruit or as fruit juice. It also exhibits various pharmacological activities. In this study, polysaccharides were extracted with boiling water and purified by freeze-thawing and Fehling treatments. After purification steps, a homogenous fraction was obtained. It was analyzed by sugar composition, gel permeation chromatography, methylation, and two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy analyses. It comprised arabinose (Ara), galactose (Gal), and galacturonic acid (GalA) in a molar ratio of 12.3:1.7:86.0. Methylation and NMR spectroscopy analyses showed that it contained a substituted galacturonan composed of (1→4)-linked α-D-Galp A units branched at O-2 by (1→5)-linked α-L-Araf and terminal α-L-Araf and α-D-Galp A units. The effect of PFSCW (10-300mg/kg, i.p.) on nocifensive behavior induced by intraplantar injection of formalin in mice was evaluated. The fraction demonstrated antinociceptive and anti-inflammatory properties, suggesting that it may be useful in therapeutic intervention for the management of inflammatory pain. Copyright © 2015. Published by Elsevier B.V.

The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

PubMed Central

Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

2014-01-01

The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves

PubMed Central

Yasmen, Nelufar; Tajmim, Afsana; Akter, Mst. Irin; Hazra, Amit Kumar; Rahman, S. M. Mushiur

2018-01-01

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition (⁎P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant (⁎P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine. PMID:29599807

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves.

PubMed

Yasmen, Nelufar; Aziz, Md Abdullah; Tajmim, Afsana; Akter, Mst Irin; Hazra, Amit Kumar; Rahman, S M Mushiur

2018-01-01

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition ( ⁎ P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant ( ⁎ P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine.

Artemisia asiatica ethanol extract exhibits anti-photoaging activity.

PubMed

Jeong, Deok; Lee, Jongsung; Jeong, Seong-Gu; Hong, Yo Han; Yoo, Sulgi; Han, Sang Yun; Kim, Ji Hye; Kim, Sunggyu; Kim, Jin Sic; Chung, Young Soo; Kim, Jong-Hoon; Yi, Young-Su; Cho, Jae Youl

2018-06-28

Artemisia asiatica Nakai is a traditional herbal plant that has long been used in anti-inflammatory, anti-infective and skin protective remedies. In this study, traditionally known skin-protective activity of Artemisia asiatica Nakai was examined with its ethanol extract (Aa-EE) under various photoaging conditions using skin-originated cells, and the underlying mechanism was also examined using various types of cells. Effects of Aa-EE on cell viability, photocytotoxicity, and expression of matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, and moisturizing factors were measured in B16F10, HEK293, NIH3T3, and HaCaT cells under untreated and ultraviolet B (UVB)-irradiation conditions. Anti-melanogenic effect of Aa-EE was also examined by measuring both melanin content in B16F10 cells and tyrosinase activity. Anti-photoaging mechanism of Aa-EE was explored by determining the activation levels of signaling molecules by immunoblotting analysis. Aa-EE protected HaCaT cells from UVB irradiation-induced death. Aa-EE increased the expression of a type 1 pro-collagen gene and decreased the expression of matrix metalloproteinases, and COX-2 in NIH3T3 cells induced by UVB. Aa-EE increased the expression of transglutamase-1, hyaluronic acid synthase (HAS)-2, and HAS-3 in HaCaT cells and decreased the production of melanin in α-melanocyte-stimulating hormone-stimulated B16F10 cells by suppressing tyrosinase activity and the expression of tyrosinase, microphthalmia-associated transcription factor, tyrosinase-related protein (TRP)-1 and TRP-2. The results suggest that Aa-EE could be skin-protective remedy with anti-photoaging, anti-apoptotic, skin remodeling, moisturizing, and anti-melanogenesis properties. Copyright © 2018 Elsevier B.V. All rights reserved.

Transformation of Lactuca sativa L. with rol C gene results in increased antioxidant potential and enhanced analgesic, anti-inflammatory and antidepressant activities in vivo.

PubMed

Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Sajid, Moniba; Kayani, Waqas Khan; Mirza, Bushra

2016-12-01

Lettuce is an important edible crop which possesses various medicinal properties. In this study Lactuca sativa L. (cv Grand Rapids) was transformed by Agrobacterium-mediated transformation with rol C gene. Transgene integration and expression was confirmed through PCR and semiquantitative RT-PCR. The transformed extracts were evaluated for their in vitro antioxidant and in vivo analgesic, anti-inflammatory and antidepressant activities in rats. The transformed plants showed 53-98 % increase in total phenolic and 45-58 % increase in total flavonoid contents compared with untransformed plants. Results of total reducing power and total antioxidant capacity exhibited 90-118 and 61-75 % increase in transformed plants, respectively. In contrast to control, DPPH, lipid peroxidation and DNA protection assay showed up to 37, 20 and 50 % enhancement in transformed plants, respectively. The extracts showed similar but significant enhancement behavior in hot plate analgesic and carrageenan-induced hind paw edema test. The transformed extracts showed 72.1 and 78.5 % increase for analgesic and anti-inflammatory activities, respectively. The transformants of rol C gene exhibited prominent antidepressant activity with 64-73 % increase compared with untransformed plants. In conclusion, the present work suggests that transformation with rol C gene can be used to generate lettuce with enhanced medicinally important properties, such as antioxidant, analgesic, anti-inflammatory and antidepressant potential.

New cytotoxic and anti-inflammatory compounds isolated from Morus alba L.

PubMed

Qin, Jing; Fan, Min; He, Juan; Wu, Xing-De; Peng, Li-Yan; Su, Jia; Cheng, Xiao; Li, Yan; Kong, Ling-Mei; Li, Rong-Tao; Zhao, Qin-Shi

2015-01-01

Six Diels-Alder adducts (1-6) and nine prenylated flavanones (7-15) were isolated from the root bark of Morus alba L. Among them, soroceal B (1) and sanggenol Q (7) were new compounds. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques. Compounds 1-3, 9, 10, 12, 13 and 15 exhibited cytotoxic activity against five human tumour lines and compound 2 inhibited significantly selective cytotoxic activities towards HL-60 and AGS cells with IC50 of 3.4 and 3.6 μM. Compounds 3, 5, 9 and 12 exhibited moderate inhibitory activity against nitric oxide production in LPS-activated RAW264.7.

Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant and Anti-Inflammatory Properties of a Stilbenoid-Rich Root Extract of Vitis vinifera

PubMed Central

Esatbeyoglu, Tuba; Ewald, Philipp; Yasui, Yoshiaki; Yokokawa, Haruka; Wagner, Anika E.; Matsugo, Seiichi; Winterhalter, Peter; Rimbach, Gerald

2016-01-01

Dietary stilbenoids are receiving increasing attention due to their potential health benefits. However, most studies concerning the bioactivity of stilbenoids were conducted with pure compounds, for example, resveratrol. The aim of this study was to characterize a complex root extract of Vitis vinifera in terms of its free radical scavenging and cellular antioxidant and anti-inflammatory properties. HPLC-ESI-MS/MS analyses of the root extract of Vitis vinifera identified seven stilbenoids including two monomeric (resveratrol and piceatannol), two dimeric (trans-ɛ-viniferin and ampelopsin A), one trimeric (miyabenol C), and two tetrameric (r-2-viniferin = vitisin A and r-viniferin = vitisin B) compounds which may mediate its biological activity. Electron spin resonance and spin trapping experiments indicate that the root extract scavenged 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, galvinoxyl, and superoxide free radicals. On a cellular level it was observed that the root extract of Vitis vinifera protects against hydrogen peroxide-induced DNA damage and induces Nrf2 and its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. Furthermore, the root extract could induce the antiatherogenic hepatic enzyme paraoxonase 1 and downregulate proinflammatory gene expression (interleukin 1β, inducible nitric oxide synthase) in macrophages. Collectively our data suggest that the root extract of Vitis vinifera exhibits free radical scavenging as well as cellular antioxidant and anti-inflammatory properties. PMID:26788254

Qingfei Xiaoyan Wan, a traditional Chinese medicine formula, ameliorates Pseudomonas aeruginosa–induced acute lung inflammation by regulation of PI3K/AKT and Ras/MAPK pathways

PubMed Central

Hou, Yuanyuan; Nie, Yan; Cheng, Binfeng; Tao, Jin; Ma, Xiaoyao; Jiang, Min; Gao, Jie; Bai, Gang

2016-01-01

Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan (QF), a traditional Chinese medicine (TCM) formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa–induced acute pneumonia in mice were evaluated. The mechanisms by which four typical anti-inflammatory ingredients from QF, arctigenin (ATG), cholic acid (CLA), chlorogenic acid (CGA) and sinapic acid (SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines (TNF-α and IL-6) and chemokines (IL-8 and RANTES), reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively. PMID:27175332

Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.

PubMed

Abrego, Guadalupe; Alvarado, Helen; Souto, Eliana B; Guevara, Bessy; Bellowa, Lyda Halbaut; Parra, Alexander; Calpena, Ana; Garcia, María Luisa

2015-09-01

Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels. Copyright © 2015 Elsevier B.V. All rights reserved.

ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action

PubMed Central

Lee, Jeong-Oog; Kim, Mi-Yeon

2015-01-01

Luteolin is a flavonoid identified as a major anti-inflammatory component of Artemisia asiatica. Numerous reports have demonstrated the ability of luteolin to suppress inflammation in a variety of inflammatory conditions. However, its exact anti-inflammatory mechanism has not been fully elucidated. In the present study, the anti-inflammatory mode of action in activated macrophages of luteolin from Artemisia asiatica was examined by employing immunoblotting analysis, a luciferase reporter gene assay, enzyme assays, and an overexpression strategy. Luteolin dose-dependently inhibited the secretion of nitric oxide (NO) and prostaglandin E2 (PGE2) and diminished the levels of mRNA transcripts of inducible NO synthase (iNOS), tumor necrosis factor- (TNF-) α, and cyclooxygenase-2 (COX-2) in lipopolysaccharide- (LPS-) and pam3CSK-treated macrophage-like RAW264.7 cells without displaying cytotoxicity. Luteolin displayed potent NO-inhibitory activity and also suppressed the nuclear translocation of NF-κB (p65 and p50) via blockade of Src and Syk, but not other mitogen-activated kinases. Overexpression of wild type Src and point mutants thereof, and molecular modelling studies, suggest that the ATP-binding pocket may be the luteolin-binding site in Src. These results strongly suggest that luteolin may exert its anti-inflammatory action by suppressing the NF-κB signaling cascade via blockade of ATP binding in Src and Syk. PMID:26236111

Anti-inflammatory and anti-bacterial activity, and cytotoxicity of halloysite surfaces.

PubMed

Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Palacios, Eduardo; Montoya, José Ascención; Gómez-Vidales, Virginia; Ramírez-Apán, María Teresa

2013-11-01

Halloysite is a naturally-occurring nanomaterial occurring in the thousands of tons and that serves as biomaterial, with applications in the areas of biotechnology, pharmaceutical, and medical research. This study reports on the anti-inflammatory, cytotoxic, and anti-oxidant activity of halloysite Jarrahdale (collected at ∼ 45 km SE of Perth, Western Australia; JA), Dragon Mine (provided by Natural Nano Inc., Rochester, New York; NA), and Kalgoorie Archean (collected at Siberia, ∼ 85km NW of Kalgoorlie, West Australia; PA). Prior to biological testing, halloysites were characterized by 27Al and 29Si Nuclear Magnetic Resonance Spectroscopy, the anti-inflammatory activity was determined by (a) the mouse ear edema method, using 12-o-tetradecanoylphorbol-13-acetate (TPA) as anti-inflammatory agent; and (b) the myeloperoxidase enzymatic activity method (MPO). Cell viability was determined using the MTT method. Sample characterization by NMR method showed similar symmetry and atomic environments, with no evidence of distortion(s) due to shiftings in atomic ordering or electron density. The anti-inflammatory activity followed the order: PA>JA>NA, and remained invariant with time. Prolonged anti-inflammatory activity related inversely to surface area and lumen space. The low extent of infiltration at shorter reaction times confirmed a limiting number of active surface sites. EPR intensity signals followed the order: JA>NA>PA. The poor stabilization of RO species in PA suspensions was explained by tube alignment provoking occlusion, thus limiting transfer of H(+) or e(-) from-and-to the surface, and decreases in acidity associated to Al(oct). Cell viability (%) varied from one surface to the other, PA(92.3 ± 6.0), JA(84.9 ± 7.8), and NA(78.0 ± 5.6), but related directly to SBET values. Copyright © 2013 Elsevier B.V. All rights reserved.

Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats.

PubMed

Chen, Wei-Cheng; Liou, Shorong-Shii; Tzeng, Thing-Fong; Lee, Shiow-Ling; Liu, I-Min

2012-11-23

Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE) was investigated for its healing efficiency in a rat excision wound model. Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w) LJEE ointment, or the reference standard drug, 0.2% (w/w) nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing. LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w) LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w) LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production. The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair.

Seagrass as a potential source of natural antioxidant and anti-inflammatory agents.

PubMed

Yuvaraj, N; Kanmani, P; Satishkumar, R; Paari, A; Pattukumar, V; Arul, V

2012-04-01

Halophila spp. is a strong medicine against malaria and skin diseases and is found to be very effective in early stages of leprosy. Seagrasses are nutraceutical in nature and therefore of importance as food supplements. The antibacterial, antioxidant, and anti-inflammatory activities of Halophila ovalis R. Br. Hooke (Hydrocharitaceae) methanol extract were investigated and the chemical constituents of purified fractions were analyzed. Plant materials were collected from Pondicherry coastal line, and antimicrobial screening of crude extract, and purified fractions was carried out by the disc diffusion method and the minimum inhibitory concentration (MICs) of the purified fractions and reference antibiotics were determined by microdilution method. Antioxidant and anti-inflammatory activities were investigated in vitro. Chemical constituents of purified fractions V and VI were analyzed by gas chromatography-mass spectrometry (GC-MS), and the phytochemicals were quantitatively determined. Methanol extract inhibited the growth of Bacillus cereus at a minimum inhibitory concentration of 50 µg/mL and other Gram-negative pathogens at 75 µg/ml, except Vibrio vulnificus. Reducing power and total antioxidant level increased with increasing extract concentration. H. ovalis exhibited strong scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals at IC(50) of 0.13 and 0.65 mg/mL, respectively. Methanol extract of H. ovalis showed noticeable anti-inflammatory activity at IC(50) of 78.72 µg/mL. The GC-MS analysis of H. ovalis revealed the presence of triacylglycerols as major components in purified fractions. Quantitative analysis of phytochemicals revealed that phenols are rich in seagrass H. ovalis. These findings demonstrated that the methanol extract of H. ovalis exhibited appreciable antibacterial, noticeable antioxidant, and anti-inflammatory activities, and thus could be use as a potential source for natural health products.

Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats

PubMed Central

2012-01-01

Background Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE) was investigated for its healing efficiency in a rat excision wound model. Methods Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w) LJEE ointment, or the reference standard drug, 0.2% (w/w) nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing. Results LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w) LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w) LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production. Conclusions The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair. PMID:23173654

Bupleurum chinense extract ameliorates an OVA-induced murine allergic asthma through the reduction of the Th2 and Th17 cytokines production by inactivation of NFκB pathway.

PubMed

Bui, Thi Tho; Piao, Chun Hua; Song, Chang Ho; Shin, Hee Soon; Chai, Ok Hee

2017-07-01

Bupleurum chinense belongs to the Bupleurum spp. family that has been used in traditional herbal medicine for over thousand years. It has been reported to have anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic, anti-fibrotic and immunomodulatory effect. However, the effect of B. Chinense on allergic asthma remains unclear. This study investigated the immunomodulatory effects of B. Chinense extracts (BCE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we evaluated the number of total cells, differential inflammatory cells and the production of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung homogenate as well as histological structure. The levels of NFκB p65, IκBα, p-NFκB p65, p-IκBα and the total immunoglobulin (Ig) E, anti-OVA IgE, anti-OVA IgG were also examined. The oral administration of 200mg/kg BCE inhibited the accumulation of inflammatory cells especially eosinophils in BALF. Also, BCE regulated the imbalance of Th1, Th2 and Th17-related production, with attenuated the expression of GATA3, IL-1β, IL-4, IL-5, IL-6, TNF-α and RORγt, IL-17A in BALF and lung homogenate, meanwhile, up-regulated the secretion of INF-γ in lung homogenate. The levels of IgE, anti-OVA IgE, anti-OVA IgG1 and anti-OVA IgG2a were also suppressed by BCE treatment in serum. Futhermore, BCE inhibited the proinflammatory cytokines via inactivation of NFκB p65 phosphorylation and IκBα degradation in cytoplasm. The histological analysis showed that the infiltration of inflammatory cells, mucus hypersecretion and collagen fiber deposits were ameliorated in BCE treated mice. In addition, BCE induced the functional differentiation of naive CD4+ T cells forward to Th1 and Tr1 through producing INF-γ and IL-10. These results suggest that BCE may have therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 cytokines production by inactivation of NFκB pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Nutritional agents with anti-inflammatory properties in chemoprevention of colorectal neoplasia.

PubMed

Hull, Mark A

2013-01-01

The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer (CRC). Several naturally occurring substances with anti-inflammatory properties, used in a purified 'nutraceutical' form, including omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and polyphenols such as curcumin and resveratrol, have been demonstrated to have anti-CRC activity in preclinical models. As expected, these agents have an excellent safety and tolerability profile in Phase II clinical trials. Phase III randomized clinical trials of these naturally occurring substances are now beginning to be reported. The omega-3 polyunsaturated fatty acid EPA, in the free fatty acid (FFA) form, has been demonstrated to reduce adenomatous polyp number and size in patients with familial adenomatous polyposis (FAP), a finding which has prompted evaluation of this formulation of EPA for prevention of 'sporadic' colorectal neoplasia. Anti-inflammatory 'nutraceuticals' require further clinical evaluation in polyp prevention trials as they exhibit many of the characteristics of the ideal cancer chemoprevention agent, including safety, tolerability and patient acceptability.

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro

PubMed Central

Liu, Lihua; Zuo, Zhongfu; Lu, Sijing; Liu, Aihua; Liu, Xuezheng

2017-01-01

Objective(s): Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Materials and Methods: Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo. Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro. Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro. Results: Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Conclusion: Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR. PMID:28852447

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro.

PubMed

Liu, Lihua; Zuo, Zhongfu; Lu, Sijing; Liu, Aihua; Liu, Xuezheng

2017-07-01

Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo . Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro . Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro . Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR.

Dihydro-CDDO-trifluoroethyl amide suppresses inflammatory responses in macrophages via activation of Nrf2

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

Li, Bin; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208; Abdalrahman, Akram

2014-02-21

Highlights: • Dh404 suppresses the expression of a selected set of pro-inflammatory cytokines in inflamed macrophages via activating Nrf2. • Dh404 activates Nrf2 while keeping Keap1 function intact in macrophages. • Dh404 minimally regulates NF-κB pathway in macrophages. - Abstract: Nuclear factor erythroid 2-related factor (Nrf2) is the major regulator of cellular defenses against various pathological stresses in a variety of organ systems, thus Nrf2 has evolved to be an attractive drug target for the treatment and/or prevention of human disease. Several synthetic oleanolic triterpenoids including dihydro-CDDO-trifluoroethyl amide (dh404) appear to be potent activators of Nrf2 and exhibit chemopreventive promisesmore » in multiple disease models. While the pharmacological efficacy of Nrf2 activators may be dependent on the nature of Nrf2 activation in specific cell types of target organs, the precise role of Nrf2 in mediating biological effects of Nrf2 activating compounds in various cell types remains to be further explored. Herein we report a unique and Nrf2-dependent anti-inflammatory profile of dh404 in inflamed macrophages. In lipopolysaccharide (LPS)-inflamed RAW264.7 macrophages, dh404 dramatically suppressed the expression of pro-inflammatory cytokines including inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β), while minimally regulating the expression of interleulin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNFα). Dh404 potently activated Nrf2 signaling; however, it did not affect LPS-induced NF-κB activity. Dh404 did not interrupt the interaction of Nrf2 with its endogenous inhibitor Kelch-like ECH associating protein 1 (Keap1) in macrophages. Moreover, knockout of Nrf2 blocked the dh404-induced anti-inflammatory responses in LPS-inflamed macrophages. These results demonstrated that dh404 suppresses pro-inflammatory responses in macrophages via an activation of Nrf2 independently of Keap1 and NF-κB, suggesting a unique therapeutic potential of dh404 for specific targeting a Nrf2-mediated resolution of inflammation.« less

In vitro biological activity and essential oil composition of four indigenous South African Helichrysum species.

PubMed

Lourens, A C U; Reddy, D; Başer, K H C; Viljoen, A M; Van Vuuren, S F

2004-12-01

Helichrysum species are used widely to treat various medical conditions. In this study, the anti-microbial, anti-oxidant (DPPH assay) and anti-inflammatory activity (5-lipoxygenase assay) of Helichrysum dasyanthum, Helichrysum felinum, Helichrysum excisum and Helichrysum petiolare were investigated. The essential oil compositions of these species were determined. The acetone and methanol extracts as well as the essential oils exhibited activity against Gram-positive bacteria, while both the methanol and acetone extracts of all four species were active in the anti-oxidant assay. The essential oils, on the other hand, displayed activity in the 5-lipoxygenase assay, which was used as an indication of anti-inflammatory activity. Two extracts exhibited promising activity in the anti-microbial assay, the acetone extract of Helichrysum dasyanthum with a MIC value of 15.63 microg/ml and the methanol extract of Helichrysum excisum with a MIC value of 62.5 microg/ml. The acetone extract of Helichrysum dasyanthum was the most active free radical scavenger in the DPPH assay (IC(50) of 9.53 microg/ml) while values for the anti-inflammatory activity of the essential oils ranged between 25 and 32 microg/ml. The essential oil compositions of three species (Helichrysum dasyanthum, Helichrysum excisum and Helichrysum petiolare) were dominated by the presence of monoterpenes such as alpha-pinene, 1,8-cineole and p-cymene. In the oil of Helichrysum felinum, monoterpenes were largely absent. Its profile consisted of a variety of sesquiterpenes in low concentrations with beta-caryophyllene dominating.

Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism.

PubMed

Birrell, M A; McCluskie, K; Wong, S; Donnelly, L E; Barnes, P J; Belvisi, M G

2005-05-01

Consumption of a naturally occurring polyphenol, resveratrol, in particular through drinking moderate amounts of red wine, has been suggested to be beneficial to health. A plethora of in vitro studies published demonstrate various anti-inflammatory actions of resveratrol. The aim of this research was to determine whether any of these anti-inflammatory effects translate in vivo in a rodent model of LPS induced airway inflammation. Resveratrol reduced lung tissue neutrophilia to a similar magnitude as that achieved by treatment with budesonide. This was associated with a reduction in pro-inflammatory cytokines and prostanoid levels. Interestingly, the reduction did not appear to be due to an impact on NF-kappaB activation or the expression of the respective genes as suggested by various in vitro publications. These results suggest that resveratrol may possess anti-inflammatory properties via a novel mechanism. Elucidation of this mechanism may lead to potential new therapies for the treatment of chronic inflammation.

Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory Response In Vitro and In Vivo

PubMed Central

Cha, Ji Young; Jung, Ji Yun; Jung, Jae Yup; Lee, Jong Rok; Cho, Il Je; Ku, Sae Kwang; Byun, Sung Hui; Ahn, Yong-Tae; Lee, Chul Won; Kim, Sang Chan; An, Won G.

2013-01-01

Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)) and nuclear factor-kappa B (NF-κB) as well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-) induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75, and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2, iNOS, NF-κB, and MAPKs as well as production of prostaglandin E2 (PGE2), nitric oxide (NO), IL-6, and TNF-α induced by LPS. Our results demonstrate that PWS possesses anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the signaling pathways of NF-κB and MAPKs in LPS-induced macrophage cells. More importantly, results of the carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In addition, it is considered that PWS also inhibits the acute edematous inflammations through suppression of mast cell degranulations and inflammatory mediators, including COX-2, iNOS and TNF-α. Thus, our findings may provide scientific evidence to explain the anti-inflammatory properties of PWS in vitro and in vivo. PMID:23533508

Antimicrobial and anti-inflammatory potential therapy for opportunistic microorganisms.

PubMed

Assaf, Areej M; Amro, Bassam I; Mashallah, Sundus; Haddadin, Randa N

2016-05-31

Methanolic extracts of six plants (Arbutus andrachne, Chrysanthemum coronarium, Inula viscosa, Origanum syriacum, Punica granatum, and Rosmarinus officinalis) used in traditional medicine for the treatment of bacterial and fungal infections were evaluated. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of some medicinal plants in lowering the risk of opportunistic infections of the oral cavity caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Extracts were evaluated separately and in a mixture. The methanolic plant extracts were tested against three opportunistic microorganisms by determining the minimum inhibitory concentration (MIC). They were also evaluated for their ability to suppress the release of the pro-inflammatory cytokine IL-6 while not suppressing the release of the anti-inflammatory cytokine IL-10 from peripheral blood mononuclear cells using ELISA. All extracts showed both antimicrobial and anti-inflammatory activities. However, O. syriacum exhibited the highest antimicrobial activity for the three microorganisms among all of the tested extracts (MIC S. aureus: 1 mg/mL; P. aeruginosa: 2 mg/mL; and C. albicans: 1 mg/mL). The extracts inhibited the expression of the pro-inflammatory cytokine IL-6 with apparent dose-dependent responses while they attenuated the secretion of the anti-inflammatory cytokine IL-10. The mixture of O. syriacum and R. officinalis showed an anti-inflammatory effect, with a synergistic antimicrobial effect. These findings support the idea that a diet rich in plants and herbs may contribute to the reduction of inflammation and microbial growth and may also be preventive against various infections, including those related to the oral cavity.

Flavonoid Fraction of Bergamot Juice Reduces LPS-Induced Inflammatory Response through SIRT1-Mediated NF-κB Inhibition in THP-1 Monocytes

PubMed Central

Risitano, Roberto; Currò, Monica; Cirmi, Santa; Ferlazzo, Nadia; Campiglia, Pietro; Caccamo, Daniela; Ientile, Riccardo; Navarra, Michele

2014-01-01

Plant polyphenols exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory genes. Recently, Citrus bergamia has been studied as a natural source of bioactive molecules with antioxidant activity, but few studies have focused on molecular mechanisms underlying their potential beneficial effects. Several findings have suggested that polyphenols could influence cellular function by acting as activators of SIRT1, a nuclear histone deacetylase, involved in the inhibition of NF-κB signaling. On the basis of these observations we studied the anti-inflammatory effects produced by the flavonoid fraction of the bergamot juice (BJe) in a model of LPS-stimulated THP-1 cell line, focusing on SIRT1-mediated NF-κB inhibition. We demonstrated that BJe inhibited both gene expression and secretion of LPS-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by a mechanism involving the inhibition of NF-κB activation. In addition, we showed that BJe treatment reversed the LPS-enhanced acetylation of p65 in THP-1 cells. Interestingly, increasing concentrations of Sirtinol were able to suppress the inhibitory effect of BJe via p65 acetylation, underscoring that NF-κB–mediated inflammatory cytokine production may be directly linked to SIRT1 activity. These results suggest that BJe may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process. PMID:25260046

Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-γ.

PubMed

Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

2015-01-15

Citral, a component of lemongrass oil, has been reported to have many pharmacological activities such as anti-bacterial and anti-inflammatory effects. However, the effects of citral on acute lung injury (ALI) and the molecular mechanisms have not been reported. The aim of this study was to detect the effects of citral on lipopolysaccharide (LPS)-induced acute lung injury and investigate the molecular mechanisms. LPS-induced acute lung injury model was used to detect the anti-inflammatory effect of citral in vivo. The alveolar macrophages were used to investigate the molecular mechanism of citral in vitro. The results showed that pretreatment with citral remarkably attenuated pulmonary edema, histological severities, TNF-α, IL-6 and IL-1β production in LPS-induced ALI in vivo. In vitro, citral inhibited LPS-induced TNF-α, IL-6 and IL-1β production in alveolar macrophages. LPS-induced NF-κB activation was also inhibited by citral. 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, this is the first to demonstrate that citral protects LPS-induced ALI in mice. The anti-inflammatory mechanism of citral is associated with activating PPAR-γ, thereby inhibiting LPS-induced inflammatory response. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative inhibitory effects of magnolol, honokiol, eugenol and bis-eugenol on cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7 macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis.

PubMed

Murakami, Yukio; Kawata, Akifumi; Seki, Yuya; Koh, Teho; Yuhara, Kenji; Maruyama, Takehisa; Machino, Mamoru; Ito, Shigeru; Kadoma, Yoshinori; Fujisawa, Seiichiro

2012-01-01

The anti-inflammatory activity of magnolol and related compounds is currently a focus of interest. In the present study, the inhibitory effects of these compounds on cyclooxygenase (COX-2) expression and nuclear factor-kappa B (NF-κB) activation were investigated in RAW264.7 macrophage-like cells stimulated with the fimbriae of Porphyromonas gingivalis, an oral anaerobe. The cytotoxicity of magnolol, honokiol, eugenol and bis-eugenol against RAW264.7 cells was determined using a cell counting kit (CCK-8). The regulatory effect of these compounds on the expression of COX-2 mRNA, stimulated by exposure to the fimbriae was investigated by real-time polymerase chain reaction (PCR). NF-κB activation was evaluated by enzyme-linked immunosorbent assay (ELISA)-like microwell colorimetric transcription factor activity assay (Trans-AM) and western blot analysis. The radical-scavenging activity was determined using the induction period method in the methyl methacrylate-azobisisobutyronitrile (AIBN) polymerization system under nearly anaerobic conditions. The phenolic bond dissociation enthalpy (BDE) and orbital energy were calculated at the density functional theory (DFT) B3LYP/6-31G* level. The cytotoxicity against RAW264.7 cells declined in the order bis-eugenol>eugenol> honokiol>magnolol, whereas the radical-scavenging activity declined in the order honokiol, bis-eugenol>magnolol> eugenol. Magnolol and honokiol significantly inhibited the fimbria-induced expression of COX-2 at non-cytotoxic concentrations. Both the fimbria-stimulated binding of NF-κB to its consensus sequence and phosphorylation-dependent proteolysis of inhibitor κB-α were markedly inhibited by magnilol and honokiol, whereas eugenol and bis-eugenol did not inhibit COX-2 expression and NF-κB activation. Magnolol and honokiol possessed a high electronegativity (χ) value. Magnolol and honokiol exhibit antioxidative activity, low cytotoxicity, and anti-inflammatory activity. These compounds may be capable of preventing chronic inflammatory diseases induced by oral bacteria.

Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages

PubMed Central

Mortaz, Esmaeil; Adcock, Ian M.; Ricciardolo, Fabio L. M.; Varahram, Mohammad; Jamaati, Hamidreza; Velayati, Ali Akbar; Folkerts, Gert; Garssen, Johan

2015-01-01

Background Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development of ‘allergic asthma’ in animals but their effects in COPD are unknown. Objective To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation. Design We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation. Results Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05). Conclusions This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD. PMID:26317628

Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages.

PubMed

Mortaz, Esmaeil; Adcock, Ian M; Ricciardolo, Fabio L M; Varahram, Mohammad; Jamaati, Hamidreza; Velayati, Ali Akbar; Folkerts, Gert; Garssen, Johan

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development of 'allergic asthma' in animals but their effects in COPD are unknown. To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation. We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation. Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05). This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD.

Synthesis, anti-inflammatory evaluation in vivo and docking studies of some new 5-(benzo[b]furan-2-ylmethyl)-6-methyl-pyridazin-3(2H)-one derivatives

NASA Astrophysics Data System (ADS)

Boukharsa, Youness; Lakhlili, Wiame; El harti, Jaouad; Meddah, Bouchra; Tiendrebeogo, Ramata Yvette; Taoufik, Jamal; El Abbes Faouzi, My; Ibrahimi, Azeddine; Ansar, M'hammed

2018-02-01

Seven novel 5-(benzo[b]furan-2-ylmethyl)-6-methyl-pyridazin-3(2H)-one derivatives (6a to 6g) have been synthesized by the condensation of appropriate 3-(benzofuran-2-ylmethylene)-4-oxopentanoic acid and hydrazine hydrate in ethanol. Structures of all compounds were elucidated by elemental analysis, IR, 1H NMR and 13C NMR. These compounds were tested for their anti-inflammatory activity in carrageenan-induced rat paw edema model. In silico molecular docking study has been executed to study the binding interactions of the synthesized compounds with COX-2 protein. Compounds 6a, 6b, 6e and 6g showed a good anti-inflammatory activity at 50 mg/kg compared with the indometacin at 10 mg/kg and the aspirin at 150 mg/kg and good binding affinity with COX-2.

Magnolol inhibits LPS-induced inflammatory response in uterine epithelial cells : magnolol inhibits LPS-induced inflammatory response.

PubMed

Luo, Jia; Xu, Yanwen; Zhang, Minfang; Gao, Ling; Fang, Cong; Zhou, Canquan

2013-10-01

Endometritis is an inflammation of the uterine lining that is commonly initiated at parturition. The uterine epithelial cells play an important role in defending against invading pathogens. Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been shown to have anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effect of magnolol in modifying lipopolysaccharide (LPS)-induced signal pathways in mouse uterine epithelial cells. We found that magnolol inhibited TNF-α and IL-6 production in LPS-stimulated mouse uterine epithelial cells. We also found that magnolol inhibited LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK, and P38. Furthermore, magnolol could significantly inhibit the expression of TLR4 stimulating by LPS. These results suggest that magnolol exerts an anti-inflammatory property by downregulating the expression of TLR4 upregulated by LPS, thereby attenuating TLR4-mediated NF-κB and MAPK signaling and the release of pro-inflammatory cytokines. These findings suggest that magnolol may be a therapeutic agent against endometritis.

Anti-inflammatory effect of miltirone on inflammatory bowel disease via TLR4/NF-κB/IQGAP2 signaling pathway.

PubMed

Wang, Hongjian; Gu, Junfei; Hou, Xuefeng; Chen, Juan; Yang, Nan; Liu, Ying; Wang, Gang; Du, Mei; Qiu, Huihui; Luo, Yi; Jiang, Ziyu; Feng, Liang

2017-01-01

Inflammatory bowel disease (IBD) is characterized by a radical imbalance in the activation of proinflammatory and anti-inflammatory signaling pathways in the gut. This study was conducted to evaluate the anti-inflammation effect of miltirone against IBD in vitro and in vivo, and try to explore the underlying mechanisms. Miltirone could extenuate the loss of colon length and weight caused by TNBS. Additionally, macroscopic scores and DAI were reduced significantly compared with the TNBS group. The levels of TNF-α, IL-1β, IL-6 and IL-8 were increased significantly with the induction by TNBS (100mg/kg) or LPS (0.5mg/mL). Interestingly, miltirone could down-regulate the levels of these increased pro-inflammatory factors in a dose-dependent manner both in vivo and in vitro. The protein and mRNA expressions of TLR4, MyD88, NF-κB p65 were up-regulated by TNBS or LPS stimulation. CRX-526, the TLR4 inhibitor, as well as miltirone could significantly suppress the increased protein and mRNA expressions. Miltirone could up-regulate the descreased IQGAP2 expression induced by LPS. All these revealed that the anti-inflammatory effect of miltirone on IBD may be via regulating TLR4/NF-κB/IQGAP2 signaling pathway. The findings might supply beneficial hints for the drug research to cure the IBD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Tanshinone II A stabilizes vulnerable plaques by suppressing RAGE signaling and NF-κB activation in apolipoprotein-E-deficient mice

PubMed Central

Zhao, Dong; Tong, Lufang; Zhang, Lixin; Li, Hong; Wan, Yingxin; Zhang, Tiezhong

2016-01-01

Tanshinone II A (TSIIA) is a diterpene quinone extracted from the roots of Salvia miltiorrhiza with anti-inflammatory and anti-oxidant properties that is used to treat atherosclerosis. In the current study, morphological analyses were conducted to evaluate the effects of TSIIA on atherosclerotic vulnerable plaque stability. Additionally, receptor of advanced glycation end products (RAGE), adhesion molecule, and matrix-metalloproteinases (MMPs) expression, and nuclear factor-κB (NF-κB) activation were examined in apolipoprotein E (apoE)-deficient mice treated with TSIIA. Eight-week-old apoE−/− mice were administered TSIIA and fed an atherogenic diet for 8 weeks. TSIIA exhibited no effects on plaque size. Analysis of the vulnerable plaque composition demonstrated decreased numbers of macrophages and smooth muscle cells, and increased collagen content in apoE-deficient mice treated with TSIIA compared with untreated mice. Western blotting revealed that TSIIA downregulated the expression levels of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and MMP-2, −3, and −9, suppressed RAGE, and inhibited NF-κB, JNK and p38 activation. The present study demonstrated that the underlying mechanism of TSIIA stabilization of vulnerable plaques involves interfering with RAGE and NF-κB activation, and downregulation of downstream inflammatory factors, including ICAM-1, VCAM-1, and MMP-2, −3 and −9 in apoE−/− mice. PMID:27840935

Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

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

Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi

HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrolmore » induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction.« less

HILIC quantification of oenotheralanosterol A and B from Oenothera biennis and their suppression of IL-6 and TNF-α expression in mouse macrophages.

PubMed

Singh, Rashmi; Trivedi, Priyanka; Bawankule, Dnyaneshwar Umrao; Ahmad, Ateeque; Shanker, Karuna

2012-05-07

Evening primrose (Oenothera biennis L.) is a wild medicinal herb of Central American origin that is now globally widespread. Its traditional uses include treatment of rheumatoid arthritis and premenopausal pain both of which have an inflammatory component. The present study demonstrates the in vitro anti-inflammatory activity of three Oenothera biennis compounds. Oenotheralanosterol A and B (Oen-A & Oen-B) along with gallic acid (GA) were isolated and characterized using column chromatography and NMR. The compounds were tested with LPS stimulated peritoneal mouse macrophages assaying for suppression of IL-6, TNF-α and NO synthesis. An HILIC method for the simultaneous quantitation of GA, Oen-A, and Oen-B in Oenothera biennis plant material was also developed as a means of monitoring quality of plant material. Significant inhibition of TNF-α and IL-6 by GA, Oen-A and Oen-B was observed (p<0.05). Inhibition was concentration dependent and no synergistic or antagonistic effect on pro-inflammatory cytokines was found when used in combination (1:1) (p>0.05). The HILIC analysis method was validated using Oenothera biennis root. The study demonstrates the anti-inflammatory activity of Oenothera biennis root compounds and supports its traditional use in arthritis management. Active anti-inflammatory compounds were identified and quantified by the HILIC method. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.