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Sample records for cyclooxygenase-2 generates anti-inflammatory

  1. In situ click chemistry generation of cyclooxygenase-2 inhibitors.

    PubMed

    Bhardwaj, Atul; Kaur, Jatinder; Wuest, Melinda; Wuest, Frank

    2017-12-01

    Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.

  2. Therapeutic window for cyclooxygenase-2 related anti-inflammatory therapy after status epilepticus

    PubMed Central

    Jiang, Jianxiong; Yang, Myung-Soon; Quan, Yi; Gueorguieva, Paoula; Ganesh, Thota; Dingledine, Raymond

    2015-01-01

    As a prominent inflammatory effector of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) mediates brain inflammation and injury in many chronic central nervous system (CNS) conditions including seizures and epilepsy, largely through its receptor subtype EP2. However, EP2 receptor activation might also be neuroprotective in models of excitotoxicity and ischemia. These seemingly incongruent observations expose the delicacy of immune and inflammatory signaling in the brain, thus the therapeutic window for quelling neuroinflammation might vary with injury type and target molecule. Here, we identify a therapeutic window for EP2 antagonism to reduce delayed mortality and functional morbidity after status epilepticus (SE) in mice. Importantly, treatment must be delayed relative to SE onset to be effective, a finding that could be explained by the time-course of COX-2 induction after SE and compound pharmacokinetics. A large number of inflammatory mediators were upregulated in hippocampus after SE with COX-2 and IL-1β temporally leading many others. Thus, EP2 antagonism represents a novel anti-inflammatory strategy to treat SE with a tightly-regulated therapeutic window. PMID:25600211

  3. Anti-inflammatory effects of essential oils from Chamaecyparis obtusa via the cyclooxygenase-2 pathway in rats.

    PubMed

    An, Beum-Soo; Kang, Ji-Houn; Yang, Hyun; Jung, Eui-Man; Kang, Hong-Seok; Choi, In-Gyu; Park, Mi-Jin; Jeung, Eui-Bae

    2013-07-01

    Essential oils are concentrated hydrophobic liquids containing volatile aromatic compounds from plants. In the present study, the essential oil of Chamaecyparis obtusa (C. obtusa), which is commercially used in soap, toothpaste and cosmetics, was extracted. Essential oil extracted from C. obtusa contains several types of terpenes, which have been shown to have anti-oxidative and anti-inflammatory effects. In the present study, we examined the anti-inflammatory effects of C. obtusa essential oil in vivo and in vitro following the induction of inflammation by lipopolysaccharides (LPS) in rats. While LPS induced an inflammatory response through the production of prostaglandin E2 (PGE2) in the blood and peripheral blood mononuclear cells (PMNCs), these levels were reduced when essential oil was pre-administered. Additionally, the mechanism of action underlying the anti-inflammatory effects of C. obtusa essential oil was investigated by measuring the mRNA expression of inflammation‑associated genes. LPS treatment significantly induced the expression of transforming growth factor α (TNFα) and cyclooxygenase-2 (COX-2) in rats, while C. obtusa essential oil inhibited this effect. Taken together, our results demonstrate that C. obtusa essential oil exerts anti‑inflammatory effects by regulating the production of PGE2 and TNFα gene expression through the COX-2 pathway. These findings suggest that C. obtusa essential oil may constitute a novel source of anti-inflammatory drugs.

  4. Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2

    PubMed Central

    Hegde, Pushpa; Maddur, Mohan S.; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srini V.

    2011-01-01

    Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2. PMID:22028854

  5. Comparison of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors use in Australia and Nova Scotia (Canada)

    PubMed Central

    Barozzi, Nadia; Sketris, Ingrid; Cooke, Charmaine; Tett, Susan

    2009-01-01

    AIMS Cyclooxygenase-2 (COX-2) inhibitors were marketed aggressively and their rapid uptake caused safety concerns and budgetary challenges in Canada and Australia. The objectives of this study were to compare and contrast COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drug (ns-NSAID) use in Nova Scotia (Canada) and Australia and to identify lessons learned from the two jurisdictions. METHODS Ns-NSAID and COX-2 inhibitor Australian prescription data (concession beneficiaries) were downloaded from the Medicare Australia website (2001–2006). Similar Pharmacare data were obtained for Nova Scotia (seniors and those receiving Community services). Defined daily doses per 1000 beneficiaries day−1 were calculated. COX-2 inhibitors/all NSAIDs ratios were calculated for Australia and Nova Scotia. Ns-NSAIDs were divided into low, moderate and high risk for gastrointestinal side-effects and the proportions of use in each group were determined. Which drugs accounted for 90% of use was also calculated. RESULTS Overall NSAID use was different in Australia and Nova Scotia. However, ns-NSAID use was similar. COX-2 inhibitor dispensing was higher in Australia. The percentage of COX-2 inhibitor prescriptions over the total NSAID use was different in the two countries. High-risk NSAID use was much higher in Australia. Low-risk NSAID prescribing increased in Nova Scotia over time. The low-risk/high-risk ratio was constant throughout over the period in Australia and increased in Nova Scotia. CONCLUSIONS There are significant differences in Australia and Nova Scotia in use of NSAIDs, mainly due to COX-2 prescribing. Nova Scotia has a higher proportion of low-risk NSAID use. Interventions to provide physicians with information on relative benefits and risks of prescribing specific NSAIDs are needed, including determining their impact. PMID:19660008

  6. Steroidal and non-steroidal cyclooxygenase-2 inhibitor anti-inflammatory drugs as pre-emptive medication in patients undergoing periodontal surgery.

    PubMed

    Peres, Maria Fernanda Santos; Ribeiro, Fernanda Vieira; Ruiz, Karina Gonzalez Silvério; Nociti-Jr, Francisco Humberto; Sallum, Enilson Antônio; Casati, Márcio Zaffalon

    2012-01-01

    The aim of the present study was to compare the pre-emptive use of a cyclooxygenase-2 (COX-2) inhibitor with a well established steroidal anti-inflammatory drug for pain and edema relief following periodontal surgery for crown lengthening. Thirty patients requiring periodontal surgery were randomly assigned to receive one of the following medications: selective COX-2 inhibitor or steroidal anti-inflammatory drug, 60 min before the surgical procedure. To examine patient anxiety, a Corah's dental anxiety scale was applied before surgery. Using a visual analog scale, the extent of pain/discomfort during the trans-operative period and immediately after the surgery was measured. Additionally, intensity of pain/discomfort and edema were examined 4, 8, 12 and 24 h postoperatively. With regard to anxiety, no statistical differences between the groups were observed (p>0.05). With respect to the extent of pain/discomfort during the trans-operative, immediate and late postoperative period, data demonstrated no significant differences (p>0.05) between the COX-2 inhibitor and steroidal groups. With regard to edema, intragroup analysis did not reveal any statistically significant difference (p>0.05) during the 24 h following surgery in either group. In conclusion, both anti-inflammatory drugs presented a similar potential for pain and edema relief following periodontal surgery.

  7. Cyclooxygenase-2 selective and nitric oxide-releasing nonsteroidal anti-inflammatory drugs and gastric mucosal responses.

    PubMed

    Takeuchi, K; Suzuki, K; Yamamoto, H; Araki, H; Mizoguchi, H; Ukawa, H

    1998-12-01

    Occurrence of gastrointestinal damage and delayed healing of pre-existing ulcer are commonly observed in association with clinical use of nonsteroidal antiinflammatory drugs (NSAIDs). We examined the effects of NS-398, the cyclooxygenase (COX)-2 selective inhibitor, and nitric oxide (NO)- releasing aspirin (NCX-4016) on gastric mucosal ulcerogenic and healing responses in experimental animals, in comparison with those of nonselective COX inhibitors such as indomethacin and aspirin. Indomethacin and aspirin given orally were ulcerogenic by themselves in rat stomachs, while either NS-398 or NCX-4016 was not ulcerogenic at the doses which exert the equipotent antiinflammatory action with indomethacin or aspirin. Among these NSAIDs, only NCX-4016 showed a dose-dependent protection against gastric lesions induced by HCl/ethanol in rats. On the other hand, the healing of gastric ulcers induced in mice by thermal-cauterization was significantly delayed by repeated administration of these NSAIDs for more than 7 days, except NCX-4016. Gastric mucosal prostaglandin contents were reduced by indomethacin, aspirin and NCX-4016 in both normal and ulcerated mucosa, while NS-398 significantly decreased prostaglandin generation only in the ulcerated mucosa. Oral administration of NCX-4016 in pylorus-ligated rats and mice increased the levels of NO metabolites in the gastric contents. In addition, both NS-398 and NCX-4016 showed an equipotent anti-inflammatory effect against carrageenan-induced paw edema in rats as compared with indomethacin and aspirin. These results suggest that both indomethacin and aspirin are ulcerogenic by themselves and impair the healing of pre-existing gastric ulcers as well. The former action is due to inhibition of COX-1, while the latter effect may be accounted for by inhibition of COX-2 and mimicked by NS-398, the COX-2 selective NSAID. NCX-4016, despite inhibiting both COX-1 and COX-2, protects the stomach against damage and preserves the healing

  8. δ-Amyrone, a specific inhibitor of cyclooxygenase-2, exhibits anti-inflammatory effects in vitro and in vivo of mice.

    PubMed

    Niu, Xiaofeng; Yao, Huan; Li, Weifeng; Mu, Qingli; Li, Huani; Hu, Hua; Li, Yongmei; Huang, Huimin

    2014-07-01

    The whole plant of Sedum lineare Thunb has been used as traditional folk medicines for the treatment of sore throat, persistent hepatitis, jaundice and dysentery. δ-Amyrone (13(18)-Oleanen-3-one), a pentacyclic triterpene compound from S. lineare Thunb, was found to possess a potent anti-inflammatory effect in different inflammation model animals. Pretreatment with δ-Amyrone (i.p.) inhibited the ear edema in xylene-induced mouse ear edema. δ-Amyrone also decreased the level of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and leukocyte numbers in acetic acid-induced peritonitis in vivo. To clarify the possible mechanism of δ-Amyrone, we investigated the effect of δ-Amyrone in lipopolysaccharide (LPS) induced peritoneal macrophages. The data indicated that δ-Amyrone notably inhibited IL-6, TNF-α and NO production. In addition, the result showed that δ-Amyrone may control the cyclooxygenase-2 (COX-2) regulation and not the cyclooxygenase-1 (COX-1) at protein levels. These results suggest that δ-Amyrone is a bioactive agent which possesses anti-inflammatory effects, which may be relevant to the regulation of COX-2.

  9. Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer.

    PubMed

    Moon, Chang Mo; Kwon, Ji-Hee; Kim, Ji Suk; Oh, Sun-Hee; Jin Lee, Kyoung; Park, Jae Jun; Pil Hong, Sung; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho

    2014-02-01

    Cancer stem cells (CSCs) play a pivotal role in cancer relapse or metastasis. We investigated the CSC-suppressing effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and the relevant mechanisms in colorectal cancer. We measured the effect of NSAIDs on CSC populations in Caco-2 or SW620 cells using colosphere formation and flow cytometric analysis of PROM1 (CD133)(+) CD44(+) cells after indomethacin treatment with/without prostaglandin E2 (PGE2) or peroxisome proliferator-activated receptor γ (PPARG) antagonist, and examined the effect of indomethacin on transcriptional activity and protein expression of NOTCH/HES1 and PPARG. These effects of indomethacin were also evaluated in a xenograft mouse model. NSAIDs (indomethacin, sulindac and aspirin), celecoxib, γ-secretase inhibitor and PPARG agonist significantly decreased the number of colospheres formation compared to controls. In Caco-2 and SW620 cells, compared to controls, PROM1 (CD133)(+) CD44(+) cells were significantly decreased by indomethacin treatment, and increased by 5-fluorouracil (5-FU) treatment. This 5-FU-induced increase of PROM1 (CD133)(+) CD44(+) cells was significantly attenuated by combination with indomethacin. This CSC-inhibitory effect of indomethacin was reversed by addition of PGE2 and PPARG antagonist. Indomethacin significantly decreased CBFRE and increased PPRE transcriptional activity and their relative protein expressions. In xenograft mouse experiments using 5-FU-resistant SW620 cells, the 5-FU treatment combined with indomethacin significantly reduced tumor growth, compared to 5-FU alone. In addition, treatment of indomethacin alone or combination of 5-FU and indomethacin decreased the expressions of PROM1 (CD133), CD44, PTGS2 (cyclooxygenase 2) and HES1, and increased PPARG expression. NSAIDs could selectively reduce the colon CSCs and suppress 5-FU-induced increase of CSCs via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1, and activating PPARG.

  10. Non-steroidal anti-inflammatory drugs, Cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia

    PubMed Central

    Barozzi, Nadia; Tett, Susan E

    2008-01-01

    Background Cross national drug utilization studies can provide information about different influences on physician prescribing. This is important for medicines with issues around safety and quality of use, like non selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors. To enable comparison of prescription medicine use across different jurisdictions with a range of population sizes, data first need to be compared within Australia to understand whether use in a smaller sub-population may be considered as representative of the total use within Australia. The aim of this study was to compare the utilization of non selective NSAID, COX-2 inhibitors and paracetamol between Queensland and Australia. Method Dispensing data were obtained for concession beneficiaries for Australia for ns-NSAIDs, COX-2 inhibitors and paracetamol subsidized by the PBS over the period 1997–2003. The same data were purchased for Queensland. Data were converted to Defined Daily Dose (DDD)/1000 beneficiaries/day (World Health Organization anatomical therapeutic chemical classification, 2005). Results Total NSAID and paracetamol consumption were similar in Australia and Queensland. Ns-NSAID use decreased sharply with the introduction of COX-2 inhibitors (from approximately 80 to 40 DDD/1000 beneficiaries/day). Paracetamol was constant (approximately 45 DDD/1000 beneficiaries/day). COX-2 inhibitors consumption was initially higher in Queensland than in the whole of Australia. Conclusion Despite initial divergence in celecoxib use between Queensland and Australia, the use of ns-NSAIDs, COX-2 inhibitors and paracetamol overall, in concession beneficiaries, was comparable in Australia and Queensland. PMID:18816393

  11. Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide.

    PubMed

    Inomata, Naoko; Osuna, Hiroyuki; Yamaguchi, Junko; Onoda, Masahito; Takeshita, Yoshihiro; Chiba, Yoshiyuki; Kambara, Takeshi; Ikezawa, Zenro

    2007-03-01

    The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.

  12. Feijoa sellowiana Berg fruit juice: anti-inflammatory effect and activity on superoxide anion generation.

    PubMed

    Monforte, Maria T; Fimiani, Vincenzo; Lanuzza, Francesco; Naccari, Clara; Restuccia, Salvatore; Galati, Enza M

    2014-04-01

    Feijoa sellowiana Berg var. coolidge fruit juice was studied in vivo for the anti-inflammatory activity by carrageenin-induced paw edema test and in vitro for the effects on superoxide anion release from neutrophils in human whole blood. The fruit juice was analyzed by the high-performance liquid chromatography method, and quercetin, ellagic acid, catechin, rutin, eriodictyol, gallic acid, pyrocatechol, syringic acid, and eriocitrin were identified. The results showed a significant anti-inflammatory activity of F. sellowiana fruit juice, sustained also by an effective antioxidant activity observed in preliminary studies on 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. In particular, the anti-inflammatory activity edema inhibition is significant since the first hour (44.11%) and persists until the fifth hour (44.12%) of the treatment. The effect on superoxide anion release was studied in human whole blood, in the presence of activators affecting neutrophils by different mechanisms. The juice showed an inhibiting response on neutrophils basal activity in all experimental conditions. In stimulated neutrophils, the higher inhibition of superoxide anion generation was observed at concentration of 10(-4) and 10(-2) mg/mL in whole blood stimulate with phorbol-myristate-13-acetate (PMA; 20% and 40%) and with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 15% and 48%). The significant reduction of edema and the inhibition of O2(-) production, occurring mainly through interaction with protein-kinase C pathway, confirm the anti-inflammatory effect of F. sellowiana fruit juice.

  13. Generation of innovative anti-inflammatory and anti-arthritic glucocorticoid derivatives that release NO: the nitro-steroids.

    PubMed

    Perretti, M; Paul-Clark, M J; Mancini, L; Flower, R J

    2003-05-01

    Addition to the prednisolone structure of a chemical moiety (linker+nitric ester) that releases NO species yielded a novel glucocorticoid (nitro-prednisolone or NCX-1015) with enhanced anti-inflammatory activities. Nitro-prednisolone was much more potent than prednisolone and the derivative devoid of the nitric ester in an acute peritonitis model (higher impact on neutrophil migration and soluble mediator generation) as well as in models of chronic inflammation (air-pouch granuloma and collagen II-induced arthritis). In the collagen II-induced arthritis model, NCX-1015 abrogated the plasma levels of a catabolite of cartilage and bone metabolism, indication of a disease modifying action. In an in vitro assay of bone resorption, NCX-1015 did not activate osteoclast activity, whereas prednisolone did. This lack of effect of NCX-1015 was chiefly due to NO. We propose that NCX-1015 is the prototype of a new class of glucocorticoids, the nitro-steroids, endowed with enhanced anti-inflammatory properties and reduced side effects. These and other experimental observations here reviewed may prompt the assessment of the clinical impact of the nitro-steroids on rheumatoid arthritis and inflammatory bowel disease.

  14. Synthesis and anti-inflammatory evaluation of N-sulfonyl anthranilic acids via Ir(III)-catalyzed C-H amidation of benzoic acids.

    PubMed

    Han, Sang Hoon; Suh, Hyo Sun; Jo, Hyeim; Oh, Yongguk; Mishra, Neeraj Kumar; Han, Sangil; Kim, Hyung Sik; Jung, Young Hoon; Lee, Byung Mu; Kim, In Su

    2017-03-29

    The iridium(III)-catalyzed ortho-C-H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of N-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vitro anti-inflammatory activity against interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds 4c and 4d, generated from p-OMe- and p-Br-sulfonyl azides, were found to display potent anti-inflammatory property stronger than that of well-known NSAIDs ibuprofen.

  15. Anti-inflammatory activity of Taraxacum officinale.

    PubMed

    Jeon, Hye-Jin; Kang, Hyun-Jung; Jung, Hyun-Joo; Kang, Young-Sook; Lim, Chang-Jin; Kim, Young-Myeong; Park, Eun-Hee

    2008-01-04

    Taraxacum officinale has been widely used as a folkloric medicine for the treatment of diverse diseases. The dried plant was extracted with 70% ethanol to generate its ethanol extract (TEE). For some experiments, ethyl acetate (EA), n-butanol (BuOH) and aqueous (Aq) fractions were prepared in succession from TEE. TEE showed a scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, a diminishing effect on intracellular reactive oxygen species (ROS) level, and an anti-angiogenic activity in the chicken chorioallantoic (CAM) assay. In the carrageenan-induced air pouch model, TEE inhibited production of exudate, and significantly diminished nitric oxide (NO) and leukocyte levels in the exudate. It also possessed an inhibitory effect on acetic acid-induced vascular permeability and caused a dose-dependent inhibition on acetic acid-induced abdominal writhing in mice. Suppressive effects of TEE on the production of NO and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Among the fractions, the n-butanol fraction (BuOH) was identified to be most effective in the CAM assay. Collectively, Taraxacum officinale contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities through its inhibition of NO production and COX-2 expression and/or its antioxidative activity.

  16. Antihistaminic, Anti-Inflammatory, and Antiallergic Properties of the Nonsedating Second-Generation Antihistamine Desloratadine: A Review of the Evidence

    PubMed Central

    Blaiss, Michael

    2011-01-01

    Abstract: The allergy cascade presents widespread inflammatory and proinflammatory activation, robust cytokine and chemokine signaling, and heterogeneous immune and endothelial responses that lead ultimately to the manifestations of allergic reaction. Histamine, a small peptide with inherent vasoactive properties, is released from granules contained within mast cells, basophils, lymphocytes, and other reservoirs and interacts with histamine receptors to regulate numerous cellular functions involved in allergic inflammation and immune modulation. Of the known histamine receptors, the H1-receptor is most clearly associated with potentiation of proinflammatory immune cell activity and enhanced effector function and is the prime focus of suppressive therapy. Second-generation oral H1-antihistamines, such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine, are mainstays of allergy treatment, acting as highly specific, long-acting H1-receptor agonists at its unique receptor. The ongoing identification of immune effector cells and mediators involved in the allergic cascade indicates that further research is necessary to define the role of antihistamines such as desloratadine in anti-inflammatory therapy. PMID:23268457

  17. Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes.

    PubMed

    Delmastro-Greenwood, Meghan; Hughan, Kara S; Vitturi, Dario A; Salvatore, Sonia R; Grimes, George; Potti, Gopal; Shiva, Sruti; Schopfer, Francisco J; Gladwin, Mark T; Freeman, Bruce A; Gelhaus Wendell, Stacy

    2015-12-01

    A gap in our understanding of the beneficial systemic responses to dietary constituents nitrate (NO3(-)), nitrite (NO2(-)) and conjugated linoleic acid (cLA) is the identification of the downstream metabolites that mediate their actions. To examine these reactions in a clinical context, investigational drug preparations of (15)N-labeled NO3(-) and NO2(-) were orally administered to healthy humans with and without cLA. Mass spectrometry analysis of plasma and urine indicated that the nitrating species nitrogen dioxide was formed and reacted with the olefinic carbons of unsaturated fatty acids to yield the electrophilic fatty acid, nitro-cLA (NO2-cLA). These species mediate the post-translational modification (PTM) of proteins via reversible Michael addition with nucleophilic amino acids. The PTM of critical target proteins by electrophilic lipids has been described as a sensing mechanism that regulates adaptive cellular responses, but little is known about the endogenous generation of fatty acid nitroalkenes and their metabolites. We report that healthy humans consuming (15)N-labeled NO3(-) or NO2(-), with and without cLA supplementation, produce (15)NO2-cLA and corresponding metabolites that are detected in plasma and urine. These data support that the dietary constituents NO3(-), NO2(-) and cLA promote the further generation of secondary electrophilic lipid products that are absorbed into the circulation at concentrations sufficient to exert systemic effects before being catabolized or excreted.

  18. Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged Black Garlic Extracts.

    PubMed

    Jeong, Yi Yeong; Ryu, Ji Hyeon; Shin, Jung-Hye; Kang, Min Jung; Kang, Jae Ran; Han, Jaehee; Kang, Dawon

    2016-03-30

    Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh raw garlic (FRG) extract (FRGE). In addition, we investigated which components are responsible for the observed effects. Hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging activities and low ROS generation in RAW264.7 cells compared with FRGE. However, inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was stronger than that by ABGE. FRGE reduced PGE₂, NO, IL-6, IL-1β, LTD₄, and LTE₄ production in LPS-activated RAW264.7 cells more than did ABGE. The combination of FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant in ABGE than in FRGE, decreased the anti-inflammatory activity compared with FRGE. FRGE-induced inhibition of NF-κB activation and pro-inflammatory gene expression was blocked by combination with sugars. The lower anti-inflammatory activity in ABGE than FRGE could result from the presence of sugars. Our results suggest that ABGE might be helpful for the treatment of diseases mediated predominantly by ROS.

  19. Synthesis and biological evaluation of new heteroaryl carboxylic acid derivatives as anti-inflammatory-analgesic agents.

    PubMed

    Abouzid, Khaled Abouzid Mohamed; Khalil, Nadia Abdalla; Ahmed, Eman Mohamed; Zaitone, Sawsan Abo-Bakr

    2013-01-01

    A series of nicotinic acid derivatives structurally related to niflumic acid and certain pyridazine-containing compounds have been synthesized and characterized by analytical and spectral data. All compounds were screened for their potential analgesic and anti-inflammatory activities. The compounds which displayed analgesic and anti-inflammatory activities were tested for ulcerogenicity and screened for in vivo inhibition of certain inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Compounds 1c, 2a, 2b, and 5a have shown potent analgesic and anti-inflammatory activities.

  20. Anti-inflammatory activity of constituents isolated from Terminalia chebula ***waiting for publication date

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was aimed at the evaluation of the anti-inflammatory activity of twelve compounds isolated from the methanolic extract of fruits of Terminalia chebula. The activity was determined in terms of their ability to inhibit inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in L...

  1. Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside.

    PubMed

    Jung, Hyun Ah; Jin, Seong Eun; Min, Byung-Sun; Kim, Byung-Woo; Choi, Jae Sue

    2012-06-01

    The anti-inflammatory activity of whole Cirsium maackii (family Compositae) plants and of its major flavonoid, luteolin 5-O-glucoside, was evaluated for their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression, and tert-butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS) generation in RAW 264.7 murine macrophage cells. The methanolic extract of C. maackii showed strong anti-inflammatory activity, and was thus fractionated with several solvents. The ethyl acetate-soluble fraction, exhibiting the highest anti-inflammatory activity potential, was further to yield a major flavonoid, luteolin 5-O-glucoside. We found that luteolin 5-O-glucoside, at a non-toxic concentration, inhibited LPS-induced NO production and t-BHP-induced ROS generation in a dose-dependent manner in RAW 264.7 cells. It also suppressed the expression of iNOS and COX-2 in LPS-stimulated macrophages. Furthermore, the efficacies of the methanolic extract of C. maackii in inhibiting both NO and ROS were attributed to its flavonoid content by HPLC analysis. These results indicated that C. maackii whole plants and its flavonoids inhibit the expression of iNOS and COX-2 in through the inhibition of ROS generation, and therefore can be considered as a useful therapeutic and preventive approach for the treatment of various inflammatory and oxidative stress-related diseases.

  2. Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes.

    PubMed

    Boodram, Janine N; Mcgregor, Iain J; Bruno, Peter M; Cressey, Paul B; Hemann, Michael T; Suntharalingam, Kogularamanan

    2016-02-18

    The breast cancer stem cell (CSC) potency of a series of copper(II)-phenanthroline complexes containing the nonsteroidal anti-inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4, selectivity kills breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC-specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis.

  3. Analysis of antioxidant and anti-inflammatory activity of silicon in murine macrophages.

    PubMed

    Kim, Eun-Jin; Bu, So-Young; Sung, Mi-Kyung; Kang, Myung-Hwa; Choi, Mi-Kyeong

    2013-12-01

    The purpose of this study is to investigate the antioxidant and anti-inflammatory properties of silicon (Si) in the RAW 264.7 murine macrophage cell line. Lipopolysaccharide (LPS) was used to induce inflammatory conditions, and cells were treated with 0, 1, 5, 10, 25, 50, and 100 μM Si in the form of sodium metasilicate. Tert-butylhydroquinone (TBHQ), a well-known antioxidative substance, was used as a positive control to assess the degree of antioxidative and anti-inflammatory properties of Si. Sodium metasilicate at 100 μM suppressed LPS-induced nitric oxide generation from macrophages 36 h after treatment. In addition, 50 μM sodium metasilicate decreased interleukin-6 production, and the degree of suppression was comparable to that of 10 μM TBHQ treatment. LPS-induced messenger RNA (mRNA) expression of tumor necrosis factor-α and inducible nitric oxide synthase was significantly decreased by 1, 5, 10, and 50 μM sodium metasilicate. Cyclooxygenase-2 mRNA expression was also suppressed by 1, 5, 25, and 50 μM sodium metasilicate. Based on these data, Si has the ability to suppress the production of inflammatory cytokines and mediators, possibly through the suppression of radical scavenger activity and down-regulation of gene expression of inflammatory mediators.

  4. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

  5. H2S dependent and independent anti-inflammatory activity of zofenoprilat in cells of the vascular wall.

    PubMed

    Monti, Martina; Terzuoli, Erika; Ziche, Marina; Morbidelli, Lucia

    2016-11-01

    Cardiovascular diseases as atherosclerosis are associated to an inflammatory state of the vessel wall which is accompanied by endothelial dysfunction, and adherence and activation of circulating inflammatory cells. Hydrogen sulfide, a novel cardiovascular protective gaseous mediator, has been reported to exert anti-inflammatory activity. We have recently demonstrated that the SH containing ACE inhibitor zofenoprilat, the active metabolite of zofenopril, controls the angiogenic features of vascular endothelium through H2S enzymatic production by cystathionine gamma lyase (CSE). Based on H2S donor/generator property of zofenoprilat, the objective of this study was to evaluate whether zofenoprilat exerts anti-inflammatory activity in vascular cells through its ability to increase H2S availability. Here we found that zofenoprilat, in a CSE/H2S-mediated manner, abolished all the inflammatory features induced by interlukin-1beta (IL-1β) in human umbilical vein endothelial cells (HUVEC), especially the NF-κB/cyclooxygenase-2 (COX-2)/prostanoid biochemical pathway. The pre-incubation with zofenoprilat/CSE dependent H2S prevented IL-1β induced paracellular hyperpermeability through the control of expression and localization of cell-cell junctional markers ZO-1 and VE-cadherin. Moreover, zofenoprilat/CSE dependent H2S reduced the expression of the endothelial markers CD40 and CD31, involved in the recruitment of circulating mononuclear cells and platelets. Interestingly, this anti-inflammatory activity was also confirmed in vascular smooth muscle cells and fibroblasts as zofenoprilat reduced, in both cell lines, proliferation, migration and COX-2 expression induced by IL-1β, but independently from the SH moiety and H2S availability. These in vitro data document the anti-inflammatory activity of zofenoprilat on vascular cells, reinforcing the cardiovascular protective effect of this multitasking drug.

  6. Anti-Inflammatory, Antioxidant, Anti-Angiogenic and Skin Whitening Activities of Phryma leptostachya var. asiatica Hara Extract

    PubMed Central

    Jung, Hyun-Joo; Cho, Young-Wook; Lim, Hye-Won; Choi, Hojin; Ji, Dam-Jung; Lim, Chang-Jin

    2013-01-01

    This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine. PMID:24009862

  7. Antibacterial and Anti-Inflammatory Activities of Physalis Alkekengi var. franchetii and Its Main Constituents

    PubMed Central

    Shu, Zunpeng; Xing, Na; Wang, Qiuhong; Li, Xinli; Xu, Bingqing; Li, Zhenyu; Kuang, Haixue

    2016-01-01

    This study was designed to determine whether the 50% EtOH fraction from AB-8 macroporous resin fractionation of a 70% EtOH extract of P. Alkekengi (50-EFP) has antibacterial and/or anti-inflammatory activity both in vivo and in vitro and to investigate the mechanism of 50-EFP anti-inflammatory activity. Additionally, this study sought to define the chemical composition of 50-EFP. Results indicated that 50-EFP showed significant antibacterial activity in vitro and efficacy in vivo. Moreover, 50-EFP significantly reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interleukin 6 (IL-6) production in lipopolysaccharide- (LPS-) stimulated THP-1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) in THP-1 cells were suppressed by 50-EFP, which inhibited nuclear translocation of p65. Consistent with this anti-inflammatory activity in vitro, 50-EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50-EFP. Our data demonstrate that 50-EFP has antibacterial and anti-inflammatory activities both in vitro and in vivo. The anti-inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50-EFP that exert antibacterial and anti-inflammatory activities. PMID:27057196

  8. Anti-inflammatory activity of four Bolivian Baccharis species (Compositae).

    PubMed

    Abad, M J; Bessa, A L; Ballarin, B; Aragón, O; Gonzales, E; Bermejo, P

    2006-02-20

    Hexanic, dichloromethanic, ethanolic and aqueous extracts from Baccharis obtusifolia HBK, Baccharis latifolia (R. et P.) Pers., Baccharis pentlandii D.C. and Baccharis subulata Wedd., plants used in the traditional medicine of South America have been studied for their in vitro anti-inflammatory activity in cellular systems. Calcium ionophore A23187-stimulated mouse peritoneal macrophages were validated as a source of cyclooxygenase-1 (COX-1) (prostaglandin E2, PGE2) and 5-lipoxygenase (5-LOX) (leukotriene C4, LTC4), and mouse peritoneal macrophages stimulated with Escherichia coli lipopolysaccharide (LPS) were used for testing cyclooxygenase-2 (COX-2) (PGE2), nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) activity. Most of the extracts tested were active in all assays.

  9. [Specific inhibitors of cyclooxygenase-2 (COX-2): current knowledge and perspectives].

    PubMed

    Rioda, W T; Nervetti, A

    2001-01-01

    The Authors summarize the current knowledge on a new class of nonsteroidal anti-inflammatory drugs (NSAIDs), the coxib (celecoxib and rofecoxib), in the treatment of rheumatic diseases. Celecoxib and rofecoxib are selective cyclooxygenase-2 (COX-2) inhibitors which possess the same anti-inflammatory and analgesic activities, but a better gastric tolerability compared to the non-selective COX-1 and COX-2 inhibitors. The Authors also report other possible therapeutic effects of these NSADIs as evidenced by the more recent data of the literature. Celecoxib seems to reduce the incidence of new polyps in patients with familial adenomatous polyposis. It has been suggested the use of celecoxib as a protective drug against the development of colorectal cancer. Other (neoplastic) or pre-neoplastic conditions, such as bladder dysplasia, Barret esophagus, attinic keratosis and Alzheimer's disease seem to have benefit from this class of drugs.

  10. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors.

    PubMed

    Smith, Christina E; Soti, Subada; Jones, Torey A; Nakagawa, Akihisa; Xue, Ding; Yin, Hang

    2017-02-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity in both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design.

  11. In vivo and In vitro Anti-Inflammatory Activity of Indazole and Its Derivatives

    PubMed Central

    Muniappan, M.

    2016-01-01

    Introduction The inflammatory response is closely intertwined with the process of repair. However in some diseases the inflammatory response may be exaggerated and sustained without apparent benefit and even with severe adverse complications. For decades, we have been primarily relying upon Nonsteroidal (NSAID) and Steroidal Anti-Inflammatory agents for management of various inflammatory conditions. However, adverse effects of these drugs are severe which often leads to patient’s non-compliance with inadequate relief. Therefore, there has been a constant pursuit to develop newer anti - inflammatory treatment with fewer side effects. Aim The study was designed to investigate the possible anti- inflammatory activity of indazole, its derivatives and to further investigate the possible cellular mechanisms underlying the anti-inflammatory effect. Materials and Methods Carrageenan induced hind paw oedema in rats was employed to study the acute anti-inflammatory activity of indazole and its derivatives. Further, the role of cyclooxygenase – 2, pro-inflammatory cytokines like Tumour Necrosis Factor – α, Interleukin – 1β and free radical scavenging activity (LPO, DPPH and NO) in the action of indazole and its derivatives was investigated using in vitro assays. Results SPSS version 16.0 software was used for analyse the anti-inflamatory data. The IC50 values of indazole and its derivatives obtained in in vitro experiments were calculated by linear regression analysis. Indazole and its derivatives significantly, dose dependently and time dependently inhibited carrageenan induced hind paw oedema. In addition, the test compounds inhibited cyclooxygenase–2, pro-inflammatory cytokines and free radicals in a concentration dependent manner. Conclusion The results of the present study revealed the potential anti-inflammatory action of investigated indazoles. The inhibition of cyclooxygenase -2, cytokines and free radicals may contribute to the anti-inflammatory effect of

  12. Manassantin B isolated from Saururus chinensis inhibits cyclooxygenase-2-dependent prostaglandin D2 generation by blocking Fyn-mediated nuclear factor-kappaB and mitogen activated protein kinase pathways in bone marrow derived-mast cells.

    PubMed

    Lu, Yue; Hwang, Seung-Lark; Son, Jong Keun; Chang, Hyeun Wook

    2013-01-01

    The authors investigated the effect of manassantin B (Man B) isolated from Saururus chinensis (S. chinensis) on cyclooxygenase-2 (COX-2)-dependent prostaglandin D2 (PGD2) generation in mouse bone marrow derived-mast cells (BMMCs). Man B inhibited the generation of PGD2 dose-dependently by inhibiting COX-2 expression in immunoglobulin E (IgE)/Ag-stimulated BMMCs. To elucidate the mechanism responsible for the inhibition of COX-2 expression by Man B, the effects of Man B on the activation of nuclear factor-kappaB (NF-κB), a transcription factor essential and mitogen-activated protein kinases (MAPKs) for COX-2 induction, were examined. Man B attenuated the nuclear translocation of NF-κB p65 and its DNA-binding activity by inhibiting inhibitors of kappa Bα (IκBα) degradation and concomitantly suppressing IκB kinase (IKK) phosphorylation. In addition, Man B suppressed phosphorylation of MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38. It was also found that Man B suppressed Fyn kinase activation and consequent downstream signaling processes, including those involving Syk, Gab2, and Akt. Taken together, the present results suggest that Man B suppresses COX-2 dependent PGD2 generation by primarily inhibiting Fyn kinase in FcεRI-mediated mast cells.

  13. Anti-Inflammatory Effects of Hyptis albida Chloroform Extract on Lipopolysaccharide-Stimulated Peritoneal Macrophages

    PubMed Central

    Sánchez Miranda, Elizabeth; Pérez Ramos, Julia; Fresán Orozco, Cristina; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

    2013-01-01

    We examined the effects of a chloroform extract of Hyptis albida (CHA) on inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal macrophages. Our findings indicate that CHA inhibits LPS-induced production of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). During the process, levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric oxide (NO) increased in the mouse peritoneal macrophages; however, the extract suppressed them significantly. These results provide novel insights into the anti-inflammatory actions of CHA and support its potential use in the treatment of inflammatory diseases. PMID:23970974

  14. Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice

    PubMed Central

    Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang

    2015-01-01

    Abstract In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases. PMID:25494361

  15. Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy

    PubMed Central

    Mitchell, Jane A; Warner, Timothy D

    1999-01-01

    Cyclo-oxygenase is expressed in cells in two distinct isoforms. Cyclo-oxygenase-1 is present constitutively whilst cyclo-oxygenase-2 is expressed primarily after inflammatory insult. The activity of cyclo-oxygenase-1 and -2 results in the production of a variety of potent biological mediators (the prostaglandins) that regulate homeostatic and disease processes. Inhibitors of cyclo-oxygenase include the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, ibuprofen and diclofenac. NSAIDs inhibit cyclo-oxygenase-2 at the site of inflammation, to produce their therapeutic benefits, as well as cyclo-oxygenase-1 in the gastric mucosa, which produces gastric damage. Most recently selective inhibitors of cyclo-oxygenase-2 have been developed and introduced to man for the treatment of arthritis. Moreover, recent epidemiological evidence suggests that cyclo-oxygenase inhibitors may have important therapeutic relevance in the prevention of some cancers or even Alzheimer's disease. This review will discuss how the new advancements in NSAIDs research has led to the development of a new class of NSAIDs that has far reaching implications for the treatment of disease. PMID:10578123

  16. Anti-Inflammatory and Antiarthritic Activity of Anthraquinone Derivatives in Rodents

    PubMed Central

    Kshirsagar, Ajay D.; Panchal, Prashant V.; Harle, Uday N.; Nanda, Rabindra K.; Shaikh, Haidarali M.

    2014-01-01

    Aloe emodin is isolated compound of aloe vera which is used traditionally as an anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl or sulfated forms of aloe emodin may provide some limitations in its absorption capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO) and prostaglandin E2, via its action on murine macrophages. However, present work evidenced that molecular docking of aloe emodin modulates the anti-inflammatory activity, as well as expression of COX-2 (cyclooxygenase-2) in rodent. The AEC (4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2 carboxylic acid) was synthesized using aloe emodin as starting material. The study was planned for evaluation of possible anti-inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and complete Freund's adjuvant induced arthritis in rats. The AE (aloe emodin) and AEC significantly (P < 0.001) reduced carrageenan induced paw edema at 50 and 75 mg/kg. Complete Freund's adjuvant induced arthritis model showed significant (P < 0.001) decrease in injected and noninjected paw volume, arthritic score. AE and AEC showed significant effect on various biochemical, antioxidant, and hematological parameters. Diclofenac sodium 10 mg/kg showed significant (P < 0.001) inhibition in inflammation and arthritis. PMID:25610704

  17. Molecular mechanism of protopanaxadiol saponin fraction-mediated anti-inflammatory actions

    PubMed Central

    Yang, Yanyan; Lee, Jongsung; Rhee, Man Hee; Yu, Tao; Baek, Kwang-Soo; Sung, Nak Yoon; Kim, Yong; Yoon, Keejung; Kim, Ji Hye; Kwak, Yi-Seong; Hong, Sungyoul; Kim, Jong-Hoon; Cho, Jae Youl

    2014-01-01

    Background Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity. Methods We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. Results PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α, and prostaglandin E2], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels. Conclusion These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3). PMID:25535478

  18. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

    PubMed Central

    Shahbazi, Sajad; Sahrawat, Tammanna R.; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

  19. Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

    PubMed Central

    de Morais Lima, Gedson Rodrigues; Machado, Flavia Danniele Frota; Périco, Larissa Lucena; de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Souza Brito, Alba Regina Monteiro; Pellizzon, Cláudia Helena; Hiruma-Lima, Clélia Akiko; Tavares, Josean Fechine; Barbosa Filho, José Maria; Batista, Leônia Maria

    2017-01-01

    AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease. PMID:28293082

  20. Anti-Inflammatory and Anti-Superbacterial Properties of Sulforaphane from Shepherd's Purse

    PubMed Central

    Choi, Woo Jin; Kim, Seong Keun; Park, Hee Kuk; Sohn, Uy Dong

    2014-01-01

    Shepherd's purse, Capsella bursa-pastoris (L.) Medik., has been considered a health food for centuries in Asia and is known to contain the isothiocyanate compound sulforaphane. In this study, we evaluated the anti-inflammatory and antibacterial properties of a sulforaphane-containing solution (SCS) isolated from shepherd's purse. SCS had significant anti-inflammatory activity indicated by the decreased levels of nitric oxide (NO), cytokines (interleukin 1β [IL-1β], IL-6, and IL-10), and prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. In addition, SCS decreased the inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) levels, which confirmed the anti-inflammatory activity of SCS. Further, SCS inhibited vancomycin-resistant enterococci (VRE) and Bacillus anthracis. The minimal inhibitory concentration was 250 µg/ml for VRE and 1,000 µg/ml for B. anthracis. Taken together, these data indicate that SCS has potential anti-inflammatory and anti-superbacterial properties, and thus it can be used as a functional food or pharmaceutical. PMID:24634594

  1. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    PubMed Central

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  2. Anti-inflammatory principles from the fruits of Evodia rutaecarpa and their cellular action mechanisms.

    PubMed

    Choi, Yong Hwan; Shin, Eun Myoung; Kim, Yeong Shik; Cai, Xing Fu; Lee, Jung Joon; Kim, Hyun Pyo

    2006-04-01

    The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin E2 synthesis from lipopolysaccharide-treated RAW 264.7 cells at 1-10 microM. Evodiamine inhibited cyclooxygenase-2 induction and NF-kappaB activation, while rutaecarpine did not. On the other hand, goshuyuamide II inhibited 5-lipoxygenase from RBL-1 cells (IC50 = 6.6 microM), resulting in the reduced synthesis of leukotrienes. However, these three compounds were not inhibitory against inducible nitric oxide synthase-mediated nitric oxide production from RAW cells up to 50 micorM. These pharmacological properties may provide the additional scientific rationale for anti-inflammatory use of the fruits of E. rutaecarpa.

  3. Lactic Acid Fermentation of Cactus Cladodes (Opuntia ficus-indica L.) Generates Flavonoid Derivatives with Antioxidant and Anti-Inflammatory Properties.

    PubMed

    Filannino, Pasquale; Cavoski, Ivana; Thlien, Nadia; Vincentini, Olimpia; De Angelis, Maria; Silano, Marco; Gobbetti, Marco; Di Cagno, Raffaella

    2016-01-01

    Cactus pear (Opuntia ficus-indica L.) is widely distributed in the arid and semi-arid regions throughout the world. In the last decades, the interest towards vegetative crop increased, and cladodes are exploited for nutraceutical and health-promoting properties. This study aimed at investigating the capacity of selected lactic acid bacteria to increase the antioxidant and anti-inflammatory properties of cactus cladodes pulp, with the perspective of producing a functional ingredient, dietary supplement or pharmaceutical preparation. Preliminarily, the antioxidant activity was determined through in vitro assays. Further, it was confirmed through ex vivo analysis on intestinal Caco-2/TC7 cells, and the profile of flavonoids was characterized. Cactus cladode pulp was fermented with lactic acid bacteria, which were previously selected from plant materials. Chemically acidified suspension, without bacterial inoculum and incubated under the same conditions, was used as the control. Lactobacillus plantarum CIL6, POM1 and 1MR20, Lactobacillus brevis POM2 and POM4, Lactobacillus rossiae 2LC8 and Pediococcus pentosaceus CILSWE5 were the best growing strains. Fermentation of cladode pulp with L. brevis POM2 and POM4 allowed the highest concentration of γ-amino butyric acid. Lactic acid fermentation had preservative effects (P<0.05) on the levels of vitamin C and carotenoids. Two flavonoid derivatives (kaemferol and isorhamnetin) were identified in the ethyl acetate extracts, which were considered to be the major compounds responsible for the increased radical scavenging activity. After inducing oxidative stress by IL-1β, the increased antioxidant activity (P<0.05) of fermented cladode pulp was confirmed using Caco-2/TC7 cells. Fermented cladode pulp had also immune-modulatory effects towards Caco-2 cells. Compared to the control, fermented cladode pulp exhibited a significantly (P<0.05) higher inhibition of IL-8, TNFα and prostaglandins PGE2 synthesis. The highest

  4. Lactic Acid Fermentation of Cactus Cladodes (Opuntia ficus-indica L.) Generates Flavonoid Derivatives with Antioxidant and Anti-Inflammatory Properties

    PubMed Central

    Filannino, Pasquale; Cavoski, Ivana; Thlien, Nadia; Vincentini, Olimpia; De Angelis, Maria; Silano, Marco; Gobbetti, Marco; Di Cagno, Raffaella

    2016-01-01

    Cactus pear (Opuntia ficus-indica L.) is widely distributed in the arid and semi-arid regions throughout the world. In the last decades, the interest towards vegetative crop increased, and cladodes are exploited for nutraceutical and health-promoting properties. This study aimed at investigating the capacity of selected lactic acid bacteria to increase the antioxidant and anti-inflammatory properties of cactus cladodes pulp, with the perspective of producing a functional ingredient, dietary supplement or pharmaceutical preparation. Preliminarily, the antioxidant activity was determined through in vitro assays. Further, it was confirmed through ex vivo analysis on intestinal Caco-2/TC7 cells, and the profile of flavonoids was characterized. Cactus cladode pulp was fermented with lactic acid bacteria, which were previously selected from plant materials. Chemically acidified suspension, without bacterial inoculum and incubated under the same conditions, was used as the control. Lactobacillus plantarum CIL6, POM1 and 1MR20, Lactobacillus brevis POM2 and POM4, Lactobacillus rossiae 2LC8 and Pediococcus pentosaceus CILSWE5 were the best growing strains. Fermentation of cladode pulp with L. brevis POM2 and POM4 allowed the highest concentration of γ-amino butyric acid. Lactic acid fermentation had preservative effects (P<0.05) on the levels of vitamin C and carotenoids. Two flavonoid derivatives (kaemferol and isorhamnetin) were identified in the ethyl acetate extracts, which were considered to be the major compounds responsible for the increased radical scavenging activity. After inducing oxidative stress by IL-1β, the increased antioxidant activity (P<0.05) of fermented cladode pulp was confirmed using Caco-2/TC7 cells. Fermented cladode pulp had also immune-modulatory effects towards Caco-2 cells. Compared to the control, fermented cladode pulp exhibited a significantly (P<0.05) higher inhibition of IL-8, TNFα and prostaglandins PGE2 synthesis. The highest

  5. Ginger--an herbal medicinal product with broad anti-inflammatory actions.

    PubMed

    Grzanna, Reinhard; Lindmark, Lars; Frondoza, Carmelita G

    2005-01-01

    The anti-inflammatory properties of ginger have been known and valued for centuries. During the past 25 years, many laboratories have provided scientific support for the long-held belief that ginger contains constituents with antiinflammatory properties. The original discovery of ginger's inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. The characterization of the pharmacological properties of ginger entered a new phase with the discovery that a ginger extract (EV.EXT.77) derived from Zingiber officinale (family Zingiberaceae) and Alpina galanga (family Zingiberaceae) inhibits the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2. This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. Identification of the molecular targets of individual ginger constituents provides an opportunity to optimize and standardize ginger products with respect to their effects on specific biomarkers of inflammation. Such preparations will be useful for studies in experimental animals and humans.

  6. Anti-inflammatory effects of enzymatic hydrolysates of velvet antler in RAW 264.7 cells in vitro and zebrafish model

    PubMed Central

    Lee, Seung-Hong; Yang, Hye-Won; Ding, Yuling; Wang, Yanmei; Jeon, You-Jin; Moon, Sang-Ho; Jeon, Byong-Tae; Sung, Si-Heung

    2015-01-01

    Enzymatic hydrolysis has been successfully used for the extraction of numerous biologically active components from a wide variety of natural sources. In the present study, velvet antler was subjected to the extraction process using Alcalase protease. We analyzed bioactive components, such as uronic acid, sulfated-glycosaminoglycans (sulfated-GAGs), and sialic acid, present in the velvet antler Alcalase hydrolysate (VAAH) and assessed their anti-inflammatory effects in zebrafish as well as in vitro using cell lines. VAAH mainly contained uronic acid (78.22 mg/g) and sulfated-GAGs (50.47 mg/g), while the amount of sialic acid was negligible (5.55 mg/g). VAAH inhibited the production of nitric oxide (NO) by lipopolysaccharide (LPS)-induced cells in a dose-dependent manner and the inhibitory effect of VAAH on NO production was higher than that of hot water extracts. VAAH treatment also reduced the expression of inflammatory mediators such as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, we evaluated anti-inflammatory effects of VAAH using LPS-stimulated zebrafish. Treatment with LPS significantly increased cell death, NO, and reactive oxygen species (ROS) levels in zebrafish. Notably, VAAH significantly inhibited the extent of LPS-stimulated cell death and generation of NO and ROS in zebrafish. These results suggest that VAAH alleviated inflammation and cell death by inhibiting the generation of ROS induced by LPS treatment. Thus, VAAH could be used as a potential natural remedy with a strong anti-inflammatory effect. Taken together, we believe that based on our present results, enzymatic hydrolysis of velvet antler may be an effective process to make antler products acceptable as elements of health foods and nutraceutical components with increased biological activity. PMID:27152107

  7. XH-14, a novel danshen methoxybenzo[b]furan derivative, exhibits anti-inflammatory properties in lipopolysaccharide-treated RAW 264.7 cells

    PubMed Central

    2013-01-01

    Background XH-14 isolated from Salvia miltiorrhiza is a bioactive component and adenosine antagonist. In the present study, we evaluated anti-inflammatory properties of XH-14 in murine macrophages. Methods RAW 264.7 murine macrophage cell line was cultured with various concentrations of XH-14 in the absence or presence of lipopolysaccharide (LPS). LPS-induced release and mRNA expression of inflammatory mediators were examined by ELISA and real-time PCR. The modification of signal pathways involved in inflammatory reactions was determined by Western blotting analysis. Results XH-14 suppressed the generation of nitric oxide (NO) and prostaglandin E2, and the expression of inducible NO synthase and cyclooxygenase-2 induced by LPS. Similarly, XH-14 inhibited the release of pro-inflammatory cytokines induced by LPS in RAW 264.7 cells. The underlying mechanism of XH-14 on anti-inflammatory action was correlated with down-regulation of mitogen-activated protein kinase and activator protein-1 activation. Conclusions XH-14 inhibits the production of several inflammatory mediators and so might be useful for the treatment of various inflammatory diseases. PMID:23305138

  8. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  9. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    SciTech Connect

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  10. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate

    PubMed Central

    du Souich, Patrick; García, Antonio G; Vergés, Josep; Montell, Eulàlia

    2009-01-01

    Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1–3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 p (IL-1p)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-KB (NF-kB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1 p and TNF-a, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-κB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases. PMID:19522843

  11. Modification of palm oil for anti-inflammatory nutraceutical properties.

    PubMed

    Zainal, Zaida; Longman, Andrea J; Hurst, Samantha; Duggan, Katrina; Hughes, Clare E; Caterson, Bruce; Harwood, John L

    2009-07-01

    Palm oil is one of the most important edible oils in the world. Its composition (rich in palmitate and oleate) make it suitable for general food uses but its utility could be increased if its fatty acid quality could be varied. In this study, we have modified a palm olein fraction by transesterification with the n-3 polyunsaturated fatty acids, alpha-linolenate or eicosapentaenoic acid (EPA). Evaluation of the potential nutritional efficacy of the oils was made using chondrocyte culture systems which can be used to mimic many of the degenerative and inflammatory pathways involved in arthritis. On stimulation of such cultures with interleukin-1alpha, they showed increased expression of cyclooxygenase-2, the inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-1alpha and IL-1beta and the proteinase ADAMTS-4. This increased expression was not affected by challenge of the cultures with palm olein alone but showed concentration-dependent reduction by the modified oil in a manner similar to EPA. These results show clearly that it is possible to modify palm oil conveniently to produce a nutraceutical with effective anti-inflammatory properties.

  12. 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

  13. Constituents from Vigna vexillata and Their Anti-Inflammatory Activity

    PubMed Central

    Leu, Yann-Lii; Hwang, Tsong-Long; Kuo, Ping-Chung; Liou, Kun-Pei; Huang, Bow-Shin; Chen, Guo-Feng

    2012-01-01

    The seeds of Vigna genus are important food resources and there have already been many reports regarding their bioactivities. In our preliminary bioassay, the chloroform layer of methanol extracts of V. vexillata demonstrated significant anti-inflammatory bioactivity. Therefore, the present research is aimed to purify and identify the anti-inflammatory principles of V. vexillata. One new sterol (1) and two new isoflavones (2,3) were reported from the natural sources for the first time and their chemical structures were determined by the spectroscopic and mass spectrometric analyses. In addition, 37 known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. Among the isolates, daidzein (23), abscisic acid (25), and quercetin (40) displayed the most significant inhibition of superoxide anion generation and elastase release. PMID:22949828

  14. Anti-inflammatory activity of fisetin in human gingival fibroblasts treated with lipopolysaccharide.

    PubMed

    Gutiérrez-Venegas, Gloria; Contreras-Sánchez, Anabel; Ventura-Arroyo, Jairo Agustín

    2014-10-01

    Fisetin is an anti-inflammatory flavonoid; however, its anti-inflammatory mechanism is not yet understood. In this study, we evaluated the anti-inflammatory effect of fisetin and its association with mitogen-activated protein kinase (MAPK) and nuclear factor kappa-beta pathways in human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) obtained from Porphyromonas gingivalis. The cell signaling, cell viability, and cyclooxygenase-2 (COX-2) expression of HGFs treated with various concentrations (0, 1, 5, 10, and 15 μM) of fisetin were measured by cell viability assay (MTT), Western blotting, and reverse transcriptase polymerase chain reaction analysis on COX-2. We found that fisetin significantly reduced the synthesis and expression of prostaglandin E2 in HGFs treated with LPS. Activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK was suppressed consistently by fisetin in HGFs treated with LPS. The data indicate that fisetin inhibits MAPK activation and COX-2 expression without affecting cell viability. These findings may be valuable for understanding the mechanism of the effect of fisetin on periodontal disease.

  15. Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation.

    PubMed

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender; Raj, Arun

    2016-11-01

    Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine. The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions. In the present study, we sought to investigate the anti-inflammatory activity of P. kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats. In addition, its immunomodulatory activity was evaluated in Complete Freund's Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Pretreatment with P. kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner. This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages. Additionally, P. kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freund's Adjuvant-induced activated peritoneal macrophages. Furthermore, P. kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW264.7 macrophages. Taken together, these results suggest that P. kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling.

  16. Anti-inflammatory effect of supercritical extract and its constituents from Ishige okamurae

    PubMed Central

    Ko, Eun-Yi; Yoon, Weon-Jong; Lee, Hae-Won; Heo, Soo-Jin; Ko, Young-Hwan; Fernando, I.P. Shanura; Cho, Kichul; Lee, Chi-Heon; Hur, Sung-Pyo; Cho, Su-Hyeon; Ahn, Ginnae; Kim, Daekyung; Kim, Kil-Nam

    2016-01-01

    The anti-inflammatory properties of the supercritical fluid extract of Ishige okamurae (SFEIO) on lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. The lipid profile of the SFEIO, reviled the presence of palmitic acid (220.2 mg/g), linoleic acid (168.0 mg/g), and oleic acid (123.0 mg/g). SFEIO was found to exert it's anti-inflammatory effects through inhibiting nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 production in LPS-stimulated RAW 264.7 cells, without inducing cytotoxicity. SFEIO did not effect on the LPS-induced p38 kinase phosphorylation, whereas it attenuated the extracellular-related signaling kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation. Furthermore, SFEIO inhibited the LPS-induced IκB-α degradation and p50 NF-κB activation. These results suggest that SFEIO exerts its anti-inflammatory effects in LPS-activated RAW 264.7 cells by down-regulating the activation of ERK, JNK, and NF-κB. PMID:27822172

  17. Evaluation of Anti-Inflammatory Properties of Isoorientin Isolated from Tubers of Pueraria tuberosa

    PubMed Central

    Anilkumar, Kotha; Reddy, Gorla V.; Azad, Rajaram; Yarla, Nagendra Sastry; Dharmapuri, Gangappa; Srivastava, Anand

    2017-01-01

    Inflammation is the major causative factor of different diseases such as cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, and cancer. Anti-inflammatory drugs are often the first step of treatment in many of these diseases. The present study is aimed at evaluating the anti-inflammatory properties of isoorientin, a selective cyclooxygenase-2 (COX-2) inhibitor isolated from the tubers of Pueraria tuberosa, in vitro on mouse macrophage cell line (RAW 264.7) and in vivo on mouse paw edema and air pouch models of inflammation. Isoorientin reduced inflammation in RAW 264.7 cell line in vitro and carrageenan induced inflammatory animal model systems in vivo. Cellular infiltration into pouch tissue was reduced in isoorientin treated mice compared to carrageenan treated mice. Isoorientin treated RAW 264.7 cells and animals showed reduced expression of inflammatory proteins like COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 5-lipoxygenase (5-LOX), and interleukin 1-β (IL-1-β) both in vitro and in vivo. The antioxidant enzyme levels of catalase and GST were markedly increased in isoorientin treated mice compared to carrageenan treated mice. These results suggest that isoorientin, a selective inhibitor of COX-2, not only exerts anti-inflammatory effects in LPS induced RAW cells and carrageenan induced inflammatory model systems but also exhibits potent antioxidant properties. PMID:28243356

  18. In vivo and in vitro anti-inflammatory effects of a novel derivative of icariin.

    PubMed

    Wu, Jinfeng; Du, Juan; Xu, Changqing; Le, Jingjing; Liu, Baojun; Xu, Yizhe; Dong, Jingcheng

    2011-03-01

    Icariin is the major active constituent of Epimedii Herba. Our recent study showed that icariin displayed anti-inflammatory potential. One novel derivate of icariin is 3,5,7-Trihydroxy-4'-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone (ICT). Little is known about ICT's pharmacological activities. In our study, the anti-inflammatory properties of ICT were evaluated. Murine RAW264.7 cells and C57BL/6J mice stimulated by lipopolysaccharide (LPS) was used as in vitro and in vivo inflammatory model, respectively. Our data showed that ICT (1-100 μg/mL) significantly inhibited LPS-induced tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2) production in vitro. These effects did not depend on cytotoxicity. The in vivo assay displayed that pretreatment of C57BL/6J mice with ICT (25-100 mg/kg, by gavage) for 3 days decreased LPS-induced serum levels of TNF-α, PGE2, and neutrophils CD11b expression dose-dependently. Furthermore, our data suggested that ICT reduced NO and PGE2 levels by inhibiting inducible NO synthase and cyclooxygenase-2 protein expression. To our knowledge, it is the first time that the anti-inflammatory effects of ICT have been evaluated.

  19. Chemical composition and anti-inflammatory effects of essential oil from Hallabong flower

    PubMed Central

    Kim, Min-Jin; Yang, Kyong-Wol; Kim, Sang Suk; Park, Suk Man; Park, Kyung Jin; Kim, Kwang Sik; Choi, Young Hun; Cho, Kwang Keun; Lee, Nam Ho; Hyun, Chang-Gu

    2013-01-01

    A number of essential oils derived from plants are claimed to have several medicinal functions, including anti-cancer and anti-inflammation effects. However, the chemical composition and biological activities of flower-derived components have not been sufficiently characterized. Therefore, we investigated the composition of essential oils from Hallabong flower [(Citrus unshiu Marcov × Citrus sinensis Osbeck) × Citrus reticulata Blanco] and their anti-inflammatory effects. Hydro-distilled essential oils (HEOs) were analyzed using gas chromatography-mass spectrometry (GC-MS). In total, 21 components were identified, representing more than 98 % of the oils, with sabinene (34.75 %), linalool (14.77 %), β-ocimene (11.07 %), 4-terpineol (9.63 %), l-limonene (5.88 %), and γ-terpinene (4.67 %) as the main components. In the present study, we also investigated the anti-inflammatory effects of HEOs on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. HEOs were found to inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production and to suppress the LPS-induced expression of cyclooxygenase-2 (COX-2) protein. In addition, HEOs downregulated the production of the inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β (IC50 values are 0.05 %, 0.02 %, and 0.01 %, respectively). On the basis of these results, we suggest that HEOs can be considered potential anti-inflammatory candidates for therapeutic use in humans. PMID:27366141

  20. ANTI-INFLAMMATORY ACTIVITY OF DODONAEA VISCOSE

    PubMed Central

    Mahadevan, N.; Venkatesh, Sama; Suresh, B.

    1998-01-01

    Dodonaea viscose, Linn is a widely grown plant of Nilgiris district of Tamil and is commonly used by the tribals of Nilgiris as a traditional medicine for done fracture and joint sprains. Since it is generally believed tat fractures are accompanied by either some degree of injury or inflammations, it was felt desirable to carry our anti inflammatory activity of Dodonaea viscose. Anti-inflammatory activity of the plant was carried out by carrageenin induced paw edema method in Wister albino rats. PMID:22556883

  1. A Revised Mechanism for Human Cyclooxygenase-2*

    PubMed Central

    Liu, Yi; Roth, Justine P.

    2016-01-01

    The mechanism of ω-6 polyunsaturated fatty acid oxidation by wild-type cyclooxygenase 2 and the Y334F variant, lacking a conserved hydrogen bond to the catalytic tyrosyl radical/tyrosine, was examined for the first time under physiologically relevant conditions. The enzymes show apparent bimolecular rate constants and deuterium kinetic isotope effects that increase in proportion to co-substrate concentrations before converging to limiting values. The trends exclude multiple dioxygenase mechanisms as well as the proposal that initial hydrogen atom abstraction from the fatty acid is the first irreversible step in catalysis. Temperature dependent kinetic studies reinforce the novel finding that hydrogen transfer from the reduced catalytic tyrosine to a terminal peroxyl radical is the first irreversible step that controls regio- and stereospecific product formation. PMID:26565028

  2. Anti-inflammatory activity of mycelial extracts from medicinal mushrooms.

    PubMed

    Geng, Yan; Zhu, Shuiling; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Zheng-Hong

    2014-01-01

    Medicinal mushrooms have been essential components of traditional Chinese herbal medicines for thousands of years, and they protect against diverse health-related conditions. The components responsible for their anti-inflammatory activity have yet to be fully studied. This study investigates the anti-inflammatory activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia in submerged culture from 5 commercially available medicinal mushrooms, namely Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. MTT colorimetric assay was applied to measure the cytotoxic effects of different extracts. Their anti-inflammatory activities were evaluated via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in murine macrophage-like cell line RAW264.7 cells. Of the 20 extracts, n-hexane, chloroform, ethyl acetate, and methanol extracts from C. sinensis, C. mortierella, and G. lucidum; chloroform extracts from H. erinaceus and A. mellea; and ethyl acetate extracts from A. mellea at nontoxic concentrations (<300 μg/mL) dose-dependently inhibited LPS-induced NO production. Among them, the chloroform extract from G. lucidum was the most effective inhibitor, with the lowest half maximal inhibitory concentration (64.09 ± 6.29 μg/mL) of the LPS-induced NO production. These results indicate that extracts from medicinal mushrooms exhibited anti-inflammatory activity that might be attributable to the inhibition of NO generation and can therefore be considered a useful therapeutic and preventive approach to various inflammation-related diseases.

  3. Cyclooxygenase-2 inhibitors: promise or peril?

    PubMed Central

    Mengle-Gaw, Laurel J; Schwartz, Benjamin D

    2002-01-01

    The discovery of two isoforms of the cyclooxygenase enzyme, COX-1 and COX-2, and the development of COX-2-specific inhibitors as anti-inflammatories and analgesics have offered great promise that the therapeutic benefits of NSAIDs could be optimized through inhibition of COX-2, while minimizing their adverse side effect profile associated with inhibition of COX-1. While COX-2 specific inhibitors have proven to be efficacious in a variety of inflammatory conditions, exposure of large numbers of patients to these drugs in postmarketing studies have uncovered potential safety concerns that raise questions about the benefit/risk ratio of COX-2-specific NSAIDs compared to conventional NSAIDs. This article reviews the efficacy and safety profiles of COX-2-specific inhibitors, comparing them with conventional NSDAIDs. PMID:12467519

  4. Tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in RAW264.7 macrophages.

    PubMed

    Yam, Mun-Li; Abdul Hafid, Sitti Rahma; Cheng, Hwee-Ming; Nesaretnam, Kalanithi

    2009-09-01

    Tocotrienols are powerful chain breaking antioxidant. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions. This study was undertaken to investigate the anti-inflammatory effects of tocotrienol-rich fraction (TRF) and individual tocotrienol isoforms namely delta-, gamma-, and alpha-tocotrienol on lipopolysaccharide-stimulated RAW264.7 macrophages. The widely studied vitamin E form, alpha-tocopherol, was used as comparison. Stimulation of RAW264.7 with lipopolysaccharide induced the release of various inflammatory markers. 10 mcirog/ml of TRF and all tocotrienol isoforms significantly inhibited the production of interleukin-6 and nitric oxide. However, only alpha-tocotrienol demonstrated a significant effect in lowering tumor necrosis factor-alpha production. Besides, TRF and all tocotrienol isoforms except gamma-tocotrienol reduced prostaglandin E(2) release. It was accompanied by the down-regulation of cyclooxygenase-2 gene expression by all vitamin E forms except alpha-tocopherol. Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than alpha-tocopherol and the most effective form is delta-tocotrienol.

  5. Effects of a cyclooxygenase-2 preferential inhibitor in young healthy dogs exposed to air pollution: a pilot study.

    PubMed

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Gómez-Garza, Gilberto; Carrasco-Portugal, Miriam Del C; Pérez-Guillé, Beatriz; Flores-Murrieta, Francisco J; Pérez-Guillé, Gabriela; Osnaya, Norma; Juárez-Olguín, Hugo; Monroy, Maria E; Monroy, Silvia; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Patel, Sarjubhai A; Kumarathasan, Prem; Vincent, Renaud; Henríquez-Roldán, Carlos; Torres-Jardón, Ricardo; Maronpot, Robert R

    2009-08-01

    Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs. Nimesulide significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1beta (p = .03), and heart IL1beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Abeta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.

  6. Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent.

    PubMed

    Nikhil, Kumar; Sharan, Shruti; Palla, Srinivasa Rao; Sondhi, Sham M; Peddinti, Rama Krishna; Roy, Partha

    2015-09-01

    Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent.

  7. Anti-inflammatory activity studies on the stems and roots of Jasminum lanceolarium Roxb.

    PubMed

    Yan, Wen-xia; Zhang, Jian-hua; Zhang, Yi; Meng, Da-li; Yan, Dan

    2015-08-02

    Jasminum lanceolarium Roxb is an important traditional Chinese medicine. Its stems and roots have been used for the treatment of rheumatism and fever while the leaves are used as an anti-inflammatory agent to relieve pain. In order to support its traditional Chinese medicinal uses, five animal models were designed and the anti-inflammatory and analgesic properties of the 70% EtOH-H2O extracts of J. lanceolarium (EJL) were investigated. Meanwhile, biochemical parameters such as cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) in blood serum of rats exposed to acute (carrageenan) inflammation model were evaluated. At doses of 400 mg/kg, EJL exhibited higher anti-inflammation effect than that of indomethacin and better analgesic activity than that of aspirin (P<0.001). Furthermore, eleven isolated compounds including six lignanoids (1, 2, 6, 7, 8, and 11) and five iridoids (3, 4, 5, 9, and 10) were isolated from the active extracts and showed significant anti-inflammatory activities with the IC50 values of 1.76-5.22 mg/mL, respectively, when testing their inhibitory effects on phospholipase A2 in vitro. The results demonstrated that the possible anti-inflammatory mechanisms might be attributed to inhibit the hydrolysis of membrane phospholipids, production on both COX-2 and 5-LOX, and then finally inhibit the release of prostaglandins (PGs), which suggested that EJL had a non-selective inhibitory effect on the release or actions of these mediators, and might be a dual LOX-COX inhibitor for the treatment of inflammation from the natural resource. The studies on the animals and the inflammatory mediators, along with the bioactive compounds presumed that the existences of iridoids and lignanoids could be response for their bioactivities of the whole plants.

  8. Noni (Morinda citrifolia L.) Fruit Extracts Improve Colon Microflora and Exert Anti-Inflammatory Activities in Caco-2 Cells.

    PubMed

    Huang, Hsin-Lun; Liu, Cheng-Tzu; Chou, Ming-Chih; Ko, Chien-Hui; Wang, Chin-Kun

    2015-06-01

    Intestinal microflora and inflammation are associated with the risk of inflammatory bowel diseases. Noni (Morinda citrifolia L.) has various bioactivities, but its effect on colon health remains unknown. This study focused on the effects of fermented noni fruit extracts on colon microflora and inflammation of colon epithelial cells. The anti-inflammatory activities of ethanol and ethyl acetate extracts on Caco-2 cells were evaluated including interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). The growth of Lactobacillus and Bifidobacterium species was promoted by ethanol extract. Ethyl acetate extract decreased intracellular reactive oxygen species and significantly suppressed COX-2, IL-8, and prostaglandin E2 production and neutrophil chemotaxis by suppressing the translocation of the p65 subunit. Quercetin was the main contributor to the anti-inflammatory activity. The fermented noni fruit promoted probiotic growths and downregulated the intracellular oxidation and inflammation in Caco-2 cells. These results suggest that fermented noni fruit might protect against inflammatory diseases of the colon.

  9. Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Gopez, Jonas J.; Yue, Hongfei; Vasudevan, Ram; Malik, Amir S.; Fogelsanger, Lester N.; Lewis, Shawn; Panikashvili, David; Shohami, Esther; Jansen, Susan A.; Narayan, Raj K.; Strauss, Kenneth I.

    2006-01-01

    OBJECTIVE Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3–immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3–immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuro-protective endocannabinoid, in the injured brain. CONCLUSION These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials. PMID:15730585

  10. Anti-inflammatory activity of Chinese medicinal vine plants.

    PubMed

    Li, Rachel W; David Lin, G; Myers, Stephen P; Leach, David N

    2003-03-01

    Anti-inflammatory activities of ethanol extracts from nine vine plants used in traditional Chinese medicine to treat inflammatory conditions were evaluated against a panel of key enzymes relating to inflammation. The enzymes included cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), phospholipase A(2) (PLA(2)), 5-lipoxygenase (5-LO) and 12-lipoxygenase (12-LO). The vine plants studied were: the stem of Spatholobus suberectus Dunn, the stem of Trachelospermum jasminoides Lem., the root from Tripterygium wilfordii Hook. f., the stem of Sinomenium acutum Rehder and Wilson, the stem of Piper kadsura (Choisy) Ohwi, the stem of Polygonum multiflorum Thunb., the root and stem from Tinospora sagittata Gagnep., the root of Tinospora sinensis (Lour.) Merrill, and the stem of Clematis chinensis Osbeck. All of the plant extracts showed inhibitory activities against at least one of the enzymes in various percentages depending upon the concentrations. The extract from S. suberectus was found to be active against all enzymes except COX-2. Its IC(50) values were 158, 54, 31 and 35 microg/ml in COX-1, PLA(2), 5-LO and 12-LO assays, respectively. T. jasminoides showed potent inhibitory activities against both COX-1 (IC(50) 35 microg/ml) and PLA(2) (IC(50) 33 microg/ml). The most potent COX-1, COX-2 and 5-LO inhibition was observed in the extract of T. wilfordii with the IC(50) values of 27, 125 and 22 microg/ml, respectively. The findings of this study may partly explain the use of these vine plants in traditional Chinese medicine for the treatment of inflammatory conditions.

  11. Anti-inflammatory effect of geranium nanoemulsion macrophages induced with soluble protein of Candida albicans.

    PubMed

    Giongo, Janice Luehring; de Almeida Vaucher, Rodrigo; Sagrillo, Michele; Vianna Santos, Roberto Christ; Duarte, Marta M M F; Rech, Vírginia Cielo; Soares Lopes, Leonardo Quintana; Beatriz da Cruz, Ivana; Tatsch, Etiane; Moresco, Rafael Noal; Gomes, Patricia; Steppe, Martin

    2017-01-31

    Pelargonium graveolens is a member of the Geraniaceae family and has been used in folk medicine in many countries because of its anti-inflammatory activity. No studies have yet been reported to evaluate the anti-inflammatory activity of a nanoemulsion containing geranium oil (GO) model in macrophages. In this study the anti-inflammatory effect of Geranium nanoemulsion (NEG) macrophages induced with soluble proteins of Candida albicans was investigated. GO presented citronellol (17.74%) and geraniol (14.43%) as main constituents. The characterization in NEG was demonstrated, showing the particle size of 164 ± 3.5 nm, PDI of 0.12 ± 0.006 and zeta potential -10 mV ± 1.7. The MIC obtained for NEG and GO were 3.64 μg ml(-1) and 1.82 μg ml(-1), respectively. The viability of the macrophages treated with NEG and GO concentrations (1/2 x, 1x and 2x MIC) was evaluated. There was a significant reduction of viability and the MTT assay was not confirmed after the LDH assay. Anti-inflammatory activity was evaluated by determining nitric oxide (NO), cytokines (interleukin IL-1, IL-6 and IL-10), tumor necrosis factor-α (TNF) and the expression levels gene of interleukin (IL-2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The apoptosis inhibition capacity was assessed by determination of INFγ, caspase 3 and caspase 8. The results indicated that there was a significant increase of NO in the levels after treatment with NEG and significantly reduced levels after treatment with GO. The cytokines (IL-1, IL-6, IL-10, and TNF) were evaluated and NEG (½ x, 1x MIC) decreased IL-1 levels by 1.25-1.37 times, respectively. The NEG did not decrease IL-6 levels and a significant increase was observed for IL-10. GO significantly decreased IL-6 and IL-10 levels. There was a significant decrease in IL-2 and COX-2 levels and increased levels of iNOs. The levels of IFNγ and caspase-3 after treatment with NEG decreased indicating an anti-inflammatory

  12. The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist

    PubMed Central

    Su, Mingzhi; Cao, Jiafu; Huang, Jin; Liu, Sen; Im, Dong Soon; Yoo, Jin-Wook; Jung, Jee H.

    2017-01-01

    Previously, the authors found that 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) (a phthalimide analogue) bound to and activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Since PPAR-γ suppresses inflammatory responses, the present study was undertaken to investigate the anti-inflammatory effects of PD1. In lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, PD1 suppressed the inductions of pro-inflammatory factors, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Concomitantly, PD1 enhanced the expressions of anti-inflammatory factors, such as arginase-1 and interleukin-10 (IL-10), and suppressed LPS-evoked nuclear factor kappa B (NF-κB) p65 subunit phosphorylation in macrophages. In addition, PPAR-γ activated by PD1 was intensively translocated to the nucleus. These observations suggest that the anti-inflammatory mechanism of PD1 involves inhibition of the NF-κB pathway. In a subsequent in vivo animal experiment conducted using a carrageenan-induced acute inflammatory rat paw edema model, intraperitoneal injection of PD1 significantly reduced paw swelling. Histological analysis of rat paw tissue sections revealed less infiltration of immune cells in PD1-pretreated animals. These findings suggest that PD1 be viewed as a lead compound for the development of novel anti-inflammatory therapeutics. PMID:28054961

  13. ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action

    PubMed Central

    Lee, Jeong-Oog; Jeong, Deok; Kim, Mi-Yeon; Cho, Jae Youl

    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

  14. The Effect of Polyphenols Isolated from Cynanchi wilfordii Radix with Anti-inflammatory, Antioxidant, and Anti-bacterial Activity

    PubMed Central

    Jeong, Sunyoung; Lee, Sunwoo; Choi, Woo Jin; Sohn, Uy Dong

    2015-01-01

    Recently, Cynanchi wilfordii Radix has gained wide use in Asian countries as a functional food effective for relieving fatigue, osteoporosis, and constipation, particularly in menopausal disorders. However, its anti-inflammatory and anti-microbial activities have not been explored in detail to date. The anti-inflammatory, antioxidant, and anti-bacterial properties of the Cynanchi wilfordii Radix extracts obtained with water, methanol, ethanol, and acetone were compared. All 4 polyphenol-containing extracts exhibited anti-inflammatory and antioxidant effects. The ethanol extract was found to elicit the most potent reduction of nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine (IL-1β, IL-6, IL-10, and TNF-α) levels, as well as inhibit the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner. The evaluation of antioxidant activity also revealed the ethanol extract to have the highest free radical scavenging activity, measured as 85.3±0.4%, which is equivalent to 99.9% of the activity of α -tocopherol. In the assessment of anti-bacterial activity, only ethanol extract was found to inhibit the growth of the Bacillus species Bacillus cereus and Bacillus anthracis. These results show that polyphenols of Cynanchi wilfordii Radix have anti-inflammatory, antioxidant, and anti-bacterial properties that can be exploited and further improved for use as a supplementary functional food, in cosmetics, and for pharmaceutical purposes. PMID:25729277

  15. Enhanced anti-inflammatory potential of cinnamate-zinc layered hydroxide in lipopolysaccharide-stimulated RAW 264.7 macrophages

    PubMed Central

    Adewoyin, Malik; Mohsin, Sumaiyah Megat Nabil; Arulselvan, Palanisamy; Hussein, Mohd Zobir; Fakurazi, Sharida

    2015-01-01

    Background Cinnamic acid (CA) is a phytochemical originally derived from Cinnamomum cassia, a plant with numerous pharmacological properties. The intercalation of CA with a nanocarrier, zinc layered hydroxide, produces cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized. Intercalation is expected to improve the solubility and cell specificity of CA. The nanocarrier will also protect CA from degradation and sustain its release. The aim of this study was to assess the effect of intercalation on the anti-inflammatory capacity of CA. Methods In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined. Results Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only. Conclusion The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control. PMID:25995619

  16. Anti-inflammatory actions of acupuncture.

    PubMed Central

    Zijlstra, Freek J; van den Berg-de Lange, Ineke; Huygen, Frank J P M; Klein, Jan

    2003-01-01

    Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of beta-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-alpha and interleukin-10 are discussed. PMID:12775355

  17. Anti-Inflammatory Effect of Selected Dihydroxyflavones

    PubMed Central

    Sangeetha, K.S.Sridevi

    2015-01-01

    Background The mechanism of inflammation is attributed, to release of reactive oxygen species from activated neutrophils and macrophages. Over production of reactive oxygen species may result in tissue injury by damaging macromolecules. Flavones are the polyphenolic compounds with antioxidant property. This antioxidant property of flavones may have beneficial effect against inflammation. Aim To study the anti-inflammatory effect of selected dihydroxyflavones (DHF) in albino rats. The prime objective of the present study is to identify safe and effective agents to treat inflammation from among the selected DHF group of compounds. Materials and Methods The present study was designed to investigate the anti-inflammatory action of four selected dihydroxyflavone derivatives; 2’,3’- dihydroxyflavone and 2’, 4’ -dihydroxyflavones, 5, 3’- dihydroxyflavone and 7, 3’ dihydroxyflavone. The anti-inflammatory activity of selected DHF was studied in rats by carrageenan induced hind paw oedema method. Results All the selected dihydroxyflavone derivatives showed dose and time dependent inhibition of carrageenan induced paw oedema. PMID:26155493

  18. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard.

    PubMed

    Chang, Yoke-Chen; Wang, James D; Hahn, Rita A; Gordon, Marion K; Joseph, Laurie B; Heck, Diane E; Heindel, Ned D; Young, Sherri C; Sinko, Patrick J; Casillas, Robert P; Laskin, Jeffrey D; Laskin, Debra L; Gerecke, Donald R

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal-epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure.

  19. Therapeutic Potential of a Non-Steroidal Bifunctional Anti-Inflammatory and Anti-Cholinergic Agent against Skin Injury Induced by Sulfur Mustard

    PubMed Central

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.

    2014-01-01

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 hr post-SM exposure. After 96 hr, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermalepidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. PMID:25127551

  20. Anti-inflammatory activity of polyphenolics from açai (Euterpe oleracea Martius) in intestinal myofibroblasts CCD-18Co cells.

    PubMed

    Dias, Manoela Maciel dos Santos; Martino, Hércia Stampini Duarte; Noratto, Giuliana; Roque-Andrade, Andrea; Stringheta, Paulo César; Talcott, Stephen; Ramos, Afonso Mota; Mertens-Talcott, Susanne U

    2015-10-01

    The demand for tropical fruits high in polyphenolics including açai (Euterpe oleracea Mart.) has been increasing based on ascribed health benefits and antioxidant properties. This study evaluated the anti-inflammatory activities of açai polyphenolics in human colon myofibroblastic CCD-18Co cells to investigate the suppression of reactive oxygen species (ROS), and mRNA and protein expression of inflammatory proteins. Non-cytotoxic concentrations of açai extract, 1-5 mg gallic acid equivalent L(-1), were selected. The generation of ROS was induced by lipopolysaccharide (LPS) and açai extract partially reversed this effect to 0.53-fold of the LPS-control. Açai extract (5 mg GAE L(-1)) down-regulated LPS-induced mRNA-expression of tumor necrosis factor alpha, TNF-α (to 0.42-fold), cyclooxygenase 2, COX-2 (to 0.61-fold), toll-like receptor-4, TLR-4 (to 0.52-fold), TNF receptor-associated factor 6, TRAF-6 (to 0.64-fold), nuclear factor kappa-B, NF-κB (to 0.76-fold), vascular cell adhesion molecule 1, VCAM-1 (to 0.71-fold) and intercellular adhesion molecule 1, ICAM-1 (to 0.68-fold). The protein levels of COX-2, TLR-4, p-NF-κB and ICAM-1 were induced by LPS and the açai extract partially reversed this effect in a dose-dependent manner. These results suggest the anti-inflammatory effect of açai polyphenolic extract in intestinal cells are at least in part mediated through the inhibition of ROS and the expression of TLR-4 and NF-κB. Results indicate the potential for açai polyphenolics in the prevention of intestinal inflammation.

  1. Antitumor Activity of Cytotoxic Cyclooxygenase-2 Inhibitors

    PubMed Central

    Uddin, Md. Jashim; Crews, Brenda C.; Xu, Shu; Ghebreselasie, Kebreab; Daniel, Cristina K.; Kingsley, Philip J.; Banerjee, Surajit; Marnett, Lawrence J.

    2017-01-01

    Targeted delivery of chemotherapeutic agents to tumors has been explored as a means to increase the selectivity and potency of cytotoxicity. Most efforts in this area have exploited the molecular recognition of proteins highly expressed on the surface of cancer cells followed by internalization. A related approach that has received less attention is the targeting of intracellular proteins by ligands conjugated to anti-cancer drugs. An attractive target for this approach is the enzyme cyclooxygenase-2 (COX-2), which is highly expressed in a range of malignant tumors. Herein, we describe the synthesis and evaluation of a series of chemotherapeutic agents targeted to COX-2 by conjugation to indomethacin. Detailed characterization of compound 12, a conjugate of indomethacin with podophyllotoxin, revealed highly potent and selective COX-2 inhibition in vitro and in intact cells. Kinetics and X-ray crystallographic studies demonstrated that compound 12 is a slow, tight-binding inhibitor that likely binds to COX-2’s allosteric site with its indomethacin moiety in a conformation similar to that of indomethacin. Compound 12 exhibited cytotoxicity in cell culture similar to that of podophyllotoxin with no evidence of COX-2-dependent selectivity. However, in vivo, compound 12 accumulated selectively in and more effectively inhibited the growth of a COX-2-expressing xenograft compared to a xenograft that did not express COX-2. Compound 12, which we have named chemocoxib A, provides proof-of-concept for the in vivo targeting of chemotherapeutic agents to COX-2, but suggests that COX-2-dependent selectivity may not be evident in cell culture-based assays. PMID:27588346

  2. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  3. Anti-inflammatory flavonoids from Cryptocarya chingii.

    PubMed

    Feng, Rui; Guo, Zhi Kai; Yan, Chun Min; Li, Er Guang; Tan, Ren Xiang; Ge, Hui Ming

    2012-04-01

    Six flavonoids named cryptogiones A-F, and nine known compounds were isolated from an ethanol extract of stems of Cryptocaryachingii. The structures of the compounds were elucidated by interpretation of comprehensive spectroscopic data and X-ray analysis. A majority of these flavonoids contained an acetic acid/lactone moiety, a possible taxonomic marker. Anti-inflammatory effects of the compounds were evaluated using in vitro assays. At 20 μM concentration, three compounds significantly inhibited TNFα-induced NF-кB activation and LPS-induced IL-1β expression.

  4. Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin.

    PubMed

    Lee, Jin-Ah; Ha, Sang Keun; Cho, EunJung; Choi, Inwook

    2015-11-19

    The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

  5. Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study

    PubMed Central

    2011-01-01

    Background The roots of Sophora flavescens (Leguminosae) have been used in East Asian countries as an herbal medicine and a food ingredient for thousands of years. The aim of the present study was to investigate the effects of S. flavescens fermentation on endotoxin-induced uveitis (EIU) in rats. Methods EIU was induced in rats via a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, fermented and non-fermented extracts of S. flavescens (FSE and NFSE, respectively) were administered orally, and the aqueous humor was collected from both eyes 24 hours later. The anti-inflammatory effects of FSE and NFSE were examined in terms of regulation of nuclear factor kappa B (NF-κB) activation and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular cell adhesion molecule (ICAM)-1, and cyclooxygenase-2 (COX-2). The regulation of maleic dialdehyde (MDA) levels and polymorphonuclear cell (PMN) infiltration by FSE and NFSE were also examined. Results Treatment with FSE significantly inhibited LPS-induced increases in IL-1β and TNF-α production and the expression of iNOS, ICAM-1 and COX-2. Moreover, FSE suppressed LPS-induced NF-κB activation, and reduced both MDA levels and infiltration by PMN. Conclusion These results indicate that solid state fermentation may enhance the anti-inflammatory effects of S. flavescens. PMID:22026927

  6. Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin.

    PubMed

    Jung, Hyun-Joo; Song, Yun Seon; Kim, Kyunghoon; Lim, Chang-Jin; Park, Eun-Hee

    2010-02-01

    The present work aimed to assess novel pharmacological properties of ethyl vanillin (EVA) which is used as a flavoring agent for cakes, dessert, confectionary, etc. EVA exhibited an inhibitory activity in the chorioallantoic membrane angiogenesis. Anti-inflammatory activity of EVA was convinced using the two in vivo models, such as vascular permeability and air pouch models in mice. Antinociceptive activity of EVA was assessed using acetic acid-induced writhing model in mice. EVA suppressed production of nitric oxide and induction of inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells. However, EVA could not suppress induction of cyclooxygenase-2 in the LPS-activated macrophages. EVA diminished reactive oxygen species level in the LPS-activated macrophages. EVA also suppressed enhanced matrix metalloproteinase-9 gelatinolytic activity in the LPSactivated RAW264.7 macrophage cells. EVA at the used concentrations couldn't diminish viability of the macrophage cells. Taken together, the anti-angiogenic, anti-inflammatory and anti-nociceptive properties of EVA are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level.

  7. Triterpenoid saponins with anti-inflammatory activities from Ilex pubescens roots.

    PubMed

    Wu, Peng; Gao, Hui; Liu, Jian-Xin; Liu, Liang; Zhou, Hua; Liu, Zhong-Qiu

    2017-02-01

    Seven triterpenoid saponins, named ilexsaponin I-O, along with twelve known ones, were isolated from the roots of Ilex pubescens. The structures of all compounds were elucidated by use of extensive spectroscopic methods (IR, HR-ESI-MS, and 1D and 2D NMR). Sugar residues obtained after acid hydrolysis were identified by TLC and HPLC. The in vitro anti-inflammatory effects of the triterpenoid saponins were also evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among the isolated saponins, seven compounds were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated RAW 264.7 cells. Ilexsaponin I and β-d-glucopyranosyl 3-β-[β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranosyloxy]-olea-12-en-28-oate exerted more potent anti-inflammatory effects than the other compounds tested.

  8. Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells

    PubMed Central

    Li, Xueqin; Shen, Jun; Jiang, Yunyao; Shen, Ting; You, Long; Sun, Xiaobo; Xu, Xudong; Hu, Weicheng; Wu, Haifeng; Wang, Gongcheng

    2016-01-01

    Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent. PMID:27879664

  9. Anti-inflammatory effects of luteolin on experimental autoimmune thyroiditis in mice

    PubMed Central

    Xia, Nan; Chen, Gang; Liu, Min; Ye, Xiaozhen; Pan, Yahui; Ge, Jiuyu; Mao, Yanting; Wang, Hongwei; Wang, Jian; Xie, Sijing

    2016-01-01

    Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis. In the present study, the effect of luteolin on experimental autoimmune thyroiditis (EAT) was analyzed in C57BL/6 mice. Hematoxylin and eosin examination showed that luteolin attenuated lymphocytic infiltration and follicle destruction in thyroid glands. Immunohistochemistry results demonstrated that luteolin significantly reduced the phosphorylation of STAT3 within the thyroid. An in vitro study was carried out in a RAW264.7 macrophage cell line. Western blot findings demonstrated that luteolin significantly inhibited interferon-γ-induced increases in cyclooxygenase 2, phosphorylated STAT1 and phosphorylated STAT3 expression levels and the secretion of the proinflammatory cytokine tumor necrosis factor-α in supernatants. The present findings indicated that luteolin may exert potent anti-inflammatory effects on murine EAT, which may provide a novel therapeutic medication strategy for the early intervention of HT. PMID:28101184

  10. Anti-inflammatory Activity of Grains of Paradise (Aframomum melegueta Schum) Extract

    PubMed Central

    2015-01-01

    The ethanolic extract of grains of paradise (Aframomum melegueta Schum, Zingiberaceae) has been evaluated for inhibitory activity on cyclooxygenase-2 (COX-2) enzyme, in vivo for the anti-inflammatory activity and expression of several pro-inflammatory genes. Bioactivity-guided fractionation showed that the most active COX-2 inhibitory compound in the extract was [6]-paradol. [6]-Shogaol, another compound from the extract, was the most active inhibitory compound in pro-inflammatory gene expression assays. In a rat paw edema model, the whole extract reduced inflammation by 49% at 1000 mg/kg. Major gingerols from the extract [6]-paradol, [6]-gingerol, and [6]-shogaol reduced inflammation by 20, 25 and 38%. respectively when administered individually at a dose of 150 mg/kg. [6]-Shogaol efficacy was at the level of aspirin, used as a positive control. Grains of paradise extract has demonstrated an anti-inflammatory activity, which is in part due to the inhibition of COX-2 enzyme activity and expression of pro-inflammatory genes. PMID:25293633

  11. Two rare antioxidant and anti-inflammatory oleanenes from loop root Asiatic mangrove Rhizophora mucronata.

    PubMed

    Chakraborty, Kajal; Raola, Vamshi Krishna

    2017-03-01

    Two oleanenes, olean-18(19)-en-3β-yl-(3,6-dimethyl-3E,6Z-dienoate) and (13α)-27-frido-olean-14(15)-en-(17α)-furanyl-3β-ol representing a class of rare natural pentacyclic triterpenoids were isolated from the chloroform extract of Asiatic mangrove, Rhizophora mucronata Lam. (Family: Rhizophoraceae). The furanyl oleanene exhibited significantly greater antioxidative activities (IC50 0.73-0.76 mg/mL), than prenylated oleanene (IC50 0.84-0.96 mg/mL) (P < 0.05). No significant differences in anti-5-lipoxygenase activities of these compounds with the synthetic drug ibuprofen was discernable (IC50 0.8-0.9 mg/mL), whilst furanyl oleanene demonstrated significantly greater anti-cyclooxygenase-2 (IC50 0.84 mg/mL) and anti-5-lipoxygenase activities (IC50 0.78 mg/mL) over prenylated oleanene (IC50 > 0.90 mg/mL). These compounds exhibited lesser activity against cyclooxygenase-1 than cyclooxygenase-2 isoform, and therefore, their selectivity indices remained significantly greater (anti-cyclooxygenase-1IC50/anti-cyclooxygenase-2IC50 > 1) than the aspirin (0.02) and ibuprofen (0.44). The lipophilic and steric molecular descriptors were found to occupy a prominent role in determining the bioactivities of the compounds. These previously undescribed oleanenes might serve as potential antioxidative and anti-inflammatory lead molecules in medicinal formulations and food industries.

  12. Antinociceptive and anti-inflammatory effects of essential oil extracted from Chamaecyparis obtusa in mice.

    PubMed

    Park, Yujin; Jung, Seung Min; Yoo, Seung-Ah; Kim, Wan-Uk; Cho, Chul-Soo; Park, Bum-Jin; Woo, Jong-Min; Yoon, Chong-Hyeon

    2015-12-01

    Essential oil extracted from Chamaecyparis obtusa (EOCO) consists of several monoterpenes with anti-inflammatory effects. Monoterpenes are expected to have an analgesic effect through inhibition of pro-inflammatory mediators. The present study investigated the anti-nociceptive and anti-inflammatory effects of EOCO in animal models of pain. Intraperitoneal injection with EOCO (5 or 10mg/kg), aspirin (positive control, 300mg/kg), or DMSO (negative control) was performed 1h before the nociception tests: acetic acid-induced writhing response, formalin test, and hot plate test in mice, and acidic saline-induced allodynia in rats. The expression of pro-inflammatory cytokines and pro-inflammatory enzymes in formalin-injected paws was determined by ELISA and western blotting, respectively. Treatment with EOCO significantly reduced acetic acid-induced writhing and paw-licking time in late response of the formalin tests. The anti-nociceptive effect was comparable with aspirin. However, EOCO did not affect the reaction time of licking of the hind paws or jumping in hot plate test and the mechanical withdrawal thresholds in acidic saline-induced allodynia model. Formalin-injected paws of mice treated with EOCO revealed the down-regulated expression of tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and cyclooxygenase-2, as compared with those of control mice. These data showed the anti-nociceptive and anti-inflammatory effects of EOCO. The pain-relieving effect might be attributed to inhibition of peripheral pain in association with inflammatory response. EOCO could be a useful therapeutic strategy to manage pain and inflammatory diseases.

  13. Anti-inflammatory potential of silk sericin.

    PubMed

    Aramwit, Pornanong; Towiwat, Pasarapa; Srichana, Teerapol

    2013-04-01

    Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats' paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats' tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

  14. Anti-Inflammatory and Pro-Resolving Lipid Mediators

    PubMed Central

    Serhan, Charles N.; Yacoubian, Stephanie; Yang, Rong

    2009-01-01

    The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that non-steroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held to be a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution possessing potent anti-inflammatory and pro-resolving actions. A lipid mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3-polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates in addition to the lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. These new chemical mediator families were coined resolvins and protectins, given their potent bioactions. In this annual review, we present recent advances on the biosynthesis and stereospecific actions of these new pro-resolving mediators, which have also proven to be organ protective and anti-fibrotic. PMID:18233953

  15. Neuroprotective and anti-inflammatory effects of flavonoids isolated from Rhus verniciflua in neuronal HT22 and microglial BV2 cell lines.

    PubMed

    Cho, Namki; Choi, Ji Hoon; Yang, Heejung; Jeong, Eun Ju; Lee, Ki Yong; Kim, Young Choong; Sung, Sang Hyun

    2012-06-01

    The neuroprotective and anti-inflammatory activities of the methanolic extract of Rhus verniciflua Stokes (Anacardiaceae) were investigated with mouse hippocampal and microglial cells. Bioactivity-guided isolation yielded 10 flavonoids including fustin (1), fisetin (2), sulfuretin (3), butein (4), butin (5), eriodictyol (6), morin hydrate (7), quercetin (8), kaempferol (9) and isoliquiritigenin (10). Among the isolated flavonoids, compounds 2-5 significantly protected the murine hippocampal HT22 cells against glutamate-induced neurotoxicity and attenuated reactive oxygen species (ROS) generations. In addition, these flavonoids significantly maintained antioxidative defense systems preserving the activities of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px) and the content of glutathione (GSH) decreased by glutamate insult. These compounds also showed significant inhibitory effects on LPS-induced nitric oxide (NO) production in BV2 cells. Especially, compound 4 dose-dependently suppressed the expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results suggest that these flavonoids possess therapeutic potentials as a multipotent agent against neurodegenerative diseases related to oxidative stress and pathological inflammatory responses.

  16. Use of Selective Cyclooxygenase-2 Inhibitors, Other Analgesics, and Risk of Glioma

    PubMed Central

    Seliger, Corinna; Meier, Christoph R.; Becker, Claudia; Jick, Susan S.; Bogdahn, Ulrich; Hau, Peter; Leitzmann, Michael F.

    2016-01-01

    Background Selective cyclooxygenase-2 (COX-2) inhibitors are analgesic, antipyretic, and anti-inflammatory drugs. They have been found to inhibit the development of glioma in laboratory investigations. Whether these drugs reduce the risk of glioma incidence in humans is unknown. Methods We conducted a matched case-control analysis using the U.K.-based Clinical Practice Research Datalink (CPRD). We identified 2,469 cases matched to 24,690 controls on age, sex, calendar time, general practice, and number of years of active history in the CPRD prior to the index date. We conducted conditional logistic regression analyses to determine relative risks, estimated as odds ratios (ORs) with 95% confidence intervals (CIs) of glioma in relation to use of selective COX-2 inhibitors, adjusted for several confounding variables. Results Use of selective COX-2 inhibitors was unrelated to risk of glioma (adjusted OR for 1–9 versus 0 prescriptions = 1.02; 95% CI = 0.92–1.13, 10–29 versus 0 prescriptions = 1.01; 95% CI = 0.80–1.28, ≥30 versus 0 prescriptions = 1.16; 95% CI = 0.86–1.55). Trends for increasing numbers of prescriptions for other non-steroidal anti-inflammatory drugs (NSAIDs), and non-NSAID analgesics were also not associated with glioma risk. Conclusion Further epidemiologic studies are needed to confirm the null relation of use of selective COX-2 inhibitors to glioma risk and to explain the discrepancy between laboratory investigations and our observational study. Impact: Use of selective COX-2 inhibitors is unrelated to glioma risk. PMID:26871579

  17. Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition?

    PubMed

    Davies, N M

    1997-12-01

    Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the 2,6-disubstituted naphthyl-alkanone class. Nabumetone is metabolised to an active metabolite 6-methoxy-2-napthylacetic acid (6-MNA) which is a relatively selective cyclo-oxygenase-2 inhibitor that has anti-inflammatory and analgesic properties. Nabumetone and its metabolites bind extensively to plasma albumin. Nabumetone is eliminated following biotransformation to 6-MNA, which does not undergo enterohepatic circulation and the respective glucoroconjugated metabolites are excreted in urine. Substantial concentrations of 6-MNA are attained in synovial fluid, which is he proposed site of action in chronic inflammatory arthropathies. A smaller area under the plasma concentration-time curve (AUC) is evident at steady state as compared with a single dose; this is possibly due to an increase in the volume of distribution and saturation of protein binding. Relationships between 6-MNA concentrations and the therapeutic and toxicological effects have yet to be elucidated for this NSAID. Renal failure significantly reduces 6-MNA elimination but steady-state concentrations of 6-MNA are not increased, possibly because of nonlinear protein binding. Elderly patients with osteoarthritis demonstrate decreased elimination and increased plasma concentrations of nabumetone as compared with young healthy volunteers. Rheumatic disease activity also influences 6-MNA plasma concentrations, as patients with more active disease and lower serum albumin concentrations demonstrate a lower area under the plasma concentration versus time curve. A reduced bioavailability of 6-MNA in patients with severe hepatic impairment is also evident. Dosage adjustment may be required in the elderly, patients with active rheumatic disease and those with hepatic impairment, but not in patients with mild-to-moderate renal failure.

  18. Anti-inflammatory effects of fibrates: an overview.

    PubMed

    Tziomalos, Konstantinos; Athyros, Vasilios G; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2009-01-01

    Inflammation plays an important role in the pathogenesis of atherosclerosis. Several cardiovascular drugs exert anti-inflammatory effects and accumulating data suggest that fibrates also share this property. This review summarizes the mechanisms implicated in the anti-inflammatory actions of fibrates. We also provide an overview of the existing clinical studies addressing the effects of fibrates on markers of inflammation. Several, but not all, studies reported that fibrates exert anti-inflammatory actions. The small number of patients included in some studies, as well as differences in diagnoses and duration of follow up might partly explain this discrepancy. It is also possible that fibrates differ substantially in terms of anti-inflammatory effects. It is not clear whether an anti-inflammatory action of fibrates is clinically relevant. Future studies should assess whether the anti-inflammatory actions of fibrates (or for that matter, other drugs) will translate into a reduced risk of vascular disease.

  19. Biogenic guaianolide-type sesquiterpene lactones with antioxidative and anti-inflammatory properties from natural mangrove hybrid Rhizophora annamalayana.

    PubMed

    Raola, Vamshi Krishna; Chakraborty, Kajal

    2017-02-24

    Previously undescribed guaianolide-type sesquiterpene lactones were isolated from the chloroform fraction of the natural hybrid mangrove Rhizophora annamalayana, and were characterised as (Z)-3α,4,5,6-tetrahydro-5α-isobutyl-2β-(methoxymethyl)-7-methyl-3H-cyclohepta[b]carbolactone (1) and (7Z)-isopentyl 3α,4,5,6,7,8-hexahydro-2β-((E)-11-methylbut-10-enyl)-1-oxo-2H-cyclohepta[b]furan-6-carboxylate (2). Compound 2 displayed greater antioxidative activities {1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azino-bis-3 ethylbenzothiozoline-6-sulphonic acid diammonium salt (ABTS), IC50 0.65 and 0.62 mg/mL, respectively)} compared to 1 (IC50 0.83 and 1.14 mg/mL, respectively) (p < 0.05). Compound 2 recorded no significant difference in DPPH(.) scavenging activities (IC50 0.65 mg/mL) compared to α-tocopherol (IC50 0.63 mg/mL). Pro-inflammatory 5-lipoxygenase inhibitory activity of 2 was found to be comparable (IC50 0.98 mg/mL) to that displayed by synthetic anti-inflammatory drug ibuprofen (IC50 0.93 mg/mL). Compound 2 showed significantly greater selectivity index (anti-cyclooxygenase-1/anti-cyclooxygenase-2 = 2.15) than non-steroidal anti-inflammatory ibuprofen (<0.5) (p < 0.05), and therefore, might be used as selective cyclooxygenase-2 inhibitor. The hitherto undescribed guaianolide lactones might be used as potential anti-inflammatory and antioxidative pharmacophore leads.

  20. Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti-inflammatory potential of apigenin.

    PubMed

    Choi, Jae Sue; Islam, Md Nurul; Ali, Md Yousof; Kim, Eon Ji; Kim, Young Myeong; Jung, Hyun Ah

    2014-02-01

    Apigenin has gained particular interests in recent years as a beneficial and health promoting agent because of its low intrinsic toxicity. Vitexin and isovitexin, naturally occurring C-glycosylated derivatives of apigenin, have been known to possess potent anti-diabetic, anti-Alzheimer's disease (anti-AD), and anti-inflammatory activities. The present study was designed to investigate the anti-diabetic, anti-AD, and anti-inflammatory potential of apigenin and its two C-glycosylated derivatives, vitexin and isovitexin by in vitro assays including rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation endproducts (AGEs), protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor (APP) cleaving enzyme 1 (BACE1), and nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, isovitexin was found as the most potent inhibitor against RLAR, HRAR, AGE, AChE, and BChE while vitexin showed the most potent PTP1B inhibitory activity. Despite the relatively weak anti-diabetic and anti-AD potentials, apigenin showed powerful antiinflammatory activity by inhibiting NO production and iNOS and COX-2 expression while vitexin and isovitexin were inactive. Therefore, it could be speculated that C-glycosylation of apigenin at different positions might be closely linked to relative intensity of anti-diabetic, anti-AD, and anti-inflammatory potentials.

  1. Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action.

    PubMed

    Preethi, Korengath Chandran; Kuttan, Girija; Kuttan, Ramadasan

    2009-02-01

    Calendula officinalis flower extract possessed significant anti-inflammatory activity against carrageenan and dextran-induced acute paw edema. Oral administration of 250 and 500 mg/kg body weight Calendula extract produced significant inhibition (50.6 and 65.9% respectively) in paw edema of animals induced by carrageenan and 41.9 and 42.4% respectively with inflammation produced by dextran. In chronic anti-inflammatory model using formalin, administration of 250 and 500 mg/kg body weight Calendula extract produced an inhibition of 32.9 and 62.3% respectively compared to controls. TNF-alpha production by macrophage culture treated with lipopolysaccharide (LPS) was found to be significantly inhibited by Calendula extract. Moreover, increased levels of proinflammatory cytokines IL- 1beta, IL-6, TNF-alpha and IFN-gamma and acute phase protein, C- reactive protein (CRP) in mice produced by LPS injection were inhibited significantly by the extract. LPS induced cyclooxygenase-2 (Cox-2) levels in mice spleen were also found to be inhibited by extract treatment. The results showed that potent anti-inflammatory response of C. officinalis extract may be mediated by the inhibition of proinflammatory cytokines and Cox-2 and subsequent prostaglandin synthesis.

  2. Antioxidant, Antinociceptive, and Anti-Inflammatory Activities from Actinidia callosa var. callosa In Vitro and In Vivo

    PubMed Central

    Liao, Jung-Chun; Deng, Jeng-Shyan; Lin, Ying-Chih; Lee, Chao-Ying; Lee, Min-Min; Hou, Wen-Chi; Huang, Shyh-Shyun; Huang, Guan-Jhong

    2012-01-01

    Actinidia callosa var. callosa has been widely used to treat antipyretic, analgesic, anti-inflammation, abdominal pain, and fever in Taiwan. The aim of this study was to evaluate the antioxidant, antinociceptive, and anti-inflammatory lipopolysaccharide-(LPS-)induced nitric oxide (NO) production in RAW264.7 macrophages and pawedema induced by λ-carrageenan activities of the methanol extract from A. callosa. In HPLC analysis, the fingerprint chromatogram of ethyl-acetate fraction of A. callosa (EAAC) was established. EAAC showed the highest TEAC and DPPH radical scavenging activities, respectively. We evaluated that EAAC and the reference compound of catechin and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Treatment of male ICR mice with EAAC significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of EAAC showed a concentration-dependent inhibition on paw edema development after Carr treatment in mice. Anti-inflammatory mechanisms of EAAC might be correlated to the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) in vitro and in vivo. Overall, the results showed that EAAC demonstrated antioxidant, antinociceptive, and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain. PMID:23227095

  3. Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages.

    PubMed

    Park, Mi-Young; Kwon, Hoon-Jeong; Sung, Mi-Kyung

    2009-04-23

    The aloe ingredients responsible for physiological effects and the concentrations required to exert their biological activities are not fully understood. This study compares the anti-inflammatory effects of aloin and aloe-emodin with other polyphenols. Our results demonstrated that aloe-emodin dose-dependently inhibited inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production at 5-40 microM. In addition, the levels of cyclooxygenase-2 (COX-2) mRNA and prostaglandin E2 (PGE2) production were suppressed by 40 microM aloe-emodin. Aloin also suppressed the production of NO at 5-40 microM, although it did not suppress PGE2 production. The present results indicate that aloin and aloe-emodin possibly suppress the inflammatory responses by blocking iNOS and COX-2 mRNA expression. The anti-inflammatory effect of aloe-emodin was comparable to that of kaempferol and quercetin, indicating aloe-emodin as a possible key constituent responsible for the anti-inflammatory activity of aloe.

  4. 17-oxo-DHA displays additive anti-inflammatory effects with fluticasone propionate and inhibits the NLRP3 inflammasome

    PubMed Central

    Cipollina, Chiara; Di Vincenzo, Serena; Siena, Liboria; Di Sano, Caterina; Gjomarkaj, Mark; Pace, Elisabetta

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function associated with increased local and systemic inflammatory markers, such as TNFα and IL-1β. Glucocorticoids are used to treat this chronic disease, however their efficacy is low and new drugs are very much required. 17-oxo-DHA is a cyclooxygenase-2-dependent, electrophilic, α,β-unsaturated keto-derivative of docosahexaenoic acid with anti-inflammatory properties. We evaluated the action of 17-oxo-DHA alone or in combination with the steroid fluticasone propionate (FP) in peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy individuals exposed to lipopolysaccharide. We show that PBMCs from COPD patients released higher levels of TNFα and IL-1β compared to controls. 17-oxo-DHA displayed strong anti-inflammatory effects. The addition of 17-oxo-DHA in combination with FP showed enhanced anti-inflammatory effects through the modulation of transcriptional and post-transcriptional mechanisms. 17-oxo-DHA, but not FP, was able to suppress the release of mature IL-1β through inhibition of the NLRP3 inflammasome. Furthermore, 17-oxo-DHA inhibited inflammasome-dependent degradation of the glucocorticoid receptor (GR). Our findings suggest that 17-oxo-DHA in combination with FP or other steroids might achieve higher therapeutic efficacy than steroids alone. Combined treatment might be particularly relevant in those conditions where increased inflammasome activation may lead to GR degradation and steroid-unresponsive inflammation. PMID:27883019

  5. Chemical characterization and in vivo anti-inflammatory activities of Actinidia callosa var. ephippioides via suppression of proinflammatory cytokines.

    PubMed

    Liao, Jung-Chun; Huang, Shyh-Shyun; Deng, Jeng-Shyan; Lee, Chao-Ying; Lin, Ying-Chih; Huang, Guan-Jhong

    2013-01-01

    Actinidia callosa var. ephippioides (ACE) has been widely used to treat anti-pyretic, antinociceptive, anti-inflammation, abdominal pain and fever in Taiwan. This study aims to determine the mechanism of anti-inflammatory activities of ethyl acetate fraction of ACE (EA-ACE) using a model of λ-carrageenan (Carr)-induced paw edema in mouse model. In HPLC analysis, chemical characterization of EA-ACE was established. In order to investigate the anti-inflammatory mechanism of EA-ACE, we have detected the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the paw edema. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were evaluated. Chemical characterization from HPLC indicated that EA-ACE contains betulinic acid, ursolic acid and oleanolic acid. In the anti-inflammatory test, EA-ACE decreased the paw edema after Carr administration, increased the activities of CAT, SOD, and GPx and decreased the MDA level in the edema paw at the 5th hr after Carr injection. EA-ACE affects the serum NO, TNF-α, and IL-1β levels at the 5th hr after Carr injection. EA-ACE decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions by Western blotting. Actinidia callosa var. ephippioides have the potential to provide a therapeutic approach to inflammation-associated disorders.

  6. Intravital Microscopic Methods to Evaluate Anti-inflammatory Effects and Signaling Mechanisms Evoked by Hydrogen Sulfide

    PubMed Central

    Zuidema, Mozow Y.; Korthuis, Ronald J.

    2016-01-01

    Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule with potent anti-inflammatory properties. Exogenous application of H2S donors, administered either acutely during an inflammatory response or as an antecedent preconditioning intervention that invokes the activation of anti-inflammatory cell survival programs, effectively limits leukocyte rolling, adhesion and emigration, generation of reactive oxygen species, chemokine and cell adhesion molecule expression, endothelial barrier disruption,capillary perfusion deficits, and parenchymal cell dysfunction and injury. This chapter focuses on intravital microscopic methods that can be used to assess the anti-inflammatory effects exerted by H2S, as well as to explore the cellular signaling mechanisms by which this gaseous molecule limits the aforementioned inflammatory responses. Recent advances include use of intravital multiphoton microscopy and optical biosensor technology to explore signaling mechanisms in vivo. PMID:25747477

  7. Comparison of beneficial actions of non-steroidal anti-inflammatory drugs to flavonoids.

    PubMed

    Conti, P; Varvara, G; Murmura, G; Tete, S; Sabatino, G; Saggini, A; Rosati, M; Toniato, E; Caraffa, A; Antinolfi, P; Pandolfi, F; Potalivo, G; Galzio, R; Theoharides, T C

    2013-01-01

    Inflammation is involved in increasing number of diseases necessitating the development of new, effective and safe treatments. Non steroidal anti-inflammatory drugs (NSAIDs) have been helpful in many instances, but they only inhibit cyclooxygenase (COX), but not the generation or actions of cytokines. Instead, some natural flavonoids have multiple anti-inflammatory effects, including COX inhibition, and a much safer profile. Increasing evidence indicates that inflammation plays a critical role in the pathogenesis of many diseases that also involve mast cells. Consequently, the need for new, effective and safe anti-inflammatory drugs is all the more urgent. Corticosteroids are quite potent, but have many adverse effects such as increased risk of infections, osteoporosis, glaucoma and depression. Biological agents such anti-TNF are useful in certain conditions, such as rheumatoid arthritis and psoriasis, but has been associated with increased risk of infection and leukemia.

  8. Adiponectin as an anti-inflammatory factor

    PubMed Central

    Ouchi, Noriyuki; Walsh, Kenneth

    2009-01-01

    Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this reviews, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an antiinflammatory marker. PMID:17343838

  9. Review of Anti-Inflammatory Herbal Medicines

    PubMed Central

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. PMID:27247570

  10. Corneal reepithelialization and anti-inflammatory agents.

    PubMed Central

    Srinivasan, B D

    1982-01-01

    These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects. Images FIGURE 3 a FIGURE 3 b PMID:6763806

  11. Flavonoids as anti-inflammatory agents.

    PubMed

    Serafini, Mauro; Peluso, Ilaria; Raguzzini, Anna

    2010-08-01

    Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases. However, the mechanism of action and the components involved in this effect have not been identified clearly. In recent years, the scientific community has agreed to focus its attention on a class of secondary metabolites extensively present in a wide range of plant foods: the flavonoids, suggested as having different biological roles. The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein. Molecular activities of flavonoids include inhibition of transcription factors such as NF-kappaB and activating protein-1 (AP-1), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the in vitro evidence might be somehow of limited impact due to the non-physiological concentrations utilized and to the fact that in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food. Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids. Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.

  12. Development of anti-inflammatory drugs - the research and development process.

    PubMed

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines.

  13. Effect of phosphodiesterase 4 inhibitors on NFAT-dependent cyclooxygenase-2 expression in human T lymphocytes.

    PubMed

    Jimenez, José L; Iñiguez, Miguel A; Muñoz-Fernández, M Angeles; Fresno, Manuel

    2004-12-01

    Transcriptional induction of cyclooxygenase-2 (COX-2) occurs early after T cell receptor triggering and has functional implications in inflammation. Here, we show that phosphodiesterase (PDE)-4 inhibitors block COX-2 induction and prostaglandin synthesis in activated T cells. COX-2 inhibition by PDE4 inhibitors occurs mainly at the transcriptional level. Two response elements for the nuclear factor of activated T cells (NFAT) in the COX-2 promoter were required for inhibition by these drugs. PDE4 inhibitors did not affect NFAT nuclear translocation upon T cell activation; rather they prevented NFAT binding to DNA and induction of the transactivation function of GAL4-NFAT. These effects seem to be cAMP/PKA independent as they were not mimicked by the permeable analog dBcAMP or by forskolin, neither can be reverted by the PKA inhibitors H89 or KT-5720. These results may explain some of the anti-inflammatory properties of PDE4 inhibitors through the blockade of NFAT-mediated transactivation of pro-inflammatory genes such as COX-2.

  14. Sinomenine inhibits proliferation of SGC-7901 gastric adenocarcinoma cells via suppression of cyclooxygenase-2 expression

    PubMed Central

    LV, YIFEI; LI, CHANGSHUN; LI, SHUANG; HAO, ZHIMING

    2011-01-01

    Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum. Results of studies have shown that the anti-inflammatory, immunosuppressive and anti-arthritic effects of SIN are partially attributed to the inhibition of cyclooxygenase-2 (COX-2) expression. COX-2 overexpression is associated with enhanced proliferation and angiogenesis of gastric cancer (GC). SGC-7901 cells were treated with different concentrations of SIN in order to observe its effect on the proliferation of human gastric adenocarcinoma cells and to explore the potential underlying molecular mechanism via the detection of COX-2 expression. Celecoxib was used as the positive control. Morphological alterations of the cells were observed microscopically. Cell proliferation was evaluated using MTT assay. COX-2 expression was detected using semi-quantitative RT-PCR and Western blotting. The results showed that SIN inhibited the proliferation of SGC-7901 cells in a time- and dose-dependent manner. In the presence of SIN or celecoxib, SGC-7901 cells became round and detached morphologically, indicating cell apoptosis. The expression of COX-2 was inhibited by SIN in a dose-dependent manner at both the mRNA and protein levels. Our findings indicate that the protective effects of SIN are mediated through the inhibition of COX-2 expression. These findings suggest a novel therapy to treat inflammation-mediated gastric adenocarcinomata. PMID:22848259

  15. Potential anti-inflammatory natural products from marine algae.

    PubMed

    Fernando, I P Shanura; Nah, Jae-Woon; Jeon, You-Jin

    2016-12-01

    Inflammatory diseases have become one of the leading causes of health issue throughout the world, having a considerable influence on healthcare costs. With the emerging developments in natural product, synthetic and combinatorial chemistry, a notable success has been achieved in discovering natural products and their synthetic structural analogs with anti-inflammatory activity. However, many of these therapeutics have indicated detrimental side effects upon prolonged usage. Marine algae have been identified as an underexplored reservoir of unique anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides, terpenes, fatty acids, proteins and several other bioactives. Consumption of these marine algae could provide defense against the pathophysiology of many chronic inflammatory diseases. With further investigation, algal anti-inflammatory phytochemicals have the potential to be used as therapeutics or in the synthesis of structural analogs with profound anti-inflammatory activity with reduced side effects. The current review summarizes the latest knowledge about the potential anti-inflammatory compounds discovered from marine algae.

  16. A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects

    PubMed Central

    Chen, Chun-Hong; Chen, Nan-Fu; Feng, Chien-Wei; Cheng, Shu-Yu; Hung, Han-Chun; Tsui, Kuan-Hao; Hsu, Chi-Hsin; Sung, Ping-Jyun; Chen, Wu-Fu; Wen, Zhi-Hong

    2016-01-01

    Background: Our previous in vitro results demonstrated that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine-induced cytotoxicity and apoptosis in a human neuroblastoma cell line, SH-SY5Y, and suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 in lipopolysaccharide-stimulated macrophage cells. The neuroprotective and anti-inflammatory effects of 11-dehydrosinulariolide may be suitable for treating spinal cord injury (SCI). Methods: In the present study, Wistar rats were pretreated with 11-dehydrosinulariolide or saline through intrathecal injection after a thoracic spinal cord contusion injury induced using a New York University (NYU) impactor. The apoptotic cells were assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression and localization of proinflammatory, apoptosis-associated and cell survival-related pathway proteins were examined through immunoblotting and immunohistochemistry. Results: 11-Dehydrosinulariolide attenuated SCI-induced cell apoptosis by upregulating the antiapoptotic protein Bcl-2 and cell survival-related pathway proteins p-Akt and p-ERK, 8 h after SCI. Furthermore, the transcription factor p-CREB, which regulates Bcl-2 expression, was upregulated after 11-dehydrosinulariolide treatment. On day 7 after SCI, 11-dehydrosinulariolide exhibited an anti-inflammatory effect, attenuating SCI-induced upregulation of the inflammatory proteins iNOS and tumor necrosis factor-α. 11-Dehydrosinulariolide also induced an increase in the expression of arginase-1 and CD206, markers of M2 microglia, in the injured spinal cord on day 7 after SCI. Thus, the anti-inflammatory effect of 11-dehydrosinulariolide may be related to the promotion of an alternative pathway of microglia activation. Conclusion: The results show that 11-dehydrosinulariolide exerts antiapoptotic effects at 8 h after SCI and anti-inflammatory effects at 7 days after SCI. We consider that this

  17. Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-κB activation.

    PubMed

    Luo, Pei; Wong, Yuen Fan; Ge, Lin; Zhang, Zhi Feng; Liu, Yuan; Liu, Liang; Zhou, Hua

    2010-12-01

    Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anticarcinogenic, anti-inflammatory, and analgesic activities. However, the mechanism underlying its anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg. We also examined the role of nuclear factor κB (NF-κB) and proinflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various proinflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2). PL reduced the number of writhing episodes of mice induced by the intraperitoneal injection of acetic acid, but it did not reduce the writhing episode numbers induced by MgSO(4) in mice or prolong the tail-flick reaction time of rats to noxious thermal pain. Mechanistic studies showed that PL effectively decreased the production of the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α. It also inhibited the expression of the proinflammatory mediators inducible nitric-oxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of κBα phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-κB. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.

  18. Synthesis of new 2,3-dihydroquinazolin-4(1H)-one derivatives for analgesic and anti-inflammatory evaluation.

    PubMed

    El-Sabbagh, Osama I; Ibrahim, Samy M; Baraka, Mohamed M; Kothayer, Hend

    2010-05-01

    Starting from isatoic anhydrides, several new 2,3-dihydroquinazolin-4(1H)-one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti-inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic-acid-induced writhing-response method and carrageenan-induced edema method, respectively. The study showed that the chalcones bearing a 4-chlorophenyl group 4c or 4-nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N-phenyl pyrazole bearing 4-methoxy phenyl group 5b showed a higher anti-inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygenase-2 inhibitor celecoxib.

  19. Anti-inflammatory activity of the oriental herb medicine, Arisaema cum Bile, in LPS-induced PMA-differentiated THP-1 cells.

    PubMed

    Ahn, Chang-Bum; Je, Jae-Young

    2012-06-01

    Arisaema cum Bile is widely used as a folk medicine in Korea. However, the systematic biological properties of Arisaema cum Bile have seldom been addressed. In this study, we evaluated the anti-inflammatory activity of Arisaema cum Bile extract on lipopolysaccharide (LPS)-induced inflammation in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages. The Arisaema cum Bile extract markedly inhibited the production of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and also suppressed the mRNA and protein expressions of these cytokines. Furthermore, the Arisaema cum Bile extract also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and gene expressions in PMA-differentiaed THP-1 macrophages. These results suggest that Arisaema cum Bile extract may have potential for development into an effective anti-inflammatory agent, and/or as an ingredient of functional foods.

  20. Antidepressant augmentation with anti-inflammatory agents.

    PubMed

    Andrade, Chittaranjan

    2014-09-01

    Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.

  1. Anti-Inflammatory Constituents from Bidens frondosa.

    PubMed

    Le, Jiamei; Lu, Wenquan; Xiong, Xiaojuan; Wu, Zhijun; Chen, Wansheng

    2015-10-09

    A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-D-glucopyranoside (1), a new phenylpropanoid glucoside 2'-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3',4'-trihydroxyflavone-7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (3), have been isolated from Bidens frondosa together with fifty-three known compounds 4-56. The structures of these compounds were established by spectroscopic methods. mainly ESIMS, 1D- and 2D-NMR spectroscopic data. and comparison with literature data. Compounds 1-34, 36, 39, 43, 47, 51, and 52 were tested for inhibition of nuclear factor kappa B (NF-κB) in 293-NF-κB-luciferase report cell line induced by lipopolysaccharide (LPS), and compounds 1, 2, 3, 9, 15, 21, 24 and 51 were tested for the production of TNF-α, IL-1β, IL-6, IL-10 in RAW 264.7 macrophages induced by LPS. In conclusion, the isolated compounds 1, 2, 3, 9, 15, 21, 24 and 51 exhibited significant activity in anti-inflammatory activity assays.

  2. 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.

  3. Anti-inflammatory activity of edible brown alga Saccharina japonica and its constituents pheophorbide a and pheophytin a in LPS-stimulated RAW 264.7 macrophage cells.

    PubMed

    Islam, Md Nurul; Ishita, Ishrat Jahan; Jin, Seong Eun; Choi, Ran Joo; Lee, Chan Mee; Kim, Yeong Shik; Jung, Hyun Ah; Choi, Jae Sue

    2013-05-01

    Anti-inflammatory activity of Saccharina japonica and its active components was evaluated via in vitro inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression in RAW 264.7 murine macrophage cells. Since the methanolic extract of S. japonica showed strong anti-inflammatory activity, it was fractionated with several solvents. Among the fractions, the ethyl acetate fraction demonstrated the highest inhibition of LPS-induced NO production (IC50=25.32μg/mL), followed by the CH2Cl2 fraction (IC50=75.86μg/mL). Considering the yield and anti-inflammatory potential together, the CH2Cl2 fraction was selected for chromatographic separation to yield two active porphyrin derivatives, pheophorbide a and pheophytin a, together with an inactive fucoxanthin. In contrast to fucoxanthin, pheophorbide a and pheophytin a showed dose-dependent inhibition against LPS-induced NO production at nontoxic concentrations in RAW 264.7 cells. Both compounds also suppressed the expression of iNOS proteins, while they did not inhibit the COX-2 expression in LPS-stimulated macrophages. These results indicate that pheophorbide a and pheophytin a are two important candidates of S. japonica as anti-inflammatory agents which can inhibit the production of NO via inhibition of iNOS protein expression. Thus, these compounds hold great promise for use in the treatment of various inflammatory diseases.

  4. Geranyl flavonoid derivatives from the fresh leaves of Artocarpus communis and their anti-inflammatory activity.

    PubMed

    Hsu, Chin-Lin; Chang, Fang-Rong; Tseng, Pei-Yu; Chen, Yi-Fen; El-Shazly, Mohamed; Du, Ying-Chi; Fang, Song-Chwan

    2012-06-01

    Breadfruit (Artocarpus communis) is a widely distributed crop in tropical and subtropical regions of the world. It is used in Southeast Asia and India to treat several inflammatory disorders. The aim of this study was to investigate the presence of anti-inflammatory flavonoids in A. communis leaves. Three new geranyl flavonoids, arcommunol C (1), arcommunol D (3), and 5'-geranyl-3,4,2',4'-tetrahydroxychalcone (5), together with four known compounds, prostratol (2), arcommunol E (4), 3'-geranyl-3,4,2',4'-tetrahydroxydihydrochalcone (6), and 3'-geranyl-3,4,2',4'-tetrahydroxychalcone (7), were isolated from the leaves of A. communis. Compound 4 was isolated for the first time from natural sources. The anti-inflammatory activity of the isolated compounds (1-7) was evaluated by determining their inhibitory activity on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 2, 3, and 4 suppressed the LPS-induced production of nitric oxide (NO) in RAW 264.7 cells with IC50 values of 8.13 ± 0.17, 18.45 ± 2.15, and 22.74 ± 1.74 µM, respectively. Furthermore, 2 decreased lipopolysaccharide (LPS)-mediated induction of protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. It was also found that 2 suppressed LPS-induced phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) signaling.

  5. Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba in animal models.

    PubMed

    Li, Yu-Cui; Xian, Yan-Fang; Ip, Siu-Po; Su, Zi-Ren; Su, Ji-Yan; He, Jing-Jin; Xie, Qing-Feng; Lai, Xiao-Ping; Lin, Zhi-Xiu

    2011-12-01

    Pogostemonis Herba has long been used in traditional Chinese medicine for the treatment of inflammatory disorders. Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, is known to possess a variety of pharmacological activities. The present study aimed to investigate the in vivo anti-inflammatory effect of PA using two common inflammatory animal models i.e., xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. The degree of edema in both inflammatory animals, as well as the protein and mRNA expression of some inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E₂ (PGE₂) and nitric oxide (NO) in the hind paw of carrageenan-treated rats were measured. Results showed that PA (10-40 mg/kg) significantly inhibited the ear edema induced by xylene in mice and the paw edema induced by carrageenan in rats. In addition, treatment with PA (10-40 mg/kg) also dose-dependently decreased the production of TNF-α, IL-1β, PGE₂ and NO in the hind paw of carrageenan-treated rats. Furthermore, PA treatment also suppressed the mRNA expression of TNF-α, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hind paw of carrageenan-treated rats. These results suggest that PA possesses potent anti-inflammatory activity, which may be mediated, at least in part, by down-regulating the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-1β, iNOS and COX-2.

  6. Anti-Inflammatory Effects of Agrimoniin-Enriched Fractions of Potentilla erecta.

    PubMed

    Hoffmann, Julia; Casetti, Federica; Bullerkotte, Ute; Haarhaus, Birgit; Vagedes, Jan; Schempp, Christoph M; Wölfle, Ute

    2016-06-18

    Potentilla erecta (PE) is a small herbaceous plant with four yellow petals belonging to the Rosaceae family. The rhizome of PE has traditionally been used as an antidiarrheal, hemostatic and antihemorrhoidal remedy. PE contains up to 20% tannins and 5% ellagitannins, mainly agrimoniin. Agrimoniin is a hydrolyzable tannin that is a potent radical scavenger. In this study we tested the anti-inflammatory effect of four PE fractions with increasing amounts of agrimoniin obtained by Sephadex column separation. First, we analyzed in HaCaT keratinocytes the expression of cyclooxygenase-2 (COX-2) induced by ultraviolet-B (UVB) irradiation. As COX-2 catalyzes the metabolism of arachidonic acid to prostanoids such as PGE₂, we also measured the PGE₂ concentration in cell culture supernatants. PE inhibited UVB-induced COX-2 expression in HaCaT cells and dose-dependently reduced PGE₂. The PE fraction with the highest agrimoniin amount (PE4) was the most effective in this experiment, whereas fraction PE1 containing mainly sugars had no effect. PE4 also dose dependently inhibited the phosphorylation of the epidermal growth factor receptor (EGFR) which plays a crucial role in UVB-mediated COX-2 upregulation. A placebo-controlled UV-erythema study with increasing concentrations of PE4 demonstrated a dose dependent inhibition of UVB-induced inflammation in vivo. Similarly, PE4 significantly reduced UVB-induced PGE₂ production in suction blister fluid in vivo. In summary, PE fractions with a high agrimoniin content display anti-inflammatory effects in vitro and in vivo in models of UVB-induced inflammation.

  7. Anti-inflammatory glucocorticoids: changing concepts.

    PubMed

    Newton, Robert

    2014-02-05

    Despite being the most effective anti-inflammatory treatment for chronic inflammatory diseases, the mechanisms by which glucocorticoids (corticosteroids) effect repression of inflammatory gene expression remain incompletely understood. Direct interaction of the glucocorticoid receptor (NR3C1) with inflammatory transcription factors to repress transcriptional activity, i.e. transrepression, represents one mechanism of action. However, transcriptional activation, or transactivation, by NR3C1 also represents an important mechanism of glucocorticoid action. Glucocorticoids rapidly and profoundly increase expression of multiple genes, many with properties consistent with the repression of inflammatory gene expression. For example: the dual specificity phosphatase, DUSP1, reduces activation of mitogen-activated protein kinases; glucocorticoid-induced leucine zipper (TSC22D3) represses nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) transcriptional responses; inhibitor of κBα (NFKBIA) inhibits NF-κB; tristraprolin (ZFP36) destabilises and translationally represses inflammatory mRNAs; CDKN1C, a cell cycle regulator, may attenuate JUN N-terminal kinase signalling; and regulator of G-protein signalling 2 (RGS2), by reducing signalling from Gαq-linked G protein-coupled receptors (GPCRs), is bronchoprotective. While glucocorticoid-dependent transrepression can co-exist with transactivation, transactivation may account for the greatest level and most potent repression of inflammatory genes. Equally, NR3C1 transactivation is enhanced by β2-adrenoceptor agonists and may explain the enhanced clinical efficacy of β2-adrenoceptor/glucocorticoid combination therapies in asthma and chronic obstructive pulmonary disease. Finally, NR3C1 transactivation is reduced by inflammatory stimuli, including respiratory syncytial virus and human rhinovirus. This provides an explanation for glucocorticoid resistance. Continuing efforts to understand roles for glucocorticoid

  8. Cannabinoids as novel anti-inflammatory drugs.

    PubMed

    Nagarkatti, Prakash; Pandey, Rupal; Rieder, Sadiye Amcaoglu; Hegde, Venkatesh L; Nagarkatti, Mitzi

    2009-10-01

    Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.

  9. Structural investigation of chitosan-based microspheres with some anti-inflammatory drugs

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Dragan, Felicia; Bende, A.; Borodi, Gh.; Bratu, I.

    2011-06-01

    The use of chitosan as an excipient in oral formulations, as a drug delivery vehicle for ulcerogenic anti-inflammatory drugs and as base in polyelectrolyte complex systems, to prepare solid release systems as sponges was investigated. The preparation by double emulsification of chitosan hydrogels carrying diclofenac, acetyl-salycilic acid and hydrocortisone acetate as anti-inflammatory drugs is reported. The concentration of anti-inflammatory drug in the chitosan hydrogel generating the sponges was 0.08 mmol. Chitosan-drug loaded sponges with anti-inflammatory drugs were prepared by freeze-drying at -60 °C and 0.009 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared and ultraviolet-visible spectroscopy, spectrofluorimetry, differential scanning calorimetry and X-ray diffractometry. The results indicated that the drug molecules are forming temporary chelates in chitosan hydrogels and sponges. Electron paramagnetic resonance demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan-drug supramolecular cross-linked assemblies.

  10. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease.

    PubMed

    García-Lafuente, Ana; Guillamón, Eva; Villares, Ana; Rostagno, Mauricio A; Martínez, José Alfredo

    2009-09-01

    Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.

  11. Expression of cyclooxygenase-2, alpha 1-acid-glycoprotein and inducible nitric oxide synthase in the developing lesions of murine leprosy.

    PubMed

    Silva Miranda, Mayra; Rodríguez, Kendy Wek; Martínez Cordero, Erasmo; Rojas-Espinosa, Oscar

    2006-12-01

    Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression.

  12. Expression of cyclooxygenase-2, alpha 1-acid-glycoprotein and inducible nitric oxide synthase in the developing lesions of murine leprosy

    PubMed Central

    Silva Miranda, Mayra; Rodríguez, Kendy Wek; Martínez Cordero, Erasmo; Rojas-Espinosa, Oscar

    2006-01-01

    Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression. PMID:17222216

  13. [Non steroidal anti-inflammatory drugs and rheumatic diseases].

    PubMed

    Cossermelli, W; Pastor, E H

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

  14. Anti-inflammatory and analgesic activities of Melanthera scandens

    PubMed Central

    Okokon, Jude E; Udoh, Anwanga E; Frank, Samuel G; Amazu, Louis U

    2012-01-01

    Objective To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens). Methods The crude leaf extract (39–111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property. Results The extract caused a significant (P<0.05 – 0.001) dose-dependent reduction of inflammation and pains induced by different agents used. Conclusions The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant. PMID:23569885

  15. Update on rosacea and anti-inflammatory-dose doxycycline.

    PubMed

    Berman, Brian; Perez, Oliver A; Zell, Deborah

    2007-01-01

    Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of rosacea flares or for rosacea maintenance therapy, respectively, can lead to the development of antibiotic-resistant organisms. The first oral medication approved by the U.S. Food and Drug Administration for the treatment of rosacea in the United States is Oracea (CollaGenex Pharmaceuticals Inc., Newtown, PA, USA). Oracea is a 40 mg capsule of doxycycline monohydrate, containing 30 mg immediate-release and 10 mg delayed-release doxycycline beads ("anti-inflammatory-dose doxycycline"). Anti-inflammatory-dose doxycycline is not an antibiotic and does not lead to the development of antibiotic-resistant organisms. Each capsule of anti-inflammatory-dose doxycycline contains a total of 40 mg of anhydrous doxycycline as 30 mg of immediate-release and 10 mg of delayed-release beads. In contrast to other oral therapies, anti-inflammatory-dose doxycycline is taken once daily, which may increase treatment compliance. The results of two phase III trials have been encouraging, leading to the recent release (summer 2006) of Oracea for the treatment of rosacea in the United States. Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication). The risk of permanent teeth discoloration and decreased bone growth rate make anti-inflammatory-dose doxycycline contraindicated in infants and children. However, when used appropriately in patients with rosacea, anti-inflammatory-dose doxycycline may help prolong the effectiveness and life span of our most precious antibiotics.

  16. Anti-inflammatory Strategies to Prevent Diabetic Cardiovascular Disease.

    PubMed

    Jialal, I; Devaraj, S

    2015-08-01

    Diabetes is a proinflammatory state and inflammation is crucial in the genesis of vascular complications. While there are many anti-inflammatory strategies, most of which have been shown to reduce inflammation in diabetes, there is sparse data on reduction in cardiovascular events (CVEs). To date, the only anti-inflammatory strategies that have been shown to reduce CVE in diabetes include statins, angiotensin receptor blockers, metformin, and pioglitazone. We also discuss the role of novel emerging therapies.

  17. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins.

    PubMed

    Tubaro, Aurelia; Giangaspero, Anna; Sosa, Silvio; Negri, Roberto; Grassi, Gianpaolo; Casano, Salvatore; Della Loggia, Roberto; Appendino, Giovanni

    2010-10-01

    A selection of seven phytocannabinoids representative of the major structural types of classic cannabinoids and their corresponding cannabivarins was investigated for in vivo topical anti-inflammatory activity in the Croton oil mouse ear dermatitis assay. Differences in the terpenoid moiety were far more important for anti-inflammatory activity than those at the C-3 alkyl residue, suggesting the involvement not only of cannabinoid receptors, but also of other inflammatory end-points targeted by phytocannabinoids.

  18. Hypoglycemic agents and potential anti-inflammatory activity

    PubMed Central

    Kothari, Vishal; Galdo, John A; Mathews, Suresh T

    2016-01-01

    Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds. PMID:27114714

  19. Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics

    PubMed Central

    Perretti, Mauro; Dalli, Jesmond

    2009-01-01

    The appreciation that the inflammatory reaction does not ‘spontaneously’ finish, but rather that inflammatory resolution is an active phenomenon brought about by endogenous anti-inflammatory agonists opens multiple opportunities for a reassessment of the complexity of inflammation and its main mediators. This review dwells on one of these pathways, the one centred around the glucocorticoid-regulated protein Annexin A1 and its G protein-coupled receptor. In recent years, much of the knowledge detailing the processes by which Annexin A1 expresses its anti-inflammatory role on innate immunity has been produced. Moreover, the generation of the Annexin A1 null mouse colony has provided important proof-of-concept experiments demonstrating the inhibitory properties of this mediator in the context of inflammatory and/or tissue-injury models. Therefore, Annexin A1 acts as a pivotal homeostatic mediator, where if absent, inflammation would overshoot and be prolonged. This new understanding scientific information could guide us onto the exploitation of the biological properties of Annexin A1 and its receptor to instigate novel drug discovery programmes for anti-inflammatory therapeutics. This line of research relies on the assumption that anti-inflammatory drugs designed upon endogenous anti-inflammatory mediators would be burdened by a lower degree of secondary effects as these agonists would be mimicking specific pathways activated in our body for safe disposal of inflammation. We believe that the next few years will produce examples of such new drugs and the validity of this speculation could then be assessed. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:19845684

  20. Effect of etoricoxib, a cyclooxygenase-2 selective inhibitor on aberrant crypt formation and apoptosis in 1,2 dimethyl hydrazine induced colon carcinogenesis in rat model.

    PubMed

    Sharma, P; Kaur, J; Sanyal, S N

    2010-01-01

    Etoricoxib, a second generation selective cyclooxygenase-2 (COX-2) inhibitor had been studied for the chemopreventive response at its therapeutic anti-inflammatory dose in 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis in rat model. Eight to ten weeks old male rats of Sprague-Dawley strain were divided into four groups. While group 1 served as control and received the vehicle of the drugs, group 2 and 3 were administered freshly prepared DMH in 1mM EDTA-saline (pH 7.0) (30 mg/kg body wt/week, subcutaneously). Group 3 was also given a daily treatment of etoricoxib (0.6 mg/kg body wt orally) while the group 4 received the same amount of etoricoxib only, prepared in 0.5% carboxymethyl cellulose. Animals were sacrificed at the end of 6 weeks, body weight recorded and the colons were subjected to macroscopic and histopathological studies. The maximum number of raised mucosal lesions called the multiple plaque lesions (MPL) were found in the DMH group which significantly reverted back in the DMH + etoricoxib group, while very few MPLs were recorded in the control and etoricoxib only group. Similarly, the number of aberrant crypt foci (ACF), the point of future carcinogenic growth, was recorded more in the DMH group and significantly less in the DMH + etoricoxib group. The histopathological analysis showed the presence of severe hyperplasia, occasional dysplasia and aggregates of lymphoid cells in the localized regions. Etoricoxib group showed near normal histological features with the crypt architecture and the surrounding stromal tissue remaining intact. To ascertain the molecular mechanism of such anti-carcinogenic features the colonocytes were isolated and studied in primary culture for the evidence of apoptosis by fluorescent staining and genotoxic changes by single cell gel electrophoresis assay (comet assay) which shows that the DMH treated animals produced much less apoptotic nuclei but more comet producing cell, while these features were reverted back

  1. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

    SciTech Connect

    Choi, Solip; Nguyen, Van Thu; Tae, Nara; Lee, Suhyun; Ryoo, Sungwoo; Min, Byung-Sun; Lee, Jeong-Hyung

    2014-11-01

    Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE{sub 2}, butyl lucidenateD{sub 2} (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting the involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of these

  2. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac.

    PubMed

    Rattner, Barnett A; Whitehead, Maria A; Gasper, Grace; Meteyer, Carol U; Link, William A; Taggart, Mark A; Meharg, Andrew A; Pattee, Oliver H; Pain, Deborah J

    2008-11-01

    The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose -0.1-0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

  3. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac

    USGS Publications Warehouse

    Rattner, B.A.; Whitehead, M.A.; Gasper, G.; Meteyer, C.U.; Link, W.A.; Taggart, M.A.; Meharg, A.A.; Pattee, O.H.; Pain, D.J.

    2008-01-01

    The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose 0.1?0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

  4. Anti-Inflammatory Activity of Haskap Cultivars is Polyphenols-Dependent

    PubMed Central

    Rupasinghe, H. P. Vasantha; Boehm, Mannfred M. A.; Sekhon-Loodu, Satvir; Parmar, Indu; Bors, Bob; Jamieson, Andrew R.

    2015-01-01

    Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by lipopolysaccharide. Methanol extracts of haskap from different growing locations in Canada were prepared and characterized for their total phenolic profile using colorimetric assays and liquid chromatography—Mass spectrometry (UPLC-MS/MS). Human THP-1 monocytes were seeded in 24-well plates (5 × 105/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1 μg/mL) for 48 h to induce macrophage differentiation. After 48 h, the differentiated macrophages were washed with Hank’s buffer and treated with various concentrations of test compounds for 4 h, followed by the lipopolysaccharide (LPS)-stimulation (18 h). Borealis cultivar showed the highest phenolic content, flavonoid content and anthocyanin content (p < 0.05). A negative correlation existed between the polyphenol concentration of the extracts and pro-inflammatory cytokines: Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), prostaglandin (PGE2), and cyclooxygenase-2 (COX-2) enzyme. Borealis exhibited comparable anti-inflammatory effects to COX inhibitory drug, diclofenac. The results showed that haskap berry polyphenols has the potential to act as an effective inflammation inhibitor. PMID:26043379

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  7. Nonsteroidal Anti-Inflammatory Drugs for Wounds: Pain Relief or Excessive Scar Formation?

    PubMed Central

    Su, Wen-Hsiang; Cheng, Ming-Huei; Lee, Wen-Ling; Tsou, Tsung-Shan; Chang, Wen-Hsun; Chen, Chien-Sheng; Wang, Peng-Hui

    2010-01-01

    The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines—transforming growth factor-β (TGF-β) and prostaglandin E2 (PGE2)—are lipid mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-β and PGE2. PMID:20671960

  8. Newer, safer nonsteroidal anti-inflammatory drugs. Rational NSAID selection for arthritis.

    PubMed Central

    Bensen, W.; Zizzo, A.

    1998-01-01

    OBJECTIVE: To summarize current evidence that three new additions to nonsteroidal anti-inflammatory drugs (NSAIDs) offer comparable efficacy with fewer adverse effects than established NSAIDs. QUALITY OF EVIDENCE: No large randomized controlled trials (RCTs) have compared all important NSAIDs. Several RCTs have shown that H2 antagonists do not protect against NSAID side effects, but some RCTs compared the protective effect of misoprostol (Cytotec) used with other NSAIDs; others have compared etodolac (Ultradol) or nabumetone (Relafen) with placebo and naproxen (eg, Naprosyn). Postmarketing surveys have been used to support claims that the new NSAIDs have few gastric or renal side effects. MAIN FINDINGS: Using misoprostol in conjunction with traditional NSAIDs reduces gastric and renal adverse effects. Misoprostol can be taken at the same time as NSAIDs or in a combination tablet. Two new NSAIDS, etodolac and nabumetone, do not inhibit cyclooxygenase 1 prostaglandins, which occur in the stomach and kidneys, but more selectively block cyclooxygenase 2 prostaglandins, which cause arthritic inflammation. These two NSAIDs have efficacy profiles comparable to older NSAIDs but have markedly fewer side effects. CONCLUSIONS: Safer treatment for arthritis can be achieved by combining misoprostol with traditional NSAIDs or by using one of two new agents, nabumetone or etodolac. PMID:9481468

  9. Management of gastroduodenal ulcers caused by non-steroidal anti-inflammatory drugs.

    PubMed

    Hawkey, C J

    2000-02-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are a major cause of morbidity and mortality, probably resulting in the death of 1200 patients per annum in the UK. The main mechanism of toxicity involves an inhibition of prostaglandin synthesis that results in mucosal erosion as a result of the abrogation of defence mechanisms. However, acid peptic attack can deepen this initial injury. Thus, logical treatments include prostaglandin analogues as 'replacement therapy', acid suppression, enteric coating to avoid topical effects and the use of safer NSAIDs, including those that have little or no effect on gastric mucosal prostaglandin synthesis. There is less logic to the strategy of Helicobacter pylori (H. pylori) eradication, and the status of this approach is controversial. Overall, proton pump inhibitors have the best profile of efficacy and side-effects for the healing and prevention of NSAID-associated ulcers. Misoprostol is also effective and appears to be superior to proton pump inhibitors for superficial erosive injury. Early indications are that selective inhibitors of the inducible cyclooxygenase-2 enzyme have little or no effect in causing ulcers. Growing experience with these agents will probably revolutionize the management of patients with arthritic conditions. However, the increasing use of low-dose aspirin for cardiovascular prophylaxis means that gastroenterologists will have to continue to grapple with the problems of NSAID-associated ulcers for some time to come.

  10. 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.

  11. Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen).

    PubMed

    Gao, Hongwei; Sun, Wen; Zhao, Jianping; Wu, Xiaxia; Lu, Jin-Jian; Chen, Xiuping; Xu, Qiong-Ming; Khan, Ikhlas A; Yang, Shilin

    2016-09-26

    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.

  12. Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen)

    PubMed Central

    Gao, Hongwei; Sun, Wen; Zhao, Jianping; Wu, Xiaxia; Lu, Jin-Jian; Chen, Xiuping; Xu, Qiong-ming; Khan, Ikhlas A.; Yang, Shilin

    2016-01-01

    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. PMID:27666387

  13. Anti-Inflammatory Effect of Streptochlorin via TRIF-Dependent Signaling Pathways in Cellular and Mouse Models

    PubMed Central

    Shim, Do-Wan; Shin, Hee Jae; Han, Ji-Won; Shin, Woo-Young; Sun, Xiao; Shim, Eun-Jeong; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

    2015-01-01

    Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Streptochlorin attenuated the production of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1β, and IL-6 in LPS-stimulated RAW264.7 cells through inhibition of the Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling pathway. Furthermore, streptochlorin suppressed the infiltration of immune cells such as neutrophils into the lung and proinflammatory cytokine production such as IL-6 and TNF-α in broncho-alveolar lavage fluid (BALF) in the LPS-induced acute lung injury (ALI) mouse model. Streptochlorin has potent anti-inflammatory effects through regulating TRIF-dependent signaling pathways, suggesting that streptochlorin may provide a valuable therapeutic strategy in treating various inflammatory diseases. PMID:25822875

  14. Anti-Inflammatory Effect of Rosa rugosa Flower Extract in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

    PubMed Central

    Tursun, Xirali; Zhao, Yongxin; Talat, Zulfiya; Xin, Xuelei; AdilaTursun; Abdulla, Rahima; AkberAisa, Haji

    2016-01-01

    Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-a, interleukin (IL)-6, and interleukin 1β (IL-1β), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-κB) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders. PMID:26797110

  15. Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis

    PubMed Central

    Liu, Shu-Ling; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Lin, Wang-Ching; Liao, Jung-Chun; Huang, Guan-Jhong

    2012-01-01

    Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products. PMID:22778769

  16. Leonurine exerts anti-inflammatory effect by regulating inflammatory signaling pathways and cytokines in LPS-induced mouse mastitis.

    PubMed

    Song, Xiaojing; Wang, Tiancheng; Zhang, Zecai; Jiang, Haichao; Wang, Wei; Cao, Yongguo; Zhang, Naisheng

    2015-02-01

    Bovine mastitis is defined as the inflammation of mammary gland and is the most multiple diseases in dairy cattle. There is still no effective treatment now. Leonurine, extracted from Leonurus cardiaca, has been proved to have anti-inflammatory effect. In the present study, we utilized a mouse mastitis model to study the effect of leonurine on LPS-induced mastitis. Leonurine was administered three times during the 24 h after inducing infection in the mammary gland. The results showed that leonurine significantly alleviated LPS-induced histopathological changes, downregulated the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), upregulated the level of anti-inflammatory cytokine interleukin-10 (IL-10), and inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further study revealed that leonurine inhibited the expression of Toll-like receptor 4 (TLR4) and the activation of nuclear factor-kappaB (NF-κB) and the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK). Therefore, the results demonstrated that leonurine could downregulate the expression of TNF-α, IL-6, iNOS, and COX-2 and upregulate the expression of IL-10 mainly by inhibiting the expression of TLR4 and the activation of NF-κB and the phosphorylation of p38, ERK, and JNK. Leonurine may be a potential agent for mastitis therapy.

  17. Resveratrol nanoparticle system improves dissolution properties and enhances the hepatoprotective effect of resveratrol through antioxidant and anti-inflammatory pathways.

    PubMed

    Lee, Chiang-Wen; Yen, Feng-Lin; Huang, Haw-Wei; Wu, Tzu-Hui; Ko, Horng-Huey; Tzeng, Wen-Sheng; Lin, Chun-Ching

    2012-05-09

    Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection. Unfortunately, RES is restricted in clinical application due to poor dissolution property and adsorption. In addition, red wine as a supplement for preventing disease is not recommended for patients with alcohol-related disorders. To address these limitations, we successfully developed a novel RES nanoparticle system (RESN) and demonstrated that RESN could circumvent the physicochemical drawbacks of raw RES with respect to dissolution, such as the reduction of particle size, amorphous transformation, and hydrogen-bond formation. In addition, we employed an animal model of CCl₄-induced hepatotoxicity to estimate the potential of the nanoparticle formulation to improve the hepatoprotective effect of orally administered RES. Our results demonstrated that RESN can diminish liver function markers (aspartate aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due to CCl₄-induced hepatotoxicity in rats, when compared with RES administration. The effect was achieved by reducing oxidative stress (decreased reactive oxygen species and lipid peroxidation) and lowering inflammatory cytokines (decreased tumor necrosis factor-α and interleukin 1β) and protein expression (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2, and caspase-3). In conclusion, enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases.

  18. Anti-inflammatory effects of an ethanolic extract of guava (Psidium guajava L.) leaves in vitro and in vivo.

    PubMed

    Jang, Mi; Jeong, Seung-Weon; Cho, Somi K; Ahn, Kwang Seok; Lee, Jong Hyun; Yang, Deok Chun; Kim, Jong-Chan

    2014-06-01

    Plant extracts have been used as a source of medicines for a wide variety of human ailments. Among the numerous traditional medicinal herbs, Psidium guajava L. (Myrtaceae), commonly known as guava, has long been used in folk medicines as a therapeutic agent for the treatment of numerous diseases in East Asian and other countries. The aim of this study was to investigate the anti-inflammatory activity of an ethanolic leaf extract of P. guajava (guava) in vitro and in vivo. Our results demonstrated that guava leaf extract (GLE) significantly inhibited lipopolysaccharide (LPS)-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner. GLE suppressed the expression and activity of both inducible nitric oxide synthase and cyclooxygenase-2 in part through the downregulation of ERK1/2 activation in RAW264.7 macrophages. Furthermore, GLE exhibited significant anti-inflammatory activity in 2 different animal models-Freund's complete adjuvant-induced hyperalgesia in the rat and LPS-induced endotoxic shock in mice.

  19. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells.

    PubMed

    Choi, Solip; Nguyen, Van Thu; Tae, Nara; Lee, Suhyun; Ryoo, Sungwoo; Min, Byung-Sun; Lee, Jeong-Hyung

    2014-11-01

    Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE2, butyl lucidenateD2 (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting the involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum.

  20. In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus.

    PubMed

    Park, Young-Mi; Won, Jong-Heon; Kim, Yang-Hee; Choi, Jong-Won; Park, Hee-Juhn; Lee, Kyung-Tae

    2005-10-03

    The mushroom Inonotus obliquus (Fr.) Pilát (Hymenochaetaceae), has been traditionally used for the treatment of gastrointestinal cancer, cardiovascular disease and diabetes in Russia, Poland and most of Baltic countries. This study was designed to investigate the anti-inflammatory and anti-nociceptive effects of the methanol extract from Inonotus obliquus (MEIO) in vivo and in vitro. MEIO (100 or 200 mg/(kgday), p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activity, as determined by an acetic acid-induced abdominal constriction test and a hot plate test in mice. To reveal the mechanism of the anti-inflammatory effect of MEIO, we examined its effect on lipopolysaccharide (LPS)-induced responses in a murine macrophage cell line RAW 264.7. MEIO was found to significantly inhibit the productions of nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. Consistent with these observations, MEIO potently inhibited the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, MEIO inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB), and this was associated with the prevention of inhibitor kappaB degradation and a reduction in nuclear p65 protein levels. Taken together, our data indicate that the anti-inflammatory and anti-nociceptive properties of MEIO may be due to the inhibition of iNOS and COX-2 expression via the down-regulation of NF-kappaB binding activity.

  1. Evidence for anti-inflammatory and antioxidative properties of dried plum polyphenols in macrophage RAW 264.7 cells.

    PubMed

    Hooshmand, Shirin; Kumar, Ajay; Zhang, Ji Yao; Johnson, Sarah A; Chai, Sheau C; Arjmandi, Bahram H

    2015-05-01

    This study presents the anti-inflammatory and antioxidative properties of dried plum (Prunus domestica L.) polyphenols in macrophage RAW 264.7 cells. We hypothesized that dried plum polyphenols have strong anti-inflammatory and antioxidant properties against lipopolysaccharide (LPS)-induced production of the pro-inflammatory markers, nitric oxide (NO) and cyclooxygenase-2 (COX-2), and the lipid peroxidation product, malondialdehyde, in activated macrophage RAW 264.7 cells. To test this hypothesis, macrophage RAW 264.7 cells were stimulated with either 1 μg ml(-1) (for measurement of NO production) or 1 ng ml(-1) (for measurement of COX-2 expression) of LPS to induce inflammation and were treated with different doses of dried plum polyphenols (0.0, 0.1, 1, 10, 100 and 1000 μg ml(-1)). Dried plum polyphenols at a dose of 1000 μg ml(-1) was able to significantly (P < 0.05) reduce NO production by 43%. Additionally, LPS-induced expression of COX-2 was significantly (P < 0.05) reduced by 100 and 1000 μg ml(-1) dried plum polyphenols. To investigate the antioxidant activity of dried plum polyphenols, macrophage RAW 264.7 cells were stimulated with 100 μg ml(-1) of FeSO4 + 1 mM ml(-1) of H2O2 to induce lipid peroxidation. Dried plum polyphenols at a dose of 1000 μg ml(-1) showed a 32% reduction in malondialdehyde production. These findings indicate that dried plum polyphenols are potent anti-inflammatory and antioxidative agents in vitro.

  2. The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: Structure-activity relationships of flavones.

    PubMed

    During, Alexandrine; Larondelle, Yvan

    2013-12-15

    The aim of this study was to investigate whether methoxylated flavones versus their unmethylated analogs can modulate the intestinal inflammatory response. Flavone effects were assessed on soluble pro-inflammatory mediator (IL-8, IL-6, macrophage chemoattractant protein-1 (MCP-1), and cyclooxygenase-2 (COX-2)-derived PGE2) production and on nuclear factor (NF)-κB activation in 3d-confluent and 21d-differentiated Caco-2 cells stimulated with interleukin (IL)-1β. Chrysin (CHRY) showed anti-inflammatory properties by decreasing COX-2-derived PGE2 and reducing NF-κB activation. Compared to CHRY, the dimethoxylated form (CHRY-DM) significantly reduced the secretion of all pro-inflammatory mediators, except IL-8, at both cellular stages (P<0.05); these effects being dose-dependent in 3d-cells. The reduction of NF-κB activation was significantly more pronounced with CHRY-DM. By evaluating other flavones, it was established that several structural dispositions of flavones seemed to be determinant in order to attenuate the intestinal inflammatory response, such as methoxylation of the 5- and 7-hydroxyl groups on the A-ring, non-methoxylation of the 3'-hydroxyl groups on the B-ring, and methoxylation of the 3-hydroxyl group on the C-ring. Of all flavones examined, CHRY-DM exhibited the strongest anti-inflammatory activity. These data indicate that, in the Caco-2 cell model, methoxylation of CHRY greatly improves its anti-inflammatory properties, probably through a more pronounced inhibition of the NF-κB signaling pathway. Nevertheless, methoxylation of other flavones was not systematically beneficial.

  3. Anti-inflammatory potential of peat moss extracts in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    PubMed

    Choi, Woo-Suk; Jeong, Jin-Woo; Kim, Sung Ok; Kim, Gi-Young; Kim, Byung-Woo; Kim, Cheol Min; Seo, Yong-Bae; Kim, Woe-Yeon; Lee, Sang-Yeol; Jo, Kwon-Ho; Choi, Young Ju; Choi, Yung Hyun; Kim, Gun-Do

    2014-10-01

    The aim of the present study was to identify the anti-inflammatory and anti-oxidative effects of peat moss aqueous extract (PME) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. To demonstrate the anti-inflammatory and antioxidant effects of PME, the levels of nitric oxide (NO) and cytokines were measured using Griess reagent and cytokine ELISA kits, respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis were conducted to evaluate the expression of genes and proteins. Immunofluorescence was used to measure the expression and translocation of transcription factors. Pre-treatment with PME inhibited the production of prostaglandin E(2) and NO by suppressing the gene expression of cyclooxygenase-2 and inducible NO synthase, respectively. The LPS-stimulated gene expression and the production of tumor necrosis factor-α and interleukin-1β were significantly reduced by PME. In the LPS-stimulated RAW 264.7 cells, nuclear factor‑κB (NF-κB) translocated from the cytosol to the nucleus, while pre-treatment with PME induced the sequestration of NF-κB in the cytosol through the inhibition of IκBα degradation. In the same manner, PME contributed to the inhibition of the activation of mitogen-activated protein kinases. In addition, the PME-treated RAW 264.7 cells facilitated the activation of nuclear factor-like 2 (Nrf2) , and in turn, enhanced heme oxygenase-1 (HO-1) expression. These results indicate that PME exerts anti-inflammatory and antioxidant effects, and suggest that PME may neutralize inflammation and prevent cellular damage by oxidative stress.

  4. Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

    PubMed Central

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender

    2016-01-01

    Objective: Berberis aristata (Berberidaceae) is an important medicinal plant used in traditional system of medicine for the treatment of rheumatoid arthritis and other inflammatory disorders. The aim of the present study is to scientifically validate the traditional use of BA in the treatment of inflammatory disorders. Materials and Methods: Anti-inflammatory and anti-granuloma activity of BA hydroalcoholic extract (BAHE) were evaluated in experimental models, viz., carrageenan-induced paw edema, cotton pellet-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Expression of inflammatory mediators, viz., tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, TNF-R1, and cyclooxygenase-2 (COX-2) was carried out in serum and peritoneal macrophages to derive the plausible mechanism of BAHE in activated peritoneal macrophages. Results: Pretreatment with BAHE produced a dose-dependent reduction (P < 0.01) in carrageenan-induced paw edema and cotton pellet-induced granuloma model. BAHE treatment produced significant (P < 0.01) reduction in serum inflammatory cytokine levels as compared to control. Protein expression of pro-inflammatory markers, IL-1β, IL-6, TNF-R1, and COX-2, was found to be reduced in stimulated macrophages whereas anti-inflammatory cytokine, IL-10, was upregulated in peritoneal macrophages. Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators. PMID:27114638

  5. Evaluation of the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages.

    PubMed

    Gill, Sharonjit K; Marriott, Helen M; Suvarna, S Kim; Peachell, Peter T

    2016-12-15

    The principal mechanism by which bronchodilator β-adrenoceptor agonists act is to relax airways smooth muscle although they may also be anti-inflammatory. However, the extent of anti-inflammatory activity and the cell types affected by these agonists are uncertain. The purpose of this study was to evaluate whether β-adrenoceptor agonists prevent pro-inflammatory cytokine generation from activated human lung macrophages. Macrophages were isolated and purified from human lung. The cells were pre-treated with both short-acting (isoprenaline, salbutamol, terbutaline) and long-acting (formoterol, salmeterol, indacaterol) β-agonists before activation with lipopolysaccharide (LPS) to induce cytokine (TNFα, IL-6, IL-8 and IL-10) generation. The experiments showed that short-acting β-agonists were poor inhibitors of cytokine generation. Of the long-acting β-agonists studied, formoterol was also a weak inhibitor of cytokine generation whereas only indacaterol and salmeterol showed moderate inhibitory activity. Further experiments using the β2-adrenoceptor antagonist ICI-118,551 suggested that the effects of indacaterol were likely to be mediated by β2-adrenoceptors whereas those of salmeterol were not. These findings were corroborated by functional desensitization studies in which the inhibitory effects of indacaterol appeared to be receptor-mediated whereas those of salmeterol were not. Taken together, the data indicate that the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages are modest.

  6. Cannabinoid-like anti-inflammatory compounds from flax fiber.

    PubMed

    Styrczewska, Monika; Kulma, Anna; Ratajczak, Katarzyna; Amarowicz, Ryszard; Szopa, Jan

    2012-09-01

    Flax is a valuable source of fibers, linseed and oil. The compounds of the latter two products have already been widely examined and have been proven to possess many health-beneficial properties. In the course of analysis of fibers extract from previously generated transgenic plants overproducing phenylpropanoids a new terpenoid compound was discovered.The UV spectra and the retention time in UPLC analysis of this new compound reveal similarity to a cannabinoid-like compound, probably cannabidiol (CBD). This was confirmed by finding two ions at m/z 174.1 and 231.2 in mass spectra analysis. Further confirmation of the nature of the compound was based on a biological activity assay. It was found that the compound affects the expression of genes involved in inflammatory processes in mouse and human fibroblasts and likely the CBD from Cannabis sativa activates the specific peripheral cannabinoid receptor 2 (CB2) gene expression. Besides fibers, the compound was also found in all other flax tissues. It should be pointed out that the industrial process of fabric production does not affect CBD activity.The presented data suggest for the first time that flax products can be a source of biologically active cannabinoid-like compounds that are able to influence the cell immunological response. These findings might open up many new applications for medical flax products, especially for the fabric as a material for wound dressing with anti-inflammatory properties.

  7. 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.

  8. Anti-inflammatory role of obestatin in autoimmune myocarditis.

    PubMed

    Pamukcu, Ozge; Baykan, Ali; Bayram, Latife Cakir; Narin, Figen; Cetin, Nazmi; Narin, Nazmi; Argun, Mustafa; Ozyurt, Abdullah; Uzum, Kazim

    2016-01-01

    Obestatin is a popular endogeneous peptide, known to have an autoimmune regulatory effect on energy metabolism and the gastrointestinal system. Studies regarding the anti-inflammatory effects of obestatin are scarce. The aim of this study was to show the anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with subcutaneous administration of porcine cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with obestatin (50 μg/kg) was started before the induction of myocarditis and continued for 3 weeks. The severity of myocarditis was evidenced by clinical, echocardiographic and histological findings. In addition, by-products of neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory cytokines were measured in serum. Obestatin significantly ameliorated the clinical and histopathological severity of autoimmune myocarditis. Therapeutic effects of obestatin in myocarditis were associated with reduced lipid peroxidation, suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis, inhibition of serum inflammatory and activation of anti-inflammatory cytokines. Histopathologically, the left ventricle was significantly dilated, and its wall thickened, along with widespread lymphocytic and histocytic infiltration. The myocardium was severely infiltrated with relatively large mononuclear cells. These histopathological changes were observed in lesser degrees in obestatin-treated rats. This study demonstrated a novel anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis. Consequently, obestatin administration may represent a promising therapeutic approach for myocarditis and dilated cardiomyopathy in the future.

  9. C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    PubMed

    Reddy, Madhava C; Subhashini, J; Mahipal, S V K; Bhat, Vadiraja B; Srinivas Reddy, P; Kiranmai, G; Madyastha, K M; Reddanna, P

    2003-05-02

    C-Phycocyanin (C-PC) is one of the major biliproteins of Spirulina platensis, a blue green algae, with antioxidant and radical scavenging properties. It is also known to exhibit anti-inflammatory and anti-cancer properties. However, the mechanism of action of C-PC is not clearly understood. Previously, we have shown that C-PC selectively inhibits cyclooxygenase-2 (COX-2), an inducible isoform that is upregulated during inflammation and cancer. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of C-PC on LPS stimulated RAW 264.7 mouse macrophage cell line. These studies have shown a dose dependent reduction in the growth and multiplication of macrophage cell line by C-PC. This decrease in cell number appears to be mediated by C-PC induced apoptosis as evidenced by flow cytometric and confocal microscopic studies. Cells treated with 20 micro M C-PC showed typical nuclear condensation and 16.6% of cells in sub-G(o)/G(1) phase. These cells also showed DNA fragmentation in a dose dependent manner. The studies on poly(ADP ribose) polymerase (PARP) cleavage showed typical fragmentation pattern in C-PC treated cells. This C-PC induced apoptosis in RAW 264.7 cells appears to be mediated by the release of cytochrome c from mitochondria and independent of Bcl-2 expression. These effects of C-PC on RAW 264.7 cells may be due to reduced PGE(2) levels as a result of COX-2 inhibition.

  10. Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis.

    PubMed

    Shao, Yun; Sun, Kun; Xu, Wei; Li, Xiao-Lin; Shen, Hong; Sun, Wei-Hao

    2014-09-28

    Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.

  11. Extract from Nandina domestica inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in human pulmonary epithelial A549 cells.

    PubMed

    Ueki, Takuro; Akaishi, Tatsuhiro; Okumura, Hidenobu; Abe, Kazuho

    2012-01-01

    Extract from fruits of Nandina domestica THUNBERG (NDE) has been used to improve cough and breathing difficulty in Japan for many years. To explore whether NDE may alleviate respiratory inflammation, we investigated its effect on expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E₂ (PGE₂) in human pulmonary epithelial A549 cells in culture. Treatment with lipopolysaccharide (LPS; 6 µg/mL) resulted in an increase of COX-2 expression and PGE₂ production in A549 cells. Both the LPS-induced COX-2 expression and PGE₂ production were significantly inhibited by NDE (1-10 µg/mL) in a concentration-dependent manner. NDE did not affect COX-1 expression nor COX activity. These results suggest that NDE downregulates LPS-induced COX-2 expression and inhibits PGE₂ production in pulmonary epithelial cells. Furthermore, higenamine and nantenine, two major constituents responsible for tracheal relaxing effect of NDE, did not mimic the inhibitory effect of NDE on LPS-induced COX-2 expression in A549 cells. To identify active constituent(s) of NDE responsible for the anti-inflammatory effect, NDE was introduced in a polyaromatic absorbent resin column and stepwise eluted to yield water fraction, 20% methanol fraction, 40% methanol fraction, 99.8% methanol fraction, and 99.5% acetone fraction. However, none of these five fractions alone inhibited LPS-induced COX-2 expression. On the other hand, exclusion of water fraction from NDE abolished the inhibitory effect of NDE on LPS-induced COX-2 expression. These results suggest that constituent(s) present in water fraction is required but not sufficient for the anti-inflammatory activity of NDE, which may result from interactions among multiple constituents.

  12. Anti-inflammatory Flavonoids Isolated from Passiflora foetida.

    PubMed

    Nguyen, Thi Yen; To, Dao Cuong; Tran, Manh Hung; Lee, Joo Sang; Lee, Jeong Hyung; Kim, Jeong Ah; Woo, Mi Hee; Min, Byung Sun

    2015-06-01

    In this study, we evaluated the anti-inflammatory activity of the soluble ethyl acetate fraction and chemical components of the stem bark of Passiflora foetida (Passifloraceae). Ten flavonoids (1-10) were isolated by various chromatographic techniques, and their structures were determined based on spectroscopic analyses by using nuclear magnetic resonance (NMR). Luteolin (2) and chrysoeriol (3) showed the most potent inhibition of nitric oxide (NO) production in macrophage cell line, RAW264.7, with half maximal inhibitor concentration (IC50) values of 1.2 and 3.1 μM, respectively. These compounds suppressed lipopolysaccharide (LPS)-induced inducible NO synthase (iNOS) expression at the transcription level. Our research indicates that the stem bark of P. foetida has significant anti-inflammatory properties, suggesting that its flavonoids may have anti-inflammatory benefits.

  13. Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

    PubMed Central

    Yen, Chiao-Ting; Nakagawa-Goto, Kyoko; Hwang, Tsong-Long; Morris-Natschke, Susan L.; Bastow, Kenneth F.; Wu, Yang-Chang; Lee, Kuo-Hsiung

    2012-01-01

    Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC50 values of 0.9 and 0.8 μ g/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control. PMID:22595179

  14. Increased temperature and entropy production in cancer: the role of anti-inflammatory drugs.

    PubMed

    Pitt, Michael A

    2015-02-01

    Some cancers have been shown to have a higher temperature than surrounding normal tissue. This higher temperature is due to heat generated internally in the cancer. The higher temperature of cancer (compared to surrounding tissue) enables a thermodynamic analysis to be carried out. Here I show that there is increased entropy production in cancer compared with surrounding tissue. This is termed excess entropy production. The excess entropy production is expressed in terms of heat flow from the cancer to surrounding tissue and enzymic reactions in the cancer and surrounding tissue. The excess entropy production in cancer drives it away from the stationary state that is characterised by minimum entropy production. Treatments that reduce inflammation (and therefore temperature) should drive a cancer towards the stationary state. Anti-inflammatory agents, such as aspirin, other non-steroidal anti-inflammatory drugs, corticosteroids and also thyroxine analogues have been shown (using various criteria) to reduce the progress of cancer.

  15. Anti-inflammatory effects of apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway.

    PubMed

    Wang, Jing; Liu, Yu-Tao; Xiao, Lu; Zhu, Lingpeng; Wang, Qiujuan; Yan, Tianhua

    2014-12-01

    This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of apigenin lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. In this study, the anti-inflammatory effects of apigenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with apigenin prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio in total leukocyte number and neutrophil percent in the bronchoalveolar lavage fluid (BALF) and in IL-6 and IL-1β, the tumor neurosis factor-α (TNF-α) in the BALF. These results showed that anti-inflammatory effects of apigenin against the LPS-induced ALI may be due to its ability of primary inhibition of cyclooxygenase-2 (COX-2) gene expression and nuclear factor kB (NF-kB) gene expression of lung. The results presented here suggest that the protective mechanism of apigenin may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of COX-2 and NF-kB activation. The results support that use of apigenin is beneficial in the treatment of ALI.

  16. Leaves of Raphanus sativus L. Shows Anti-Inflammatory Activity in LPS-Stimulated Macrophages via Suppression of COX-2 and iNOS Expression

    PubMed Central

    Park, Hye-Jin; Song, Minjung

    2017-01-01

    Raphanus sativus L. (RS) is a cruciferous vegetable that is widely consumed in Korea. The anticancer activity of leaves of RS (RSL) extract has been investigated; however, no studies focused on its anti-inflammatory effects. Therefore, the aim of the current study was to evaluate the anti-inflammatory effects of RSL extract. In brief, RSL powder was fractionated into n-hexane, chloroform, ethyl acetate, n-butanol, and water-soluble fractions. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with each fraction for initial screening. It was found that the chloroform fraction significantly inhibited nitric oxide release in LPS-stimulated RAW264.7 cells with a half maximal inhibitory concentration value of 196 μg/mL. In addition, the mRNA and protein expression levels of inducible nitric oxide synthase, measured using reverse transcriptase-polymerase chain reaction and western blotting, respectively, were reduced in a concentration-dependent manner. Moreover, the inflammatory cyclooxygenase-2 enzyme expression decreased. Furthermore, the expression of nuclear factor-kappa B (NF-κB), the key regulator of the transcriptional activation of the inflammatory cytokine genes, was reduced by the RSL chloroform fraction. Therefore, the results of our study suggest that RSL exhibits anti-inflammatory effects in LPS-stimulated macrophages via NF-κB inactivation.

  17. Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis.

    PubMed

    Liu, Y-W; Ong, W-K; Su, Y-W; Hsu, C-C; Cheng, T-H; Tsai, Y-C

    2016-06-01

    Lactic acid bacteria (LAB) with anti-inflammatory effects may be beneficial to the prevention or treatment for inflammation-related diseases, such as inflammatory bowel diseases. In an in vitro assay, heat-killed Lactobacillus brevis K65 (K65) reduced lipopolysaccharide-induced production of nitric oxide, tumour necrosis factor (TNF)-α and prostaglandin E2 in RAW 264.7 cells. In RAW 264.7 cells stably expressing an ind=ucible nitric oxide synthase (iNOS) reporter, viable K65 showed greater inhibition of iNOS production than its heat-killed form. In order to further examine the in vivo anti-inflammatory effect of K65, viable K65 was orally administered to BALB/c mice before and during the period of dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). K65 improved UC symptoms, including reduced the levels of the pro-inflammatory cytokines, TNF-α, interleukin (IL)-6 and IL-1β, and lowered the activity of myeloperoxidase. Furthermore, K65 inhibited TNF-α, cyclo-oxygenase 2, forkhead box P3, and Toll-like receptor 4 mRNA expression in the colonic tissue of DSS-induced UC mice. Taken together, K65, a LAB with in vitro anti-inflammatory activity showed preventive effects on mice with DSS-induced UC by lowering the expression of inflammatory molecules.

  18. Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-α gene by the same.

    PubMed

    Subramoniam, Appian; Asha, Velikkakathu V; Nair, Sadasivan Ajikumaran; Sasidharan, Sreejith P; Sureshkumar, Parameswaran K; Rajendran, Krishnan Nair; Karunagaran, Devarajan; Ramalingam, Krishnan

    2012-06-01

    In view of the folklore use of green leaves to treat inflammation, the anti-inflammatory property of chlorophylls and their degradation products were studied. Chlorophyll a and pheophytin a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll a inhibited bacterial lipopolysaccharide-induced TNF-α (a pro-inflammatory cytokine) gene expression in HEK293 cells, but it did not influence the expression of inducible nitric acid synthase and cyclooxygenase-2 genes. Chlorophyll b only marginally inhibited both inflammation and TNF-α gene expression. But both chlorophyll a and chlorophyll b showed the same level of marginal inhibition on 12-O-tetradecanoyl-phorbol-13-acetate-induced NF-κB activation. Chlorophylls and pheophytins showed in vitro anti-oxidant activity. The study shows that chlorophyll a and its degradation products are valuable and abundantly available anti-inflammatory agents and promising for the development of phytomedicine or conventional medicine to treat inflammation and related diseases.

  19. Anti-inflammatory activity of n-propyl gallate through down-regulation of NF-κB and JNK pathways.

    PubMed

    Jung, Hyun-Joo; Kim, Su-Jung; Jeon, Woo-Kwang; Kim, Byung-Chul; Ahn, Kisup; Kim, Kyunghoon; Kim, Young-Myeong; Park, Eun-Hee; Lim, Chang-Jin

    2011-10-01

    The present study aimed to assess anti-inflammatory activity and underlying mechanism of n-propyl gallate, the n-propyl ester of gallic acid. n-Propyl gallate was shown to contain anti-inflammatory activity using two experimental animal models, acetic acid-induced permeability model in mice, and air pouch model in rats. It suppressed production of nitric oxide and induction of inducible nitric oxide synthase and cyclooxygenase-2 in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. It was able to diminish reactive oxygen species level elevated in the LPS-stimulated RAW264.7 macrophage cells. It also suppressed gelatinolytic activity of matrix metalloproteinase-9 enhanced in the LPS-stimulated RAW264.7 macrophage cells. It inhibited inhibitory κB-α degradation and enhanced NF-κB promoter activity in the stimulated macrophage cells. It was able to suppress phosphorylation of c-Jun NH(2)-terminal kinase 1/2 (JNK1/2) and activation of c-Jun promoter activity in the stimulated macrophage cells. In brief, n-propyl gallate possesses anti-inflammatory activity via down-regulation of NF-κB and JNK pathways.

  20. Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs of Garcinia esculenta on Stimulated Macrophage.

    PubMed

    Zhang, Dan-Dan; Zhang, Hong; Lao, Yuan-zhi; Wu, Rong; Xu, Jin-wen; Murad, Ferid; Bian, Ka; Xu, Hong-Xi

    2015-01-01

    Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE's capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases.

  1. Observing Anti-inflammatory and Anti-nociceptive Activities of Glycyrrhizin Through Regulating COX-2 and Pro-inflammatory Cytokines Expressions in Mice.

    PubMed

    Wang, Hong-Ling; Li, Yu-Xiang; Niu, Ya-Ting; Zheng, Jie; Wu, Jing; Shi, Guang-Jiang; Ma, Lin; Niu, Yang; Sun, Tao; Yu, Jian-Qiang

    2015-12-01

    The present study aimed to investigate the potential anti-inflammatory and anti-nociceptive activities of glycyrrhizin (GL) in mice and to explore the possible related mechanisms. Xylene-induced ear edema, carrageenan-induced paw edema and acetic acid-induced vascular permeability test were used to investigate the anti-inflammatory activities of GL in mice. Anti-nociceptive effects of GL were assessed by using acetic acid-induced writhing, hot plate test and formalin test, as well as evaluation of spontaneous locomotor activity and motor performance. The mRNA expression of pro-inflammatory cytokines (such as TNF-α, IL-6 and iNOS) and the protein expression of cyclooxygenase-2 (COX-2) were explored by using real-time fluorogenic PCR and Western blot, respectively. The results showed that GL significantly reduced xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeation. Additionally, GL significantly inhibited the nociceptions induced by acetic acid and formalin. However, the nociceptions could not be decreased by GL in the hot plate test, and GL did not affect spontaneous locomotor activity and motor performance. The expression levels of TNF-α, IL-6, iNOS and COX-2 were significantly downregulated by GL. In conclusion, GL exerts significant anti-inflammatory and analgesic activities by attenuating the expression levels of TNF-α, IL-6, iNOS and COX-2.

  2. Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs of Garcinia esculenta on Stimulated Macrophage

    PubMed Central

    Zhang, Dan-Dan; Zhang, Hong; Lao, Yuan-zhi; Wu, Rong; Xu, Jin-wen; Murad, Ferid; Bian, Ka; Xu, Hong-Xi

    2015-01-01

    Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of NO and PGE2 during inflammation progress. Additionally, TIE also suppressed the expression of inflammatory cytokines IL-6, IL-12, and TNF-α. TIE-led suppression in iNOS, COX-2, and cytokines production were probably the consequence of TIE's capability to block ERK and p38MAPK signaling pathway. Moreover, TIE blocked activation of nuclear factor-kappa B (NF-κB) as well as NF-κB regulation of miR155 expression. Our study suggests that TIE may represent as a potential therapeutic agent for the treatment of inflammatory diseases. PMID:26538826

  3. 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.

  4. Dietary flavonoids: molecular mechanisms of action as anti- inflammatory agents.

    PubMed

    Marzocchella, Laura; Fantini, Massimo; Benvenuto, Monica; Masuelli, Laura; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto

    2011-09-01

    Flavonoids are a large group of polyphenolic compounds, which are ubiquitously expressed in plants. They are grouped according to their chemical structure and function into flavonols, flavones, flavan-3-ols, anthocyanins, flavanones and isoflavones. Many of flavonoids are found in fruits, vegetables and beverages. Flavonoids have been demonstrated to have advantageous effects on human health because their anti-allergic, anti-inflammatory, anti-platelet aggregation, anti-tumor and anti-oxidant behavior. This report reviews the current knowledge on the molecular mechanisms of action of flavonoids as anti-inflammatory agents and also discusses the relevant patents.

  5. Anti-inflammatory new coumarin from the Ammi majus L

    PubMed Central

    2012-01-01

    Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L. led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6-hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated from this plant. The structures of the compounds (2 &3) were elucidated by spectroscopic data interpretation and showed anti-inflammatory and anti-viral activity. Graphical abstract An efficient, one-new coumarin (2) was isolated from the aerial parts of the A. Majus L. was evaluated for their anti-viral and anti-inflammatory activities. PMID:22373472

  6. Nonsteroidal Anti-inflammatory Drug Use in Horses.

    PubMed

    Knych, Heather K

    2017-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic agents and are arguably the most commonly used class of drugs in equine medicine. This article provides a brief review of the mechanism of action, therapeutic uses, pharmacokinetics, and adverse effects associated with their use in horses. The use of COX-2 selective NSAIDs in veterinary medicine has increased over the past several years and special emphasis is given to the use of these drugs in horses. A brief discussion of the use of NSAIDs in performance horses is also included.

  7. New anti-inflammatory flavonoids from Cadaba glandulosa Forssk.

    PubMed

    Mohamed, Gamal A; Ibrahim, Sabrin R M; Al-Musayeib, Nawal M; Ross, Samir A

    2014-04-01

    Three new flavonoids; kaempferol-4'-phenoxy-3,3',5'-trimethylether (3), rhamnocitrin-4'-(4-hydroxy-3-methoxy)phenoxy-3-methyl ether (4), and rhamnocitrin-3-O-neohesperoside-4'-O-rhamnoside (6), along with three known compounds; 4-methoxy-benzyldehyde (1), kaempferol-3-methylether (2), and stachydrine (5) were isolated from the aerial parts of Cadaba glandulosa Forssk. Their chemical structures were established by physical, chemical, and spectral methods, as well as comparison with literature data. The antioxidant and anti-inflammatory activities of the isolated compounds were determined. Compounds 2-4, and 6 exhibited potent anti-inflammatory activity comparable with indomethacin and moderate antioxidant activity.

  8. Structural basis of the anti-inflammatory activity of quercetin: inhibition of the 5-hydroxytryptamine type 2 receptor.

    PubMed

    Rotelli, Alejandra Ester; Aguilar, Carlos Fernando; Pelzer, Lilian Eugenia

    2009-09-01

    The anti-inflammatory activity of quercetin was evaluated through serotonin-induced rat-paw edema. The experiments showed that quercetin had an important effect on acute inflammatory processes. Docking of serotonin and quercetin into the homology model of the 5-Hydroxytryptamine Type 2 Receptor allowed to analyze the structural basis of the anti-inflammatory activity. Results showed that serotonin and quercetin bind in the same region of the active site with a similar binding energy but quercetin has a much bigger inhibition constant. Therefore, it seems possible that quercetin may act as a natural inhibitor of the receptor blocking the acute inflammation generated by serotonin.

  9. 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

  10. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    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.

  11. [Helicobacter pylori, nonsteroidal anti-inflammatory agents and gastroduodenal changes].

    PubMed

    Teixeira, A V

    1995-09-01

    The author discusses the possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) which may play an important role in the unleashing of gastroduodenal lesions. To our knowledge, AINEs have no influence on the prevalence of infection by Hp and the latter does not seem to influence the development and intensity of the lesions caused by NSAIDs.

  12. Anti-inflammatory effects of novel sinomenine derivatives.

    PubMed

    Zhao, Zijian; Xiao, Jing; Wang, Jiancheng; Dong, Wanrong; Peng, Zhihong; An, Delie

    2015-12-01

    Sinomenine is an isoquinoline-type alkaloid found in Sinomenium acutum (Thunb.) Rehd. et Wils and S. acutum (Thunb.) Rehd. et Wils var. cinereum Rehd. et Wils. When used as a medicine, this compound exhibits anti-inflammatory properties; however, sinomenine's use as a medication is limited by side effects, a short half-life, and low efficacy. Owing to these limits, attempts have been made to synthesize sinomenine derivatives with enhanced efficacy. In this study, the anti-inflammatory effects of novel sinomenine derivatives (S1a-S1f) were examined on the basis of lipopolysaccharide-induced inflammatory factor expression in Raw264.7 cells, dimethylbenzene-induced ear oedema, and Evan's blue leakage in mice, and carrageenan-induced paw oedema in rats. Compared with sinomenine, the derivatives significantly inhibited the expression of the inflammatory factors IL-1β and IL-6 at the transcriptional and translational levels. Topical application of 3.250mg/kg of the derivatives also alleviated ear oedema. Compared with the vehicle, the derivatives significantly inhibited carrageenan-induced rat paw oedema after 6h. Among the derivatives, S1a exhibited the most potent anti-inflammatory activity. S1a also significantly increased the sinomenine-induced inhibition of Evan's blue leakage. Thus, S1a may elicit the strongest anti-inflammatory effects of the tested compounds. Based on these results, further development of this compound may be warranted.

  13. Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

    PubMed Central

    Yena, Maryna S.; Kotlyar, Iryna P.; Ogloblya, Olexandr V.; Rybalchenko, Volodymyr K.

    2016-01-01

    In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes. PMID:28101521

  14. Discovery of anti-inflammatory role of prostaglandin D2

    PubMed Central

    MURATA, Takahisa; MAEHARA, Toko

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin are one of the most frequently used classes of drug worldwide and inhibit prostaglandin (PG) production by inhibiting cyclooxygenase activity. Although NSAIDs are broadly used against inflammatory diseases, they have side effects including alimentary canal disorders, kidney damage, infection and cardiovascular disorders. Thus, it is necessary to elucidate the pathophysiological role of each PG in various diseases to develop better therapies with fewer and milder side effects. PGD2 is a PG that was identified in 1973 by Hamberg and is produced by the activities of cyclooxygenase and either hematopoietic or lipocalin-type PGD synthase. PGD2 exerts its physiological effects by stimulating two distinct G protein-coupled receptors, namely D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). The physiological role of PGD2 remains controversial. Some studies have reported that PGD2 has bronchoconstrictory and pro-inflammatory effects inducing immune cell accumulation. In contrast, other groups have reported that PGD2 has anti-inflammatory effects by inhibiting the recruitment of dendritic cells and neutrophils. We have investigated the pathophysiological role of PGD2 using various disease models and reported on its anti-inflammatory actions. Here, we review the anti-inflammatory roles of PGD2 and the underlying mechanisms. PMID:27498997

  15. Autonomic regulation of anti-inflammatory activities from salivary glands.

    PubMed

    Mathison, Ronald D; Davison, Joseph S; St Laurent, Chris D; Befus, A Dean

    2012-01-01

    The cervical sympathetic nerves which innervate the medial basal hypothalamus-hypophyseal complex, primary and secondary lymph organs, and numerous glands, such as the pineal, thyroid, parathyroid and salivary glands form a relevant neuroimmunoendocrine structure that is involved in the regulation of systemic homeostasis. The superior cervical ganglia and the submandibular glands form a 'neuroendocrine axis' called the cervical sympathetic trunk submandibular gland (CST-SMG) axis. The identification of this axis usurps the traditional view of salivary glands as accessory digestive structures and reinforces the view that they are important sources of systemically active immunoregulatory and anti-inflammatory factors whose release is intimately controlled by the autonomic nervous system, and in particular the sympathetic branch. An end component of the CST-SMG axis is the synthesis, processing and release of submandibular rat-1 protein (SMR1), a prohormone, that generates several different peptides, one from near its N-terminus called sialorphin and another from its C-terminus called - submandibular gland peptide-T (SGP-T). SGP-T formed the template for tripeptide fragment (FEG) and its metabolically stable D-isomeric peptide feG, which are potent inhibitors of allergy and asthma (IgE-mediated allergic reactions) and several non-IgE-mediated inflammations. The translation from rat genetics and proteomics to humans has yielded structural and functional correlates that hopefully will lead to the development of new medications and therapeutic approaches for difficult to treat disorders. Although the CST-SMG axis has barely been explored in humans recognition of the importance of this axis could facilitate an understanding and improved management of periodontal disease, and other diseases with a more systemic and nervous system basis such as asthma, autoimmunity, graft-versus-host disease and even Parkinson's disease.

  16. First total synthesis of antrocamphin A and its analogs as anti-inflammatory and anti-platelet aggregation agents.

    PubMed

    Lee, Chia-Lin; Huang, Chi-Huan; Wang, Hui-Chun; Chuang, Da-Wei; Wu, Ming-Jung; Wang, Sheng-Yang; Hwang, Tsong-Long; Wu, Chin-Chung; Chen, Yeh-Long; Chang, Fang-Rong; Wu, Yang-Chang

    2011-01-07

    Naturally occurring antrocamphin A (1) is a potent anti-inflammatory compound from the edible fungus Antrodia camphorata (Taiwanofungus camphoratus), whose wild fruiting body is used as a valuable folk medicine in Taiwan. This study is the first total synthesis of antrocamphin A (1) and its analogs. Their inhibition ability on NO release, superoxide anion generation, elastase release and platelet aggregation are reported herein.

  17. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

    PubMed

    Mostafa, Dina Mahmoud; Ammar, Nagwa Mohammed; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; Hussein, Rehab Ali; Awad, Gamal; El-Awdan, Sally Abdul-Wanees

    2015-01-01

    Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

  18. Anti-inflammatory effects of electronic signal treatment.

    PubMed

    Odell, Robert H; Sorgnard, Richard E

    2008-01-01

    Inflammation often plays a key role in the perpetuation of pain. Chronic inflammatory conditions (e.g. osteoarthritis, immune system dysfunction, micro-circulatory disease, painful neuritis, and even heart disease) have increased as baby boomers age. Medicine's current anti-inflammatory choices are NSAIDs and steroids; the value in promoting cure and side effect risks of these medications are unclear and controversial, especially considering individual patient variations. Electricity has continuously been a powerful tool in medicine for thousands of years. All medical professionals are, to some degree, aware of electrotherapy; those who directly use electricity for treatment know of its anti-inflammatory effects. Electronic signal treatment (EST), as an extension of presently available technology, may reasonably have even more anti-inflammatory effects. EST is a digitally produced alternating current sinusoidal electronic signal with associated harmonics to produce theoretically reasonable and/or scientifically documented physiological effects when applied to the human body. These signals are produced by advanced electronics not possible even 10 to 15 years ago. The potential long-lasting anti-inflammatory effects of some electrical currents are based on basic physical and biochemical facts listed in the text below, namely that of stimulating and signaling effective and long-lasting anti-inflammatory effects in nerve and muscle cells. The safety of electrotherapeutic treatments in general and EST in particular has been established through extensive clinical use. The principles of physics have been largely de-emphasized in modern medicine in favor of chemistry. These electrical treatments, a familiar application of physics, thus represent powerful and appropriate elements of physicians' pain care armamentaria in the clinic and possibly for prescription for use at home to improve overall patient care and maintenance of quality of life via low-risk and potentially

  19. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  20. Cyclooxygenase-2 inhibition reduces stress-induced affective pathology

    PubMed Central

    Gamble-George, Joyonna Carrie; Baldi, Rita; Halladay, Lindsay; Kocharian, Adrina; Hartley, Nolan; Silva, Carolyn Grace; Roberts, Holly; Haymer, Andre; Marnett, Lawrence J; Holmes, Andrew; Patel, Sachin

    2016-01-01

    Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders. DOI: http://dx.doi.org/10.7554/eLife.14137.001 PMID:27162170

  1. Multifaceted roles of cyclooxygenase-2 in lung cancer.

    PubMed

    Riedl, Karen; Krysan, Kostyantyn; Põld, Mehis; Dalwadi, Harnisha; Heuze-Vourc'h, Nathalie; Dohadwala, Mariam; Liu, Ming; Cui, Xiaoyan; Figlin, Robert; Mao, Jenny T; Strieter, Robert; Sharma, Sherven; Dubinett, Steven M

    2004-06-01

    Lung cancer is the leading cause of cancer death in the United States. Although the low 5-year survival rate (under 15%) has changed minimally in the last 25 years, new agents and combinations of agents that target tumor proliferation, invasion, and survival may lead to improvement in patient outcomes. There is evidence that cyclooxygenase-2 (COX-2) is overexpressed in lung cancer and promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. COX-2 inhibitors have been found to inhibit tumor growth in animal models and have demonstrated responses when combined with conventional therapy in phase II clinical trials. Further understanding of the mechanisms involved in COX-2-mediated tumorigenesis and its interaction with other molecules in lung cancer may lead to improved therapeutic strategies for this disease. In addition, delineation of how COX-2-dependent genes modulate the malignant phenotype will provide novel insights in lung cancer pathogenesis.

  2. Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells

    PubMed Central

    Cha, Jae Hoon; Kim, Woo Kyoung; Ha, Ae Wha; Kim, Myung Hwan

    2017-01-01

    BACKGROUND/OBJECTIVES Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and 30 µM lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B (NF-κB), inhibitor kappa B (IκB), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) were determined via enzyme-linked immunosorbent assays. RESULTS In cells treated with lycopene and LPS, the mRNA expression of TNF-α, IL-1β, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of PGE2 and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of NF-κB and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS Lycopene restrains NF-κB and JNK activation, which causes inflammation, and suppresses the expression of TNF-α, IL-1β, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells. PMID:28386381

  3. Anti-inflammatory activity of β-patchoulene isolated from patchouli oil in mice.

    PubMed

    Zhang, Zhenbiao; Chen, Xiaoying; Chen, Hanbin; Wang, Lan; Liang, Jiali; Luo, Dandan; Liu, Yuhong; Yang, Hongmei; Li, Yucui; Xie, Jianhui; Su, Ziren

    2016-06-15

    β-Patchoulene (β-PAE) is a tricyclic sesquiterpene isolated from the oil of Pogostemon cablin (patchouli oil), which has been widely used in traditional Chinese medicine for the treatment of inflammatory diseases. However, as one of the major principle of patchouli oil, the biological activity of β-PAE has not been explored so far. In the present study, the anti-inflammatory activity in vivo, and the underlying mechanism, of β-PAE was investigated on experimental mice models of acute inflammation, i.e. xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results showed that β-PAE evoked a significant dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan and suppressed the increase of vascular permeability elicited by acetic acid. Histopathological analysis indicated that β-PAE could markedly decrease the cellular infiltration in paw tissue. β-PAE was also shown to significantly decrease the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in edema paw. In addition, carrageenan-induced production of some pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO), were suppressed in a dose-dependent manner in mice subjected to β-PAE pretreatment, and it also significantly down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further analysis revealed that β-PAE also inhibited the translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus and stabilize the conversion of nuclear factor-κBα (IκBα) level. These results provided additional chemical and pharmacological basis for the traditional application of P. cablin in inflammatory disorders.

  4. Anti-inflammatory and anti-catabolic effects of TENDOACTIVE® on human tenocytes in vitro.

    PubMed

    Shakibaei, M; Buhrmann, C; Mobasheri, A

    2011-09-01

    Tendons have a limited capacity for self-repair due to the low density and mitotic activity of tenocytes. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) have been identified as the main initiators of tendinopathies, stimulating inflammation, apoptosis and extracellular matrix (ECM) degradation. The aim of this study was to evaluate the potential of Tendoactive®, a newly developed proprietary nutraceutical formulation that includes mucopolysaccharides, collagen and vitamin C, in an in vitro model of tendon inflammation. The effects of Tendoactive® were studied in primary cultures of human tenocytes treated with IL-1β for up to 72 h. Expression of collagen type I, integrin β1, cyclo-oxygenase-2 (COX-2), caspase-3 and matrix metalloproteinase-1 (MMP-1) was monitored by western blotting. The effects of Tendoactive® on the expression, phosphorylation and nuclear translocation of protein components of the NF-κB system were studied by western blotting and immunofluorescence respectively. Treatment of tenocytes with Tendoactive® suppressed IL-1β-induced NF-κB activation and p65 nuclear translocation. These events correlated with down-regulation of NF-κB targets including COX-2, MMP-1 and activated caspase-3. Tendoactive® also reversed the IL-1β-induced down-regulation of collagen type I and β1-integrin receptor expression. These results indicate that Tendoactive® has nutraceutical potential as an anti-inflammatory agent for treating tendinopathy through suppression of NF-κB mediated IL-1β catabolic signalling pathways in tenocytes.

  5. The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2.

    PubMed

    Maioli, N A; Zarpelon, A C; Mizokami, S S; Calixto-Campos, C; Guazelli, C F S; Hohmann, M S N; Pinho-Ribeiro, F A; Carvalho, T T; Manchope, M F; Ferraz, C R; Casagrande, R; Verri, W A

    2015-04-01

    It is currently accepted that superoxide anion (O2•-) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO2), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO2 is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO2. The KO2-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO2 induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO2 also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO2-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO2 is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.

  6. Cardiovascular thrombotic events in arthritis trials of the cyclooxygenase-2 inhibitor celecoxib.

    PubMed

    White, William B; Faich, Gerald; Borer, Jeffrey S; Makuch, Robert W

    2003-08-15

    To determine whether the cyclooxygenase-2 (COX-2) inhibitor celecoxib affects cardiovascular thrombotic risk, we analyzed the incidence of cardiovascular events for celecoxib, placebo, and nonsteroidal anti-inflammatory drugs (NSAIDs) in the entire controlled, arthritis clinical trial database for celecoxib. The primary analysis used the Antiplatelet Trialists' Collaboration end points, which include: (1) cardiovascular, hemorrhagic, and unknown deaths, (2) nonfatal myocardial infarction, and (3) nonfatal stroke. Other secondary thrombotic events were also examined. Separate analyses were performed for all patients and for those not taking aspirin. Data from all controlled, completed arthritis trials of > or =4 weeks duration, including 13 new drug application studies and 2 large post-marketing trials (CLASS and SUCCESS) were included for analyses. Patients were randomized to celecoxib at doses from 100 to 400 mg twice daily (18,942 patients; 5,668.2 patient-years of exposure), diclofenac 50 to 75 mg twice daily, ibuprofen 800 mg thrice daily, naproxen 500 mg twice daily (combined NSAID exposure of 11,143 patients; 3,612.2 patient-years), or placebo (1,794 subjects; 199.9 subject-years). Data from a long-term uncontrolled trial with 5,209 patients (6,950 patients-years) treated with celecoxib were included in a supplemental analysis. The entire 15-trial database was searched for possible serious thrombotic events as well as to identify all deaths. For these patients, detailed clinical data were obtained and reviewed by 2 of the investigators (WBW and JSB), who were independently and blinded to exposure, to classify the event as primary, secondary, or neither. All analyses were done using the intent-to-treat population, and time-to-event analyses were performed using per-patient data. To examine heterogeneity of results among studies, tests of interaction were performed using the Cox model. Incidences of the primary and secondary events were not significantly

  7. Anti-inflammatory and cytotoxic activities of Bursera copallifera

    PubMed Central

    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

    2015-01-01

    Background: 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 Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:26664022

  8. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

    PubMed Central

    Bala, Suman; Sharma, Neha; Saini, Vipin

    2014-01-01

    Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. PMID:25383223

  9. 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

  10. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials.

    PubMed

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-09-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse.

  11. Investigation of the anti-inflammatory properties of hydroxypyridinones.

    PubMed Central

    Hewitt, S D; Hider, R C; Sarpong, P; Morris, C J; Blake, D R

    1989-01-01

    Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities. PMID:2730166

  12. Anti-inflammatory and antipyretic effects of boldine.

    PubMed

    Backhouse, N; Delporte, C; Givernau, M; Cassels, B K; Valenzuela, A; Speisky, H

    1994-10-01

    Boldine, an antioxidant alkaloid isolated from Peumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o. In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 microM. The latter in vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exerted in vivo.

  13. Anti-inflammatory activity of Heliotropium strigosum in animal models.

    PubMed

    Khan, Haroon; Khan, Murad Ali; Gul, Farah; Hussain, Sajjid; Ashraf, Nadeem

    2015-12-01

    The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models.

  14. Novel anti-inflammatory therapies for the treatment of atherosclerosis.

    PubMed

    Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L

    2015-06-01

    The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels.

  15. Anti-inflammatory lignanamides and monoindoles from Alocasia macrorrhiza.

    PubMed

    Huang, Wenjie; Li, Chuan; Wang, Yihai; Yi, Xiaomin; He, Xiangjiu

    2017-03-01

    Five new lignanamides (1-5), and one new monoindole alkaloid (6), along with eight known compounds (7-14) were isolated and identified from the rhizomes of Alocasia macrorrhiza (giant taro). All purified compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells, and the antiproliferative activities against human nasopharyngeal carcinoma epithelial (CNE-1), human gastric carcinoma (MGC-803), and human breast cancer (MCF-7) cell lines by MTT method. Compounds 2, 4, 7 and 8 exhibited significant inhibitory effects on NO production with the IC50 values of 2.35±0.38, 9.20±0.94, 3.45±0.39 and 7.96±0.56μM, respectively. The results suggested the lignanamides and monoindoles might be responsible for the anti-inflammatory activity of giant taro and might be potential anti-inflammatory candidates.

  16. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  17. Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

    PubMed Central

    Bosquesi, Priscila Longhin; Melo, Thais Regina Ferreira; Vizioli, Ednir Oliveira; dos Santos, Jean Leandro; Chung, Man Chin

    2011-01-01

    The design of new drugs with better physiochemical properties, adequate absorption, distribution, metabolism, and excretion, effective pharmacologic potency and lacking toxicity remains is a challenge. Inflammation is the initial trigger of several different diseases, such as Alzheimer's disease, asthma, atherosclerosis, colitis, rheumatoid arthritis, depression, cancer; and disorders such as obesity and sexual dysfunction. Although inflammation is not the direct cause of these disorders, inflammatory processes often increase related pain and suffering. New anti-inflammatory drugs developed using molecular hybridization techniques to obtain multiple-ligand drugs can act at one or multiple targets, allowing for synergic action and minimizing toxicity. This work is a review of new anti-inflammatory drugs developed using the molecular modification approach. PMID:27721332

  18. Anti-inflammatory effects of Lacto-Wolfberry in a mouse model of experimental colitis

    PubMed Central

    Philippe, David; Brahmbhatt, Viral; Foata, Francis; Saudan, Yen; Serrant, Patrick; Blum, Stephanie; Benyacoub, Jalil; Vidal, Karine

    2012-01-01

    .0244), IL-6 (-LWB vs +LWB, 318 ± 99 μg/L vs 117 ± 18 μg/L, P = 0.0315) and other pro-inflammatory proteins such as cyclooxygenase-2 (-LWB vs +LWB, 0.95 ± 0.12 AU vs 0.36 ± 0.11 AU, P = 0.0036) and phosphorylated signal transducer and activator of transcription-3 (-LWB vs +LWB, 0.51 ± 0.15 AU vs 0.1 ± 0.04 AU, P = 0.057). Moreover, antioxidant biomarkers, including expression of gene encoding for the glutathione peroxidase, in the colon and the plasma anti-oxidant capacity were significantly increased by supplementation with LWB (-LWB vs +LWB, 1.2 ± 0.21 mmol/L vs 2.1 ± 0.19 mmol/L, P = 0.0095). CONCLUSION: These results demonstrate the anti-inflammatory properties of LWB and suggest that the underlying mechanism is at least in part due to NF-κB inhibition and improved anti-oxidative capacity. PMID:23082051

  19. Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone.

    PubMed

    Olsen, N V; Jensen, N G; Hansen, J M; Christensen, N J; Fogh-Andersen, N; Kanstrup, I L

    1999-10-01

    Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin-aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF(1alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A(2) synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of

  20. Anti-inflammatory activity of arctigenin from Forsythiae Fructus.

    PubMed

    Kang, Hyo Sook; Lee, Ji Yun; Kim, Chang Jong

    2008-03-05

    Oleaceae Forsythiae Fructus has been used for anti-inflammatory, diuretics, antidote, and antibacterials in traditional herbal medicine. Our previous screening of medicinal plants showed that methanol (MeOH) extract of Forsythiae Fructus had significant anti-inflammatory activity, but the active ingredients remain unclear. For isolation of active ingredient of MeOH extract of Forsythiae Fructus, it was partitioned with n-hexane and ethylacetate (EtOAc), and arctigenin was isolated from EtOAc fraction by column chromatography with anti-inflammatory activity-guided separation. Its activity was evaluated in the animal models of inflammation including myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities in the edematous tissues homogenate, and silica-induced reactive oxygen species (ROS) production in the RAW 264.7 cell line. It was shown that arctigenin (100 mg/kg) had significantly decreased not only carrageenan-induced paw edema 3 and 4h after injection of carrageenan, arachidonic acid (AA)-induced ear edema at a painting dose of 0.1-1.0mg/ear, and acetic acid-induced writhing response and acetic acid-induced capillary permeability accentuation at an oral dose of 25-100, and 100 mg/kg, respectively, but also MPO and EPO activities at a painting dose of 0.1-1.0mg/ear in the AA-induced edematous tissues homogenate as indicators of neutrophils and eosinophils recruitment into the inflamed tissue. Further, arctigenin (0.1-10 microM) also significantly inhibited the intracellular ROS production by silica. These results indicate that arctigenin is a bioactive agent of Forsythiae Fructus having significant anti-inflammatory action by inhibition of the exudation, and leukocytes recruitment into the inflamed tissues. The pharmacologic mechanism of action of arctigenin may be due to the inhibition of release/production of inflammatory mediators such as AA metabolites and free radicals.

  1. Immunosuppressive and anti-inflammatory activities of sinomenine.

    PubMed

    Wang, Quanxing; Li, Xiao-Kang

    2011-03-01

    Sinomenine (SN), a pure compound extracted from the Sinomenium acutum plant, has been found to inhibit T- and B-lymphocyte activation, proliferation and function and to interfere with the differentiation, recruitment and function of several other cell types, such as dendritic cells (DC). SN has demonstrated its potential anti-inflammatory role for treating immune-related disorders in experimental animal models and in some clinical applications. This review will summarize its potential effects, mechanisms and applications.

  2. Synthesis and anti-inflammatory activities of novel dihydropyranoaurone derivatives.

    PubMed

    Wang, Zheng; Bae, Eun Ju; Han, Young Taek

    2017-04-10

    A novel series of dihydropyranoaurone derivatives were synthesized and evaluated as potential anti-inflammatory agents. Late-stage derivatization by versatile piperazine-catalyzed aldol reaction between dihydropyanobenzofuran intermediate 2 and diverse aldehydes readily afforded the novel dihydropyranoaurone analogs. Evaluation of the synthesized dihydropyranoaurone derivatives and related compounds regarding their inhibiting inducible nitric oxide synthase and nitrite production of lipopolysaccaride-stimulated RAW 264.7 cells provided insight into the structure-activity relationship of aurone derivatives.

  3. An anti-inflammatory and immunomodulatory polysaccharide from Orbignya phalerata.

    PubMed

    da Silva, B P; Parente, J P

    2001-12-01

    A polysaccharide, a glucan with mean M(r) of 1.0 x 10(6) (MP1), was isolated from the mesocarp of fruits of Orbignya phalerata. Chemical and spectroscopic studies indicated that MP1 has a highly branched glucan type structure composed of alpha-(1-->4) linked D-glucopyranose residues with (3-->4), (4-->6), and with (3-->6) branching points. MP1 enhanced phagocytosis in vivo and exhibited anti-inflammatory activity.

  4. Anti-inflammatory activity and composition of Senecio salignus Kunth.

    PubMed

    González, Cuauhtemoc Pérez; Vega, Roberto Serrano; González-Chávez, Marco; Sánchez, Miguel Angel Zavala; Gutiérrez, Salud Pérez

    2013-01-01

    We investigated the anti-inflammatory activity of Senecio salignus. This medicinal plant is often used in Mexico for the treatment of fever and rheumatism. Chloroform and methanol extracts of the plant were tested on 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced edema in mice ears. The methanol extract of the plant inhibited edema by 36 ± 4.4% compared with the control, while the chloroform extract exhibited an even greater level of inhibition (64.1%). The chloroform extract was then fractionated, and the composition of the active fraction was determined by GC-MS. The anti-inflammatory activity of this fraction was then tested on TPA-induced ear edema in mice, and we found that the active fraction could inhibit edema by 46.9%. The anti-inflammatory effect of the fraction was also tested on carrageenan-induced paw edema in rats at doses of 100 mg/kg; a 58.9 ± 2.8% reduction of the edema was observed 4 h after administration of carrageenan, and the effect was maintained for 5 h.

  5. Anti-Inflammatory Activity and Composition of Senecio salignus Kunth

    PubMed Central

    Pérez González, Cuauhtemoc; Serrano Vega, Roberto; González-Chávez, Marco; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

    2013-01-01

    We investigated the anti-inflammatory activity of Senecio salignus. This medicinal plant is often used in Mexico for the treatment of fever and rheumatism. Chloroform and methanol extracts of the plant were tested on 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced edema in mice ears. The methanol extract of the plant inhibited edema by 36 ± 4.4% compared with the control, while the chloroform extract exhibited an even greater level of inhibition (64.1%). The chloroform extract was then fractionated, and the composition of the active fraction was determined by GC-MS. The anti-inflammatory activity of this fraction was then tested on TPA-induced ear edema in mice, and we found that the active fraction could inhibit edema by 46.9%. The anti-inflammatory effect of the fraction was also tested on carrageenan-induced paw edema in rats at doses of 100 mg/kg; a 58.9 ± 2.8% reduction of the edema was observed 4 h after administration of carrageenan, and the effect was maintained for 5 h. PMID:23691512

  6. Structural characterization of anti-inflammatory immunoglobulin G Fc proteins.

    PubMed

    Ahmed, Alysia A; Giddens, John; Pincetic, Andrew; Lomino, Joseph V; Ravetch, Jeffrey V; Wang, Lai-Xi; Bjorkman, Pamela J

    2014-09-09

    Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation, and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of intravenous IgG requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of intravenous IgG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal α2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully disialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro-inflammatory to anti-inflammatory activity of the Fc.

  7. Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice.

    PubMed

    Riça, Ingred G; Netto, Chaquip D; Rennó, Magdalena N; Abreu, Paula A; Costa, Paulo R R; da Silva, Alcides J M; Cavalcante, Moisés C M

    2016-09-15

    Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties and also shows great inhibitory effect on TNF-α release in vitro. Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)-induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked neutrophil infiltration to the lungs which was reduced by intraperitoneal treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118 administration resulted in decrease of NF-κB activation and KC level in lungs, with a pronounced inhibitory effect on TNF-α release, measured in bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling analysis, including docking to estrogen receptors α and β. Results suggested that (+/-)-LQB-118 may bind to both receptors, with a similar orientation to 17-β-estradiol. Together, these results showed that (+/-)-LQB-118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-α release and NF-κB activation, which may be related to the estrogen receptor binding.

  8. UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

    PubMed Central

    Couteau, Céline; Chauvet, Catherine; Paparis, Eva; Coiffard, Laurence

    2012-01-01

    Background To explain observed differences during SPF determination using either an in vivo or in vitro method, we hypothesized on the presence of ingredients having anti-inflammatory properties. Methodology/Principal Findings To research our hypothesis, we studied the 21 UV filters both available on the market and authorized by European regulations and subjected these filters to the phorbol-myristate-acetate test using mice. We then catalogued the 13 filters demonstrating a significant anti-inflammatory effect with edema inhibition percentages of more than 70%. The filters are: diethylhexyl butamido triazone (92%), benzophenone-5 and titanium dioxide (90%), benzophenone-3 (83%), octocrylène and isoamyl p-methoxycinnamate (82%), PEG-25 PABA and homosalate (80%), octyl triazone and phenylbenzimidazole sulfonic acid (78%), octyl dimethyl PABA (75%), bis-ethylhexyloxyphenol methoxyphenyl triazine and diethylamino hydroxybenzoyl hexylbenzoate (70%). These filters were tested at various concentrations, including their maximum authorized dose. We detected a dose-response relationship. Conclusions/Significance The anti-inflammatory effect of a sunscreen ingredient may affect the in vivo SPF value. PMID:23284607

  9. Anti-inflammatory effect of Houttuynia cordata injection.

    PubMed

    Lu, H M; Liang, Y Z; Yi, L Z; Wu, X J

    2006-03-08

    Houttuynia cordata (Saururaceae) injection (HCI) is a traditional Chinese medicine used in China. It was chosen as one of eight types of traditional Chinese medicine that play a unique role in severe acute respiratory syndrome (SARS) owing to the effect of curbing inflammation. In order to validate this plausible anti-inflammatory property, the chemical composition of HCI has been analysed by GC/MS, 22 components were identified, and the inflammation induced by carrageenan in the rat pleurisy model and by xylene in the mice ear edema model was adopted to study the anti-inflammatory activity of HCI. Injection of carrageenan into the pleural cavity elicited an acute inflammatory response characterized by protein rich fluid accumulation and leukocyte infiltration in the pleural cavity. The peak inflammatory response was obtained at 24 h when the fluid volume, protein concentration, C-reactive protein and cell infiltration were maximums. The results showed that these parameters were attenuated by HCI at any dose and touched bottom at dose of 0.54 ml/100 g, although less strong than dexamethasone. This drug was also effective in inhibiting xylene induced ear edema, and the percentage of inhibition came to 50% at dose of 80 microl/20 g. The results clearly indicate that HCI have anti-inflammatory activity.

  10. ANTI-INFLAMMATORY ACTIVITY OF MIRABILIS JALAPA LINN. LEAVES

    PubMed Central

    Nath, Lekshmi. R.; Manjunath, K. P.; Savadi, R. V.; Akki, K. S.

    2010-01-01

    Mirabilis Jalapa Linn. is a widely used traditional medicine in many parts of the world for the treatment of various diseases viz. virus inhibitory activity, anti tumour activity. It is claimed in traditional medicine that the leaves of the plant are used in the treatment of inflammation. In the present study, the total alcoholic extract and successive petroleum ether fractions of leaves of Mirabilis Jalapa Linn were screened for its anti-inflammatory activity using carageenan induced rat paw edema and cotton pellet induced granuloma models. The total alcoholic extract at the dose of 300 mg/kg p.o and successive petroleum ether fraction at the dose of 200 mg/kg exhibited significant anti-inflammatory activity in carrageenan induced paw edema model (p<0.01). In cotton pellet granuloma model, the total alcoholic extract at the dose of 300 mg/kg and successive petroleum ether fraction at the dose of 200 mg/kg inhibited granuloma formation significantly (p<0.05) indicating that both test samples inhibit the increase in number of fibroblasts and synthesis of collagen and mucopolysaccharides during granuloma tissue formation during the chronic inflammation. These experimental results have established a pharmacological evidence for the folklore claim of the drug to be used as an anti inflammatory agent. PMID:24825972

  11. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-05

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.

  12. Anti-inflammatory prostaglandins for the prevention of preterm labour.

    PubMed

    Sykes, Lynne; MacIntyre, David A; Teoh, Tiong Ghee; Bennett, Phillip R

    2014-08-01

    Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ(12,14)PGJ2 (15d-PGJ2) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15d-PGJ2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.

  13. Evaluation of Anticancer, Antioxidant, and Possible Anti-inflammatory Properties of Selected Medicinal Plants Used in Indian Traditional Medication

    PubMed Central

    Shaikh, Rafik; Pund, Mahesh; Dawane, Ashwini; Iliyas, Sayyed

    2014-01-01

    The present study was carried out to evaluate the anticancer, antioxidant, and possible anti-inflammatory properties of diverse medicinal plants frequently used in Indian traditional medication. The selected botanicals such as Soymida fembrifuga (Roxb.) A. Juss. (Miliaceae), Tinospora cordifolia (Willd.) Miers. (Menispermaceae), Lavandula bipinnata (L.) O. Ktze. (Lamiaceae), and Helicteres isora L. (Sterculiaceae) extracted in different solvents were evaluated for their in vitro anticancer and antioxidant activities. The results obtained indicate that H. isora has potent cytotoxic activity toward the selected cancer cells such as HeLa-B75 (34.21 ± 0.24%), HL-60 (30.25 ± 1.36%), HEP-3B (25.36 ± 1.78%), and PN-15 (29.21 ± 0.52%). Interestingly, the selected botanicals selectively inhibited cyclooxygenase-2 (COX-2) more than (COX-1), which are the key enzymes implicated in inflammation. COX-2 inhibition was observed to be in the range of 19.66-49.52% as compared to COX-1 inhibition (3.93-19.61%). The results of the antioxidant study revealed that the selected plants were found to be effective 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging agents. High-performance thin layer chromatography (HPTLC) fingerprint of flavonoids was used as a measure of quality control of the selected plant samples. The results of the present findings strengthen the potential of the selected plants as a resource for the discovery of novel anticancer, anti-inflammatory, and antioxidant agents. PMID:25379467

  14. Evaluation of Anticancer, Antioxidant, and Possible Anti-inflammatory Properties of Selected Medicinal Plants Used in Indian Traditional Medication.

    PubMed

    Shaikh, Rafik; Pund, Mahesh; Dawane, Ashwini; Iliyas, Sayyed

    2014-10-01

    The present study was carried out to evaluate the anticancer, antioxidant, and possible anti-inflammatory properties of diverse medicinal plants frequently used in Indian traditional medication. The selected botanicals such as Soymida fembrifuga (Roxb.) A. Juss. (Miliaceae), Tinospora cordifolia (Willd.) Miers. (Menispermaceae), Lavandula bipinnata (L.) O. Ktze. (Lamiaceae), and Helicteres isora L. (Sterculiaceae) extracted in different solvents were evaluated for their in vitro anticancer and antioxidant activities. The results obtained indicate that H. isora has potent cytotoxic activity toward the selected cancer cells such as HeLa-B75 (34.21 ± 0.24%), HL-60 (30.25 ± 1.36%), HEP-3B (25.36 ± 1.78%), and PN-15 (29.21 ± 0.52%). Interestingly, the selected botanicals selectively inhibited cyclooxygenase-2 (COX-2) more than (COX-1), which are the key enzymes implicated in inflammation. COX-2 inhibition was observed to be in the range of 19.66-49.52% as compared to COX-1 inhibition (3.93-19.61%). The results of the antioxidant study revealed that the selected plants were found to be effective 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging agents. High-performance thin layer chromatography (HPTLC) fingerprint of flavonoids was used as a measure of quality control of the selected plant samples. The results of the present findings strengthen the potential of the selected plants as a resource for the discovery of novel anticancer, anti-inflammatory, and antioxidant agents.

  15. MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis.

    PubMed

    Cuevas, Víctor D; Anta, Laura; Samaniego, Rafael; Orta-Zavalza, Emmanuel; Vladimir de la Rosa, Juan; Baujat, Geneviève; Domínguez-Soto, Ángeles; Sánchez-Mateos, Paloma; Escribese, María M; Castrillo, Antonio; Cormier-Daire, Valérie; Vega, Miguel A; Corbí, Ángel L

    2017-03-01

    Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, whereas the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knockdown of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the coexpression of MAFB and MAFB-target genes in CD163(+) tissue-resident and tumor-associated macrophages. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from multicentric carpotarsal osteolysis (Online Mendelian Inheritance in Man #166300), a pathology caused by mutations in the MAFB gene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages.

  16. Anti-inflammatory activity of Pistacia khinjuk in different experimental models: isolation and characterization of its flavonoids and galloylated sugars.

    PubMed

    Esmat, Ahmed; Al-Abbasi, Fahad A; Algandaby, Mardi M; Moussa, Ashaimaa Y; Labib, Rola M; Ayoub, Nahla A; Abdel-Naim, Ashraf B

    2012-03-01

    The present study aimed at isolating and elucidating the structure of the main components of Pistacia khinjuk L. and exploring its potential anti-inflammatory effect in different experimental models. The extract was evaluated for anti-inflammatory activity by measuring paw volume in three experimental models. Then, prostaglandin E₂ (PGE₂) level, ear edema, tissue myeloperoxidase (MPO) activity, histopathology, nitric oxide (NO) level, and tumor necrosis factor-α (TNF-α) level were assessed. Seven phenolic compounds, mainly flavonoids and galloylated compounds, were isolated from the aqueous methanol extract: gallic acid (1), methyl gallate (2), quercetin-3-O-β-D-⁴C₁-galactopyranoside (hyperin) (3), myricetin-3-O-α-L-¹C₄-rhamnopyranoside (myricitrin) (4), 1,6-digalloyl-β-D-glucose (5), 1,4-digalloyl-β-D-glucopyranoside (6), and 2,3-di-O-galloyl-(α/β)-⁴C₁-glucopyranose (nilocitin) (7). The anti-inflammatory activity was evidenced by decreased carrageenan-induced rat paw edema and PGE₂ elevation. In the croton oil-induced ear edema model, MPO activity was significantly inhibited, and inflammatory histopathological changes were ameliorated. In the rat air pouch model, NO generation and TNF-α release were significantly inhibited. The isolation and nuclear magnetic resonance spectral data of compound 6 from the genus Pistacia are revealed for the first time. Also, P. khinjuk L. aqueous methanol extract possesses anti-inflammatory activity in several experimental models.

  17. Radical scavenging glycoprotein inhibiting cyclooxygenase-2 and thromboxane A2 synthase from aloe vera gel.

    PubMed

    Yagi, A; Kabash, A; Mizuno, K; Moustafa, S M; Khalifa, T I; Tsuji, H

    2003-03-01

    An active glycoprotein fraction containing 58 % protein was isolated from Aloe vera gel by precipitation with 55 % ammonium sulfate followed by gel permeation using DEAE-Sephacel A-25, Sepharose 6B and Sephadex G-50 columns in a yield of 3 x 10 -3 %. The glycoprotein fraction showed a single band corresponding to a subunit of verectin at the same position when stained with both Coomassie brilliant blue and periodic acid-Schiff reagents on 18 % SDS-PAGE. The molecular weight (14 kDa) was confirmed by Sephadex G-50 column chromatography. The glycoprotein fraction showed a radical scavenging activity against superoxide anion generated by the xanthine-xanthine oxidase system as well as inhibition of cyclooxygenase-2 and reduction of thromboxane A 2 synthase level in vitro.

  18. Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: identification of a lead for anti-inflammatory drug.

    PubMed

    Shaveta; Singh, Amrinder; Kaur, Matinder; Sharma, Surbhi; Bhatti, Rajbir; Singh, Palwinder

    2014-04-22

    Conjugates of chromone-indole and chromone-pyrazole were screened for cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitory activities. Compounds 8 and 9 were identified as preferred inhibitors of COX-2 over the other two enzymes. Their IC50 for COX-2 was 29 nM and 20 nM, respectively and selectivity indices (SI) for COX-2 over COX-1 was 46 and 337. NMR, mass spectral studies and molecular modelling also indicated preferential interactions of compounds 8 and 9 with COX-2. Tested on albino mice against capsaicin induced algesia, compound 8 exhibited analgesic potential comparable to diclofenac. In addition to the biological profile, the desirable physico-chemical properties of these compounds make them promising leads for anti-inflammatory drugs.

  19. An efficient total synthesis of a potent anti-inflammatory agent, benzocamphorin F, and its anti-inflammatory activity.

    PubMed

    Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung

    2012-01-01

    A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo.

  20. An Efficient Total Synthesis of a Potent Anti-Inflammatory Agent, Benzocamphorin F, and Its Anti-Inflammatory Activity

    PubMed Central

    Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung

    2012-01-01

    A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo. PMID:22949872

  1. Role of cyclooxygenase-2 in intestinal injury in neonatal rats.

    PubMed

    Lu, Hui; Zhu, Bing

    2014-11-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature neonates. The pathogenesis of NEC remains poorly understood. The present study aimed to investigate the dynamic change and role of cyclooxygenase-2 (COX-2) in neonatal rats with intestinal injury. Wistar rats, <24 h in age, received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileal tissues were collected at 1, 3, 6, 12 and 24 h following the LPS challenge for histological evaluation of NEC and for measurements of COX-2 mRNA. The correlation between the degree of intestinal injury and expression of COX-2 mRNA was determined. The LPS-injected pups showed a significant increase in injury scores compared to the control, and the most deteriorating change was at 12 h. COX-2 mRNA expression was upregulated following LPS injection. There was a significantly positive correlation between COX-2 mRNA and the grade of intestinal injury within 12 h, whereas COX-2 mRNA expression had a significantly negative correlation with the severity of intestinal injury at 24 h. COX-2 plays an important role in LPS-induced intestinal injury and the repair processes. Caution should be exerted concerning the potential therapeutic uses of COX-2 inhibitors or promoters in NEC.

  2. Crystal structure of rofecoxib bound to human cyclooxygenase-2.

    PubMed

    Orlando, Benjamin J; Malkowski, Michael G

    2016-10-01

    Rofecoxib (Vioxx) was one of the first selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) to be approved for use in humans. Within five years after its release to the public, Vioxx was withdrawn from the market owing to the adverse cardiovascular effects of the drug. Despite the widespread knowledge of the development and withdrawal of Vioxx, relatively little is known at the molecular level about how the inhibitor binds to COX-2. Vioxx is unique in that the inhibitor contains a methyl sulfone moiety in place of the sulfonamide moiety found in other coxibs such as celecoxib and valdecoxib. Here, new crystallization conditions were identified that allowed the structural determination of human COX-2 in complex with Vioxx and the structure was subsequently determined to 2.7 Å resolution. The crystal structure provides the first atomic level details of the binding of Vioxx to COX-2. As anticipated, Vioxx binds with its methyl sulfone moiety located in the side pocket of the cyclooxygenase channel, providing support for the isoform selectivity of this drug.

  3. Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

    PubMed

    Torricelli, Federica; Mandato, Vincenzo Dario; Farnetti, Enrico; Abrate, Martino; Casali, Bruno; Ciarlini, Gino; Pirillo, Debora; Gelli, Maria Carolina; Costagliola, Luigi; Nicoli, Davide; Palomba, Stefano; La Sala, Giovanni Battista

    2015-09-01

    The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

  4. Cyclooxygenase-2 expression in primary and metastatic Merkel cell carcinoma.

    PubMed

    Joachims, Zohar; Feinmesser, Raphael; Purim, Ofer; Halpern, Marisa; Brenner, Baruch; Fenig, Eyal; Roizman, Pepi; Sulkes, Jaqueline; Feinmesser, Meora

    2008-10-01

    Cyclooxygenase-2 (COX-2) is involved in the development and progression of many tumors, and its inhibition has been shown to block tumor growth. This study examined COX-2 expression in primary and metastatic Merkel cell carcinoma (MCC). Formalin-fixed paraffin-embedded tissues from 26 primary MCCs and 7 lymph node metastases were stained immunohistochemically with a monoclonal antibody directed against COX-2, and the percentage and intensity of staining were analyzed semiquantitatively. Immunopositivity for COX-2 was found in 20 primary tumors (77%), and was diffuse in 16 of them (80%). Staining intensity was strong in 5 tumors (19%), moderate in 6 (23%), and weak in 9 (35%). Five metastases (71%) showed similar staining. Prominent mitotic activity was associated with more diffuse COX-2 immunopositivity. No association was found between COX-2 expression and outcome. This study confirms that most MCCs express COX-2 and shows that COX-2 expression is related to one parameter of aggressive behavior--a high mitotic rate--but not to any others. The possibility of treating MCC with COX-2 inhibitors should be considered.

  5. Crystal structure of rofecoxib bound to human cyclooxygenase-2

    SciTech Connect

    Orlando, Benjamin J.; Malkowski, Michael G.

    2016-10-26

    Rofecoxib (Vioxx) was one of the first selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) to be approved for use in humans. Within five years after its release to the public, Vioxx was withdrawn from the market owing to the adverse cardiovascular effects of the drug. Despite the widespread knowledge of the development and withdrawal of Vioxx, relatively little is known at the molecular level about how the inhibitor binds to COX-2. Vioxx is unique in that the inhibitor contains a methyl sulfone moiety in place of the sulfonamide moiety found in other coxibs such as celecoxib and valdecoxib. Here, new crystallization conditions were identified that allowed the structural determination of human COX-2 in complex with Vioxx and the structure was subsequently determined to 2.7- Å resolution. The crystal structure provides the first atomic level details of the binding of Vioxx to COX-2. As anticipated, Vioxx binds with its methyl sulfone moiety located in the side pocket of the cyclooxygenase channel, providing support for the isoform selectivity of this drug.

  6. Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions.

    PubMed

    Takei, Miwa; Kobayashi, Makiko; Herndon, David N; Pollard, Richard B; Suzuki, Fujio

    2006-09-01

    In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN.

  7. Expression of cyclooxygenase-2 (COX-2) in pituitary tumours

    PubMed Central

    Sokołowski, Grzegorz; Bałdys-Waligórska, Agata; Trofimiuk, Małgorzata; Adamek, Dariusz; Hubalewska-Dydejczyk, Alicja; Gołkowski, Filip

    2012-01-01

    Summary Background Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours. Material/Methods We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. Results COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size. Conclusions COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours. PMID:22460097

  8. Anti-inflammatory effects of essential oils from Mangifera indica.

    PubMed

    Oliveira, R M; Dutra, T S; Simionatto, E; Ré, N; Kassuya, C A L; Cardoso, C A L

    2017-03-16

    Mangifera indica is widely found in Brazil, and its leaves are used as an anti-inflammatory agent in folk medicine. The aim of this study is to perform composition analysis of essential oils from the M. indica varieties, espada (EOMIL1) and coração de boi (EOMIL2), and confirm their anti-inflammatory properties. Twenty-three volatile compounds were identified via gas chromatography-mass spectrometry (GC-MS) in two essential oils from the leaves. Paw edema and myeloperoxidase (MPO) activity were evaluated using the carrageenan-induced paw model, while leukocyte migration was analyzed using the pleurisy model. At oral doses of 100 and 300 mg/kg, the essential oils significantly reduced edema formation and the increase in MPO activity induced by carrageenan in rat paws. For a dose of 300 mg/kg EOMIL1, 62 ± 8% inhibition of edema was observed, while EOMIL2 led to 51 ± 7% inhibition of edema. At a dose of 100 mg/kg, the inhibition was 54 ± 9% for EOMIL1 and 37 ± 7% for EOMIL2. EOMIL1 and EOMIL2 significantly reduced MPO activity at doses of 100 mg/kg (47 ± 5 and 23 ± 8%, respectively) and 300 mg/kg (50 ± 9 and 31 ± 7%, respectively). In the pleurisy model, inhibitions were also observed for EOMIL1 and EOMIL2 in the leukocyte migration test. The results of the present study show that essential oils from M. indica differ in chemical composition and anti-inflammatory activity in rats.

  9. Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats

    PubMed Central

    Abo-dola, Marium A.; Lutfi, Mohamed F.

    2016-01-01

    Background There were no studies on the anti-inflammatory activity of Euphorbia aegyptiaca, though it is commonly used by Sudanese herbalists in the treatment of rheumatoid arthritis. Objectives To determine phytochemical constituents of Euphorbia aegyptiaca To investigate the anti-inflammatory activity of Euphorbia aegyptiaca in rats. Methodology Plant material was extracted by ethanol and phytochemical screening was done according to standard methods. The thickness of Albino rats’ paws were measured before injection of 0.1 ml of 1% formalin in the sub planter region and then, 1, 2, 3, 4 and 24 hours after oral dose of ethanolic extract of Euphorbia aegyptiaca at a rate of 400mg/kg, 800mg/kg, indomethacin (5mg/kg) and normal saline (5ml/kg). Edema inhibition percentage (EI%) and mean paw thickness (MPT) were measured in the different groups and compared using appropriate statistical methods. Results The phytochemical screening revealed the presence of saponins, cumarins, flavonoids, tannins, sterols, triterpenes, and absence of alkaloids, anthraquinones glycosides and cyanogenic glycosides. The mean of EI% of rats treated with indomethacin at a dose of 5 mg/kg over different time intervals (64.0%) was significantly lower compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (75.0%, P< 0.001), but higher compared to rats treated at higher dose of 400 mg/kg (57.4%, P< 0.001). In contrast, MPT of rats treated with indomethacin at a dose of 5 mg/kg (6.5±1.1 mm) was significantly higher compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (6.1±.7 mm, P< 0.001) as well as 400 mg/kg (5.9±.5, P< 0.001). Conclusion Euphorbia aegyptiaca ethanolic extract has a sustained dose-dependent anti-inflammatory activity. PMID:27004059

  10. Anti-inflammatory agents and inducibility of hepatic drug metabolism.

    PubMed

    Pappas, P; Stephanou, P; Vasiliou, V; Marselos, M

    1998-01-01

    Two rat liver cytosolic aldehyde dehydrogenases, ALDH1 and ALDH3c, are of particular interest because they are inducible by different classes of xenobiotics. ALDHI is mainly increased by phenobarbital-type inducers; polycyclic aromatic hydrocarbons (PAHs), such as 3- methylcholanthrene (3MC), increase ALDH3c enzyme activity in all rat species currently tested. In addition, ALDH3c has been found to reflect the subfamily CYPIA of cytochrome P-450, as well as other enzymes functionally related to the aryl hydrocarbon receptor (the "Ah-receptor enzyme battery"), which is activated by the same type of inducers. In the present study we investigated whether the induction of ALDH3c might be connected with a chemically produced aseptic inflammation of the hepatocyte. To answer this question, we examined the relationship between the induction of ALDH3c by 3MC and the arachidonic acid cascade. Different non-steroid anti-inflammatory drugs (NSAIDs) were tested in combination with 3MC and in post-treatment. The 3MC-induced ALDH3c activity was significantly diminished by the co-administered anti-inflammatory agents. Two microsomal enzyme activities (ethoxyresorufin-O-deethylase, EROD; aryl-hydrocarbon-hydroxylase, AHH) were also decreased. Similar results were obtained with NSAIDs administered to animals pre- treated with 3MC, as far as the ALDH3c activity was concerned, but not for the microsomal enzyme activity (EROD and AHH). In conclusion, the induction of ALDH3c, after PAH treatment, may be related to an aseptic inflammation of the hepatocytes. This effect is reduced by commonly used steroid and non-steroid anti- inflammatory drugs, and although the mechanism of inhibition has not yet been elucidated, it appears likely that ALDH3c and CYP1A activities are associated with the "acute phase" response.

  11. Heterotheca inuloides: anti-inflammatory and analgesic effect.

    PubMed

    Gené, R M; Segura, L; Adzet, T; Marin, E; Iglesias, J

    1998-03-01

    Heterotheca inuloides Cass. (Asteraceae) is used in the traditional medicine of Mexico. The aqueous extract obtained from the flowers of H. inuloides was assessed for anti-inflammatory activity by carrageenan-induced edema test. At 100 mg/kg, i.p, it produced 29% inhibition of inflammation. Ethyl ether (HI-1), butanol (HI-2) and aqueous fraction (HI-3) were obtained from the aqueous extract. The biological assay, by carrageenan-induced edema test, gave the following values (% inhibition): HI-1, 19.9; HI-2, 58.0 and HI-3, 30.0. HI-2 was significantly more effective than HI-1 and HI-3. The dose-effect curve of HI-2 was obtained and the calculated ED50 was 29.7 (22.5-39.2) mg/kg. The peritoneal examination after the treatment with HI-2 showed that the anti-inflammatory action of H. inuloides was not due to an irritating effect at the injection site. At 50-100 mg/kg, i.p., HI-2 inhibited inflammation induced by dextran (38.9-68.1% inhibition) and arachidonic acid (0-33.9%). No effect was observed at the same doses for zymosan or C16-paf-induced edema. In addition, HI-2 reduced abdominal constrictions in mice following injection of acetic acid: at 50-100 mg/kg, it gave 73.8-78.2% inhibition. The ulcerogenic assay showed that ulcer indices after HI-2 i.p. treatment were 0.5 +/- 0.5 at 50 mg/kg and 1.2 +/- 0.4 at 100 mg/kg. The results showed related anti-inflammatory activity and the analgesic effect of HI-2.

  12. Ginsenoside Rg3 Alleviates Lipopolysaccharide-Induced Learning and Memory Impairments by Anti-Inflammatory Activity in Rats

    PubMed Central

    Lee, Bombi; Sur, Bongjun; Park, Jinhee; Kim, Sung-Hun; Kwon, Sunoh; Yeom, Mijung; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

    2013-01-01

    The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer’s disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain. PMID:24244826

  13. Anti-Inflammatory Activity of Tanzawaic Acid Derivatives from a Marine-Derived Fungus Penicillium steckii 108YD142

    PubMed Central

    Shin, Hee Jae; Pil, Gam Bang; Heo, Soo-Jin; Lee, Hyi-Seung; Lee, Jong Seok; Lee, Yeon-Ju; Lee, Jihoon; Won, Ho Shik

    2016-01-01

    Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4), and K (5). The structures of tanzawaic acid derivatives 1–5 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis. These compounds significantly inhibited nitric oxide (NO) production and the new tanzawaic acid Q (1) inhibited the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA expressions in RAW 264.7 macrophages. Additionally, compound 1 reduced the mRNA levels of inflammatory cytokines. Taken together, the results of this study demonstrated that the new tanzawaic acid derivative inhibits LPS-induced inflammation. This is the first report on the anti-inflammatory activity of tanzawaic acid Q (1). PMID:26761016

  14. Comparative Impact on Prostanoid Biosynthesis of Celecoxib and the Novel Nonsteroidal Anti-Inflammatory Drug CG100649

    PubMed Central

    Skarke, C; Alamuddin, N; Lawson, JA; Cen, L; Propert, KJ; FitzGerald, GA

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate cardiovascular risk by disrupting cyclooxygenase-2 (COX-2)-dependent biosynthesis of prostacyclin (PGI2). CG100649 is a novel NSAID proposed to inhibit both COX-2 and carbonic anhydrase (CA)-I/-II. We compared its impact on prostanoid biosynthesis with that of celecoxib, an NSAID purposefully designed to selectively inhibit COX-2. In a controlled, double-blind randomized trial, single oral doses of 2 or 8 mg CG100649, 200 mg celecoxib, or placebo were well tolerated by healthy volunteers (n = 23). Both CG100649 and celecoxib had the effect of depressing urinary excretion of 2,3-dinor-6-keto-PGF1α (PGI-M); the effect of CG100649 was dose-dependent and more sustained (up to 240 h after the dose) than that of celecoxib. Neither CG100649 nor celecoxib significantly inhibited COX-1-dependent prostanoid formation. CA inhibition was not detected after administration of CG100649, despite its partitioning asymmetrically into erythrocytes. CG100649 and celecoxib are both relatively selective inhibitors of COX-2, but they differ in duration of action. Whether they have similar impact on cardiovascular events remains to be determined. PMID:22278334

  15. In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells.

    PubMed

    Wang, Yuan-Chuen; Huang, Kai-Ming

    2013-03-01

    Infection with Helicobacter pylori causes extensive gastric epithelial cell inflammation which may progress to atrophic gastritis, intestinal metaplasia, and even gastric adenocarcinoma. Apigenin (4',5,7-trihydroxyflavone) is widely distributed in fruits and vegetables, and is a well-known antiinflammatory supplement with low cytotoxicity. In this study, we investigated the anti-inflammatory effects of apigenin in H. pylori-infected MKN45 cells, for which IκBα, cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), reactive oxygen species (ROS), interleukin-8 (IL-8), IL-6, IL-1β, and mucin-2 (MUC-2) expressions were examined. Apigenin treatments (9.3-74 μM) significantly increased the IκBα expression, and thus inhibited nuclear factor kappa B (NF-κB) activation, and the inflammatory factor (COX-2, ICAM-1, ROS, IL-6, and IL-8) expressions decreased. The ROS levels decreased partially based on the intrinsic scavenging property of apigenin. In summary, apigenin treatments effectively inhibited NF-κB activation and the related inflammatory factor expressions, as well as increased MUC-2 expression in the H. pylori-infected MKN45 cells. The compound shows great potential as a candidate agent for the inhibition of H. pylori-induced extensive gastric epithelial cell inflammation.

  16. Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis.

    PubMed

    Rosillo, María Ángeles; Alcaraz, María José; Sánchez-Hidalgo, Marina; Fernández-Bolaños, José G; Alarcón-de-la-Lastra, Catalina; Ferrándiz, María Luisa

    2014-12-01

    The consumption of extra virgin olive oil (EVOO) in Mediterranean countries has shown beneficial effects. A wide range of evidence indicates that phenolic compounds present in EVOO are endowed with anti-inflammatory properties. In this work, we evaluated the effects of EVOO-polyphenol extract (PE) in a model of rheumatoid arthritis, the collagen-induced arthritis model in mice. On day 0, DBA-1/J mice were immunized with bovine type II collagen. On day 21, mice received a booster injection. PE (100 and 200 mg/kg) was orally administered once a day from days 29 to 41 to arthritic mice. We have demonstrated that PE decreases joint edema, cell migration, cartilage degradation and bone erosion. PE significantly reduced the levels of proinflammatory cytokines and prostaglandin E2 in the joint as well as the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. Our data indicate that PE inhibits c-Jun N-terminal kinase, p38 and signal transducer and activator of transcription-3. In addition, PE decreases nuclear factor κB translocation leading to the down-regulation of the arthritic process. These results support the interest of natural diet components in the development of therapeutic products for arthritic conditions.

  17. A new flavan-3-ol and the anti-inflammatory effect of flavonoids from the fruit peels of Wisteria floribunda.

    PubMed

    Tai, Bui Huu; Trung, Trinh Nam; Nhiem, Nguyen Xuan; Ha, Do Thi; Van Men, Chu; Duong, Vu Binh; Van Luong, Hoang; Song, Seokbean; Bae, Kihwan; Kim, Young Ho

    2011-10-01

    A new flavan-3-ol, (+)-afzelechin 5-O-β-d-glucopyranoside (2), together with 13 known flavonoids (1, 3-14), was isolated from the fruit peels of Wisteria floribunda. Their structures were assigned by detailed interpretation of NMR, MS, and CD spectroscopic data, as well as by comparing with published reports. The in vitro anti-inflammatory activity of the isolated compounds (1-14) was examined. Among them, compounds 3, 6, and 9 produced highest inhibitory effects on tumor necrosis factor alpha (TNF-α)-induced nuclear factor kappa-B activation in HepG2 cells with IC(50) values of 14.1, 16.5, and 11.9 μM, respectively. With the exception of compound 6, the compounds significantly inhibited the accumulation of pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2 proteins in TNF-α-stimulated HepG2 cells at a concentration as low as 0.1 μM.

  18. Morroniside cinnamic acid conjugate as an anti-inflammatory agent.

    PubMed

    Takeda, Yoshinori; Tanigawa, Naomi; Sunghwa, Fortunatus; Ninomiya, Masayuki; Hagiwara, Makoto; Matsushita, Kenji; Koketsu, Mamoru

    2010-08-15

    A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell-cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC(50)=49.3 microM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC(50)=88.2 microM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-alpha-induced E-selectin expression.

  19. Natural anti-inflammatory agents for pain relief

    PubMed Central

    Maroon, Joseph C.; Bost, Jeffrey W.; Maroon, Adara

    2010-01-01

    The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use. PMID:21206541

  20. Anti-inflammatory and immunosuppressive drugs and reproduction

    PubMed Central

    Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

    2006-01-01

    Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

  1. Terpenoids with anti-inflammatory activity from Abies chensiensis.

    PubMed

    Zhao, Qian-Qian; Wang, Shu-Fang; Li, Ya; Song, Qiu-Yan; Gao, Kun

    2016-06-01

    The phytochemical investigation of Abies chensiensis led to the isolation and identification of nine new compounds including eight triterpenoids (1-8) and a new abietane-type diterpene (9), along with three known compounds (10-12). The absolute configuration of 9 was assigned by X-ray diffraction analysis. Compounds 1-11 were evaluated for the anti-inflammatory activity. Among the tested compounds, 1, 2, 5 and 6 exhibited potent inhibitory activity with IC50 values of 15.97, 18.73, 20.18 and 10.97μM, respectively.

  2. Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics.

    PubMed

    Willson, Douglas F

    2015-06-01

    Drug delivery by aerosol may have several advantages over other modes, particularly if the lung is the target organ. Aerosol delivery may allow achievement of higher concentrations while minimizing systemic effects and offers convenience, rapid onset of action, and avoidance of the needles and sterile technique necessary with intravenous drug administration. Aerosol delivery may change the pharmacokinetics of many drugs, however, and an awareness of the caveats of aerosolized drug delivery is mandatory to ensure both safety and adequate drug delivery. This paper discusses the administration of surfactants, anti-inflammatory agents, and analgesics by the aerosol route.

  3. Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

    PubMed Central

    Elena, Talero; Rosanna, Di Paola; Emanuela, Mazzon; Esposito, Emanuela; Virginia, Motilva; Salvatore, Cuzzocrea

    2012-01-01

    Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors. PMID:22685374

  4. The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct.

    PubMed

    Choe, In-Hu; Jeon, Hyeon Jin; Eom, Sung-Hwan; Han, Young-Ki; Kim, Yoon Sook; Lee, Sang-Hoon

    2016-06-15

    In this study, flatfish byproducts were hydrolyzed by Protamex at high hydrostatic pressure and glycosylated with ribose to utilize the protein of flatfish byproducts as a nutraceutical. We investigated the anti-inflammatory effects of glycosylated fish byproduct protein hydrolysate (GFPH) and its anti-inflammatory mechanisms were elucidated in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophage. The results showed that GFPH suppresses LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently. The enzyme-linked immunosorbent assay (ELISA) kit clearly demonstrated that GFPH significantly reduced the production of pro-inflammatory cytokines such as, interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1. Moreover, GFPH reduced nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. These results indicate that the inhibitory effects of GFPH on LPS-induced NO and PGE2 production might be due to the suppression of the NF-κB and MAPKs signaling pathways. Therefore, these results suggest that flatfish byproducts are latent bioactive resources and GFPH may have potential as a therapeutic agent in the treatment of various inflammatory diseases.

  5. Anti-inflammatory effect of procyanidins from wild grape (Vitis amurensis) seeds in LPS-induced RAW 264.7 cells.

    PubMed

    Bak, Min-Ji; Truong, Van Long; Kang, Hey-Sook; Jun, Mira; Jeong, Woo-Sik

    2013-01-01

    In the present study, the anti-inflammatory effect and underlying mechanisms of wild grape seeds procyanidins (WGP) were examined using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells. We used nitric oxide (NO) and prostaglandin E2 (PGE2) and reactive oxygen species (ROS) assays to examine inhibitory effect of WGP and further investigated the mechanisms of WGP suppressed LPS-mediated genes and upstream expression by Western blot and confocal microscopy analysis. Our data indicate that WGP significantly reduced NO, PGE2, and ROS production and also inhibited the expression of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions. Consistently, WGP significantly reduced LPS-stimulated expression of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin- (IL-) 1 β . Moreover, WGP prevented nuclear translocation of nuclear factor- κ B (NF κ B) p65 subunit by reducing inhibitory κ B- α (I κ B α) and NF κ B phosphorylation. Furthermore, we found that WGP inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, our results demonstrated that WGP exerts potent anti-inflammatory activity through the inhibition of iNOS and COX-2 by regulating NF κ B and p38 MAPK pathway.

  6. Induction of heme oxygenase-1 mediates the anti-inflammatory effects of the ethanol extract of Rubus coreanus in murine macrophages.

    PubMed

    Park, Jun Hong; Oh, Sun-Mee; Lim, Soon Sung; Lee, Yeon Sil; Shin, Hyun-Kyung; Oh, Yang-Seok; Choe, Nong-Hoon; Park, Jung Han Yoon; Kim, Jin-Kyung

    2006-12-08

    Foods of plant origin, especially fruits and vegetables, draw increased attention because of their potential benefits to human health. The aim of the present study was to determine in vitro anti-inflammatory activity of four different extracts obtained from the fruits of Rubus coreanus (aqueous and ethanol extracts of unripe and ripe fruits). Among the four extracts, the ethanol extract of unripe fruits of R. coreanus (URCE) suppressed nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. We also demonstrated that URCE by itself is a potent inducer of heme oxygenase-1 (HO-1). Inhibition of HO-1 activity by tin protoporphyrin, a specific HO-1 inhibitor, suppressed the URCE-induced reductions in the production of NO and PGE(2) as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Our data suggest that URCE exerts anti-inflammatory effects in macrophages via activation of the HO-1 pathway and helps to elucidate the mechanism underlying the potential therapeutic value of R. coreanus extracts.

  7. Anti-inflammatory activity of the active components from the roots of Cosmos bipinnatus in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    PubMed

    Sohn, Sang-Hyun; Yun, Bong-Sik; Kim, So-Young; Choi, Wahn-Soo; Jeon, Hyun-Soo; Yoo, Jun-Sik; Kim, Si-Kwan

    2013-01-01

    We isolated a sesquiterpene lactone from the methanol extract of the roots of Cosmos bipinnatus, namely, MDI (a mixture of dihydrocallitrisin and isohelenin). The anti-inflammatory activity of MDI was evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. MDI significantly inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2. Consistent with these results, the production of NO and prostaglandin E2 (PGE2) was suggested to be suppressed by MDI in a concentration-dependent manner (IC50 value was 0.94 and 2.88 µg mL(-1) for NO and PGE2, respectively). In addition, MDI significantly inhibited the expressions of pro-inflammatory cytokines such as IL-1β, IL-6, IFN-γ and TNF-α. Furthermore, MDI attenuated DNA-binding activity of NF-κB by inhibiting the phosphorylation of IκB. These results indicate that MDI isolated from the roots of C. bipinnatus shows anti-inflammatory activity in LPS-stimulated murine macrophages by modulating the NF-κB pathway.

  8. New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.

    PubMed

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Lee, Chang-Min; Choi, Yung Hyun; Lee, Hak-Ju; Choi, Il-Whan; Kim, Gi-Young

    2015-01-01

    Microglia are main immune cells to exacerbate neural disorders in persistent overactivating. Therefore, it is a good strategy to regulate microglia for the treatment of neural disorders. In the present study, we isolated and characterized a novel compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton (5-DRL) from Clematis mandshurica, and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-treated BV2 microglial cells. 5-DRL inhibited the expression of LPS-stimulated proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as their regulatory genes inducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2). 5-DRL also downregulated the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of the nuclear translocation of the NF-κB subunits, p65 and p50. Consistent with the inhibition of iNOS and COX-2 via NF-κB activity with 5-DRL, an inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), also led to the suppression of LPS-induced iNOS and COX-2 expression. Additionally, 5-DRL corresponding with antioxidants, N-acetylcysteine (NAC) and glutathione (GSH), remarkably inhibited reactive oxygen species (ROS) generation. Both NAC and GSH, thus attenuated the expression of iNOS and COX-2 by suppressing NF-κB activation, indicating that 5-DRL suppresses LPS-induced iNOS and COX-2 expression through downregulation of the ROS-dependent NF-κB signaling pathway. The present study also indicated that 5-DRL suppresses NO and PGE2 production by inducing heme oxygenase-1 (HO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, the present data indicate that 5-DRL attenuates the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting ROS-dependent NF-κB activation and stimulating the Nrf2/HO-1 signal pathway. These data may be implicated in the application of 5-DRL in LPS

  9. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models

    PubMed Central

    Bang, Jun Soo; Oh, Da Hee; Choi, Hyun Mi; Sur, Bong-Jun; Lim, Sung-Jig; Kim, Jung Yeon; Yang, Hyung-In; Yoo, Myung Chul; Hahm, Dae-Hyun; Kim, Kyoung Soo

    2009-01-01

    Introduction The objective of this study was to determine the anti-inflammatory, nociceptive, and antiarthritic effects of piperine, the active phenolic component in black pepper extract. Methods The in vitro anti-inflammatory activity of piperine was tested on interleukin 1β (IL1β)-stimulated fibroblast-like synoviocytes derived form patients with rheumatoid arthritis. The levels of IL6, matrix metalloproteinase (MMPs), cyclo-oxygenase 2 (COX-2), and prostaglandin E2 (PGE2) were investigated by ELISA and RT-PCR analysis. The analgesic and antiarthritic activities of piperine were investigated on rat models of carrageenan-induced acute paw pain and arthritis. The former were evaluated with a paw pressure test, and the latter by measuring the squeaking score, paw volume, and weight distribution ratio. Piperine was administrated orally to rats at 20 and 100 mg/kg/day for 8 days. Results Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE2 in a dose dependant manner at concentrations of 10 to 100 μg/ml. In particular, the production of PGE2 was significantly inhibited even at 10 μg/ml of piperine. Piperine inhibited the migration of activator protein 1 (AP-1), but not nuclear factor (NF)κB, into the nucleus in IL1β-treated synoviocytes. In rats, piperine significantly reduced nociceptive and arthritic symptoms at days 8 and 4, respectively. Histological staining showed that piperine significantly reduced the inflammatory area in the ankle joints. Conclusions These results suggest that piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Thus, piperine should be further studied with regard to use either as a pharmaceutical or as a dietary supplement for the treatment of arthritis. PMID:19327174

  10. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats

    PubMed Central

    Mansouri, Mohammad Taghi; Hemmati, Ali Asghar; Naghizadeh, Bahareh; Mard, Seyyed Ali; Rezaie, Anahita; Ghorbanzadeh, Behnam

    2015-01-01

    Objectives: Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA. Materials and Methods: Carrageenan-induced mouse paw edema model was used for induction of inflammation. Results: The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E2 (PGE2) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1–30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26–14.76) mg/kg. It decreased the serum concentration of NO, PGE2, aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin. Conclusions: Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE2 overproduction. PMID:26069367

  11. The Anti-inflammatory Effect of the CXCR4 Antagonist-N15P Peptide and Its Modulation on Inflammation-Associated Mediators in LPS-Induced PBMC.

    PubMed

    Mo, Xue-mei; Sun, Han-xiao

    2015-01-01

    Inflammation was the important pathological process of many disease developments, but current therapeutic means for inflammatory diseases are not satisfactory. Chemokines and their receptors represent valuable targets for anti-inflammatory drug discovery. The N15P polypeptide (sequence: LGASWHRPDKCCLGY) is independently developed by our research group, it is a new CXCR4 antagonist drug derived from viral macrophage inflammatory protein-II (vMIP-II). This study aims to clarify the anti-inflammatory potency of N15P polypeptide on the lipopolysaccharide (LPS)-induced inflammation in vitro. In this study, we evaluated the anti-inflammatory effects of N15P polypeptide by the LPS-induced peripheral blood mononuclear cell (PBMC) model and measured the level of inflammatory factors (tumor necrosis factor alpha (TNF-α), IL-6, IL-8, nuclear factor kappaB (NF-κB), cyclooxygenase-2 (COX-2), Toll-like receptor 4 (TLR4), MyD88, phosphoinositide 3-kinase (PI3K), and Akt). The messenger RNA (mRNA) expressions of inflammatory factors were analyzed by real-time PCR (RT-PCR) microarray analysis, and the production of inflammatory factors was measured further by enzyme-linked immunosorbent assay (ELISA) and Western blot. The results showed that the expression of inflammatory factors (TNF-α, IL-6, IL-8, NF-κB, COX-2, TLR4, MyD88, PI3K, and Akt) was downregulated by N15P peptide, suggesting that N15P peptide has a strong inhibitory effect on the inflammatory responses induced by LPS.

  12. Anti-inflammatory strategies in the treatment of schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half.

  13. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  14. 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.

  15. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    NASA Astrophysics Data System (ADS)

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-11-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

  16. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid

    PubMed Central

    Haj, Christeene G.; Sumariwalla, Percy F.; Hanuš, Lumír; Kogan, Natalya M.; Yektin, Zhana; Feldmann, Mark

    2015-01-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ9-tetrahydrocannabinol (Δ9-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ9-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ9-THC–like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ9-THC–like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID:26272937

  17. Pharmacokinetics and dosage regimens of anti-inflammatory drugs.

    PubMed

    Lees, P; May, S A; White, D

    1990-01-01

    The term anti-inflammatory drug, in its broadest sense, encompasses a number of very diverse compounds, ranging from steroids to non-steroidal anti-inflammatory drugs (NSAIDs) and from disease modifying agents (used in the treatment of canine rheumatoid arthritis) to chondroprotective agents (used in the treatment of osteoarthrosis and traumatic arthritis in the horse). For many of these drugs (eg, chondroprotective and disease modifying agents) the mode of action is unknown and even with steroids and NSAIDs there is no universal agreement on mechanism of action. It is therefore in many cases impossible to link pharmacokinetic data to a drug's pharmacodynamics, for example to an effect on a specific biochemical marker. Some agents, including corticosteroids, may have indirect modes of action, so that the pharmacodynamic half-life can be much longer than (and not clearly related to) the pharmacokinetic half-life. In other cases, clinical benefits may only become apparent after several weeks or even months. It can therefore be difficult or impossible to use classical pharmacokinetic approaches to set dosing intervals and dose rates for clinical use. To some extent, the position is more straightforward with NSAIDs. However, even with these drugs simple approaches are not possible and this paper will review briefly some of the studies undertaken in our laboratory which have attempted to utilize NSAID kinetics to set dosage schedules for clinical use.

  18. Oncostatin M in the anti-inflammatory response

    PubMed Central

    Wahl, A; Wallace, P

    2001-01-01

    Oncostatin M (OM) is a pleiotropic cytokine of the interleukin 6 family, whose in vivo properties and physiological function remain in dispute and poorly defined. These in vivo studies strongly suggest that OM is anabolic, promoting wound healing and bone formation, and anti-inflammatory. In models of inflammation OM is produced late in the cytokine response and protects from lipopolysaccharide (LPS)-induced toxicities, promoting the re-establishment of homoeostasis by cooperating with proinflammatory cytokines and acute phase molecules to alter and attenuate the inflammatory response. Administration of OM inhibited bacterial LPS-induced production of tumour necrosis factor α and septic lethality in a dose dependent manner. Consistent with these findings, in animal models of chronic inflammatory disease OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and antibody production were not impaired by OM treatment. Taken together, these data indicate that the activities of this cytokine in vivo are anti-inflammatory without concordant immunosuppression.

 PMID:11890661

  19. Anti-inflammatory activity of natural dietary flavonoids.

    PubMed

    Pan, Min-Hsiung; Lai, Ching-Shu; Ho, Chi-Tang

    2010-10-01

    Over the past few decades, inflammation has been recognized as a major risk factor for various human diseases. Acute inflammation is short-term, self-limiting and it's easy for host defenses to return the body to homeostasis. Chronic inflammatory responses are predispose to a pathological progression of chronic illnesses characterized by infiltration of inflammatory cells, excessive production of cytokines, dysregulation of cellular signaling and loss of barrier function. Targeting reduction of chronic inflammation is a beneficial strategy to combat several human diseases. Flavonoids are widely present in the average diet in such foods as fruits and vegetables, and have been demonstrated to exhibit a broad spectrum of biological activities for human health including an anti-inflammatory property. Numerous studies have proposed that flavonoids act through a variety mechanisms to prevent and attenuate inflammatory responses and serve as possible cardioprotective, neuroprotective and chemopreventive agents. In this review, we summarize current knowledge and underlying mechanisms on anti-inflammatory activities of flavonoids and their implicated effects in the development of various chronic inflammatory diseases.

  20. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials

    PubMed Central

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-01-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24724793

  1. Heme oxygenase-1 and anti-inflammatory M2 macrophages.

    PubMed

    Naito, Yuji; Takagi, Tomohisa; Higashimura, Yasuki

    2014-12-15

    Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin. HO-1, a stress-inducible protein, is induced by various oxidative and inflammatory signals. Consequently, HO-1 expression has been regarded as an adaptive cellular response against inflammatory response and oxidative injury. Although several transcriptional factors and signaling cascades are involved in HO-1 regulation, the two main pathways of Nrf2/Bach1 system and IL-10/HO-1 axis exist in monocyte/macrophage. Macrophages are broadly divisible into two groups: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. More recently, several novel macrophage subsets have been identified including Mhem, Mox, and M4 macrophages. Of these, M2 macrophages, Mhem, and Mox are HO-1 highly expressing macrophages. HO-1 has been recognized as having major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 deficient mice and human cases of genetic HO-1 deficiency. However, the mechanism underlying the immunomodulatory actions of HO-1 remains poorly defined. This review specifically addresses macrophage polarization. The present current evidence indicates that HO-1 induction mediated by multiple pathways can drive the phenotypic shift to M2 macrophages and suggests that HO-1 induction in macrophages is a potential therapeutic approach to immunomodulation in widely diverse human diseases.

  2. Potential anti-inflammatory actions of the elmiric (lipoamino) acids

    PubMed Central

    Burstein, Sumner H.; Adams, Jeffrey K.; Bradshaw, Heather B.; Fraioli, Cristian; Rossetti, Ronald G.; Salmonsen, Rebecca A.; Shaw, John W.; Walker, J. Michael; Zipkin, Robert E.; Zurier, Robert B.

    2007-01-01

    A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells was the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them. PMID:17383881

  3. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    PubMed

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.

  4. Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris.

    PubMed

    Chiu, Ching-Peng; Liu, Shan-Chi; Tang, Chih-Hsin; Chan, You; El-Shazly, Mohamed; Lee, Chia-Lin; Du, Ying-Chi; Wu, Tung-Ying; Chang, Fang-Rong; Wu, Yang-Chang

    2016-02-24

    Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of C. militaris was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of C. militaris fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (1), the new cerebroside, along with soyacerebroside I (2) and glucocerebroside (3) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM.

  5. Anti-inflammatory and antinociceptive activity of Urera aurantiaca.

    PubMed

    Riedel, R; Marrassini, C; Anesini, C; Gorzalczany, S

    2015-01-01

    Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti-inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti-inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan-induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose-dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis 3-ethylbenzothiazoline 6-sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50 : 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity.

  6. Structural basis of the anti-inflammatory activity of melatonin.

    PubMed

    de la Rocha, Nadir; Rotelli, Alejandra; Aguilar, Carlos F; Pelzer, Lilian

    2007-01-01

    The anti-inflammatory activity of melatonin (CAS 73-31-4) was examined, using the rat paw edema model, and compared with the non-steroidal anti-inflammatory drug (NSAID) indometacin (CAS 53-86-1) which exerts its effects by inhibition of prostaglandin production on acute inflammation. The experiments showed that melatonin has an important effect on acute inflammatory processes acting as an inhibitor in a similar manner to indometacin. The structural interactions of melatonin with cyclooxygenase (COX), the pharmacological target of NSAIDs, were investigated using computer graphics applications. The results indicated that melatonin has an excellent steric and electronic complementarity with COX. It was found, similarly to previously studied crystal structures of protein-inhibitor complexes, that almost all interactions were of the hydrophobic type but for the typical carboxylate or electronegative group interaction, at the mouth of the active site channel, with Arg 120 and Tyr 355. Therefore, it seems possible that melatonin might bind to the active site of COX-1 and COX-2 suggesting that it may act as a natural inhibitor of the functions of cyclooxygenase modulating in a natural manner the activity of this enzyme.

  7. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    PubMed Central

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-01-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies. PMID:26584637

  8. An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs

    PubMed Central

    Ong, C.K.S.; Lirk, P.; Tan, C.H.; Seymour, R.A.

    2007-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX pathway in the generation of inflammation and in the biochemical recognition of pain. This group of drugs has recently come under scrutiny because of recent focus in the literature on the various adverse effects that can occur when applying NSAIDs. This review will provide an educational update on the current evidence of the efficacy and adverse effects of NSAIDs. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are the effective therapeutic approaches that could reduce the adverse effects of NSAIDs. Finally, an algorithm is proposed which delineates a general decision-making tree to select the most appropriate analgesic for an individual patient based on the evidence reviewed. PMID:17456832

  9. Degradable magnesium-based implant materials with anti-inflammatory activity.

    PubMed

    Peng, Qiuming; Li, Kun; Han, Zengsheng; Wang, Erde; Xu, Zhigang; Liu, Riping; Tian, Yongjun

    2013-07-01

    The objective of this study was to prepare a new biodegradable Mg-based biomaterial, which provides good mechanical integrity in combination with anti-inflammatory function during the degradation process. The silver element was used, because it improved the mechanical properties as an effective grain refiner and it is also treated as a potential anti-inflammatory core. The new degradable Mg-Zn-Ag biomaterial was prepared by zone solidification technology and extrusion. The mechanical properties were mostly enhanced by fine grain strengthening. In addition, the alloys exhibited good cytocompatibility. The anti-inflammatory function of degradation products was identified by both interleukin-1α and nitric oxide modes. The anti-inflammatory impact was significantly associated with the concentration of silver ion. It was demonstrated that Mg-Zn-Ag system was a potential metallic stent with anti-inflammatory function, which can reduce the long-term dependence of anti-inflammatory drug after coronary stent implantation.

  10. Synthesis, Photophysical and Photochemical Properties of a Set of Silicon Phthalocyanines Bearing Anti-Inflammatory Groups.

    PubMed

    Şahin, Belgin; Topal, Sevinc Zehra; Atilla, Devrim

    2017-01-01

    In this study, a series of novel silicon (IV) phthalocyanines conjugated axially with anti-inflammatory (sulindac) and triethylene glycol groups has been synthesized. Different synthetic strategies were attempted to obtain the targeted molecules in high yield. The compounds were fully characterized by using different analyses techniques. Our objectives were to generate a system with sulindac group which enhances the singlet oxygen generation and exhibits anti-cancer effect. Therefore, photophysical and photochemical properties of these compounds were investigated in different solvents. The substituent effect on fluorescence quantum yield and singlet oxygen generation was evaluated for efficiency in photodynamic therapy (PDT) as photosensitizer. The molecules exhibited no aggregation tendency, solubility in common organic solvents, high singlet oxygen quantum yield and high photostability in DMSO so these favourable properties make them good candidates as photosensitizer for PDT. In addition, their stabilities were investigated in DMSO, THF, acetonitrile and DMF.

  11. Stereoselective synthesis and anti-inflammatory activities of 6- and 7-membered dioxacycloalkanes.

    PubMed

    Gu, Keli; Bi, Lanrong; Zhao, Ming; Wang, Chao; Dolan, Cheryl; Kao, Michael C; Tok, Jeffrey B-H; Peng, Shiqi

    2006-03-01

    A class of 5-trifluoroacetylamino-1,3-dioxacycloalkanes, 5-benzoylamino-1,3-dioxacycloalkanes, and 5-amino-1,3-dioxacycloalkane compounds were stereoselectively synthesized as potential anti-inflammatory drug candidates. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model, from which multiple compounds possessing anti-inflammatory properties which surpass aspirin were identified; these compounds were then compared to establish structure-activity relationships.

  12. Topical anti-inflammatory activity of pinda thailam, a herbal gel formulation.

    PubMed

    Periyanayagam, K; Venkatarathnakumar, T; Nagaveni, A; Subitha, V G; Sundari, P; Vaijorohini, M; Umamaheswari, V

    2004-07-01

    The present study aims to evaluate the topical anti-inflammatory activity of "Pinda thailam", a herbal gel formulation containing aqueous extract of roots of Rubia cordifolia (Rubiaceae) and Hemidesmus indicus (Asclepiadaceae) which are known for their anti-inflammatory activity using the technique of carrageenin induced paw oedema in albino rats. The herbal gel formulation showed significant anti-inflammatory activity comparable to the reference standard Diclofenac sodium gel.

  13. N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acids: their synthesis, anti-inflammatory evaluation and QSAR analysis.

    PubMed

    Li, Xiangmin; Zhao, Ming; Tang, Yu-Rong; Wang, Chao; Zhang, Ziding; Peng, Shiqi

    2008-01-01

    Developing novel anti-inflammatory drugs is increasingly important in modern pharmaceutical industry. In this work, the reactions of both amino acids and their methylesters with 3-(5,5-dimethyl-1,3-dioxane-2-yl)propanal (2) were performed to either directly provide the goal products N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acids (4a-s) in 9-65% yields or provide the intermediates N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acid methylesters (3a-s) in 78-87% yields. The saponification of 3a-s provided 4a-s in 80-89% yields. Using a xylene-induced ear edema model, the anti-inflammatory activities of these newly synthesized anti-inflammatory agents were evaluated. The results indicated that comparing to the vehicle control 17 out of 4a-s significantly inhibited the development of inflammation in mice (p<0.01). In particular, eight out of 4a-s exhibited an even higher anti-inflammatory activity than the standard reference drug aspirin (p<0.05-0.01). A QSAR analysis was performed by use of the molecular descriptors generated from e-dragon software. The predictive accuracy of the established QSAR model implies that it may be promising for screening the new derivatives of 2-position amino acid substituted 1,3-dioxanes as potential anti-inflammatory agents.

  14. Multidimensional preparative liquid chromatography to isolate flavonoids from bergamot juice and evaluation of their anti-inflammatory potential.

    PubMed

    Russo, Marina; Dugo, Paola; Marzocco, Stefania; Inferrera, Veronica; Mondello, Luigi

    2015-12-01

    Important objectives of a high-performance liquid chromatography preparative process are: purity of products isolated, yield, and throughput. The multidimensional preparative liquid chromatography method used in this work was developed mainly to increase the throughput; moreover purity and yield are increased thanks to the automated collection of the molecules based on the intensity of a signal generated from the mass spectrometer detector, in this way only a specific product can be targeted. This preparative system allowed, in few analyses both in the first and second dimensions, the isolation of eight pure compounds present at very different concentration in the original sample with high purity (>95%) and yield, which showed how the system is efficient and versatile. Pure molecules were used to validate the analytical method and to test the anti-inflammatory and antiproliferative potential of flavonoids. The contemporary presence, in bergamot juice, of all the flavonoids together increases the anti-inflammatory effect with respect to the single compound alone.

  15. Anti-inflammatory and antifibrotic effects of methyl palmitate

    SciTech Connect

    El-Demerdash, Ebtehal

    2011-08-01

    Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-{alpha} and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (I{kappa}B{alpha}) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-{kappa}B, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research Highlights: >Methyl palmitate is a universal macrophage inhibitor. >It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. >The underlying mechanism of these effects could be through NF-kB inhibition.

  16. New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

    PubMed Central

    Bano, Saira; Wahab, Atia-tul-; Yousuf, Sammer; Jabeen, Almas; Mesaik, Mohammad Ahmed; Rahman, Atta-ur-; Choudhary, M. Iqbal

    2016-01-01

    Microbial transformation of the anti-inflammatory steroid medrysone (1) was carried out for the first time with the filamentous fungi Cunninghamella blakesleeana (ATCC 8688a), Neurospora crassa (ATCC 18419), and Rhizopus stolonifer (TSY 0471). The objective was to evaluate the anti-inflammatory potential of the substrate (1) and its metabolites. This yielded seven new metabolites, 14α-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (2), 6β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (3), 15β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (4), 6β,17α-dihydroxy-6α-methylpregn-4-ene-3,11,20-trione (5), 6β,20S-dihydroxy-6α-methylpregn-4-ene-3,11-dione (6), 11β,16β-dihydroxy-6α-methylpregn-4-ene-3,11-dione (7), and 15β,20R-dihydroxy-6α-methylpregn-4-ene-3,11-dione (8). Single-crystal X-ray diffraction technique unambiguously established the structures of the metabolites 2, 4, 6, and 8. Fungal transformation of 1 yielded oxidation at the C-6β, -11β, -14α, -15β, -16β positions. Various cellular anti-inflammatory assays, including inhibition of phagocyte oxidative burst, T-cell proliferation, and cytokine were performed. Among all the tested compounds, metabolite 6 (IC50 = 30.3 μg/mL) moderately inhibited the reactive oxygen species (ROS) produced from zymosan-induced human whole blood cells. Compounds 1, 4, 5, 7, and 8 strongly inhibited the proliferation of T-cells with IC50 values between <0.2–10.4 μg/mL. Compound 7 was found to be the most potent inhibitor (IC50 < 0.2 μg/mL), whereas compounds 2, 3, and 6 showed moderate levels of inhibition (IC50 = 14.6–20.0 μg/mL). Compounds 1, and 7 also inhibited the production of pro-inflammatory cytokine TNF-α. All these compounds were found to be non-toxic to 3T3 cells (mouse fibroblast), and also showed no activity when tested against HeLa (human epithelial carcinoma), or against PC3 (prostate cancer) cancer cell lines. PMID:27104348

  17. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

    PubMed Central

    Cameron, Amy R.; Morrison, Vicky L.; Levin, Daniel; Mohan, Mohapradeep; Forteath, Calum; Beall, Craig; McNeilly, Alison D.; Balfour, David J.K.; Savinko, Terhi; Wong, Aaron K.F.; Viollet, Benoit; Sakamoto, Kei; Fagerholm, Susanna C.; Foretz, Marc

    2016-01-01

    Rationale: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood. Objective: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties. Methods and Results: In primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α–dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2). Metformin suppressed IKKα/β activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation. Equally AMP-activated protein kinase was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages, metformin specifically blunted secretion of proinflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naive diabetes mellitus population cohort, we observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy. Compared with sulfonylurea exposure, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8 to 16 months by 0.09 U (95% confidence interval, 0.02–0.17; P=0.013) and increased the likelihood that neutrophil to lymphocyte ratio would be lower than baseline after 8 to 16 months (odds ratio, 1.83; 95% confidence interval, 1.22–2.75; P=0.00364). Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging

  18. Anti-inflammatory effects of diethylcarbamazine: a review.

    PubMed

    Peixoto, Christina Alves; Silva, Bruna Santos

    2014-07-05

    Diethylcarbamazine (DEC) interferes with cyclooxygenase and lipoxygenase pathways, reducing the production of thromboxane, prostacyclin, prostaglandin and leukotrienes. Recent studies using different experimental models of inflammation have indicated that DEC, in addition to inhibiting cyclooxygenase and lipoxygenase pathways, also inhibits nuclear transcription factor kappa B (NF-κB) activation, which is a key regulator of proinflammatory genes such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS) and even cyclooxygenase 2 (COX-2). The aim of the present study is to provide a comprehensive summary of DEC, including a description of filaricidal action, inhibition of synthesis and secretory pathways, immunomodulatory activity, and specific inhibition of lipoxygenase and cyclooxygenase pathways.

  19. The Anti-Inflammatory and Vasodilating Effects of Three Selected Dietary Organic Sulfur Compounds from Allium Species

    PubMed Central

    Chu, Chin-Chen; Wu, Wen-Shiann; Shieh, Ja-Ping; Chu, Heuy-Ling; Lee, Chia-Pu; Duh, Pin-Der

    2017-01-01

    The anti-inflammatory and vasodilating effects of three selected dietary organic sulfur compounds (OSC), including diallyl disulfide (DADS), dimethyl disulfide (DMDS), and propyl disulfide (PDS), from Allium species were investigated. In the anti-inflammatory activity assay, the three OSC demonstrated significant inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-induced RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in activated RAW 264.7 cells was inhibited by the three OSC, indicating that the three OSC prevented the LPS-induced inflammatory response in RAW 264.7 cells. For the vasodilative assay, the three OSC were ineffective in producing NO in SVEC4-10 cells, but they did enhance prostacyclin (PGI2) production. The expression of COX-2 in SVEC4-10 cells was activated by DADS and DMDS. Pretreatment of SVEC4-10 cells with the three OSC decreased ROS generation in H2O2-induced SVEC4-10 cells. In addition, the three OSC significantly inhibited angiotensin-I converting enzyme (ACE). The up-regulation of PGI2 production and COX-2 expression by DADS and DMDS and the reduction of ROS generation by DADS, DMDS, and PDS in SVEC4-10 cells contributed to the vasodilative effect of the three OSC. Collectively, these findings suggest that DADS, DMDS, and PDS are potential anti-inflammatory and vasodilative mediators. PMID:28134777

  20. 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.

  1. Synthesis, characterization, evaluation and molecular dynamics studies of 5, 6-diphenyl-1,2,4-triazin-3(2H)-one derivatives bearing 5-substituted 1,3,4-oxadiazole as potential anti-inflammatory and analgesic agents.

    PubMed

    Banerjee, Anupam G; Das, Nirupam; Shengule, Sushant A; Srivastava, Radhey Shyam; Shrivastava, Sushant Kumar

    2015-08-28

    A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in acute, sub-chronic and chronic animal models of inflammation. Derivatives 4d, 4e, 4g, 4j and 4l exhibited significant anti-inflammatory activity with reduced ulcerogenic, hepatotoxic and renotoxic liabilities compared to standard indomethacin. These potential derivatives were also evaluated for in vivo analgesic activity using a writhing model and the formalin-induced paw licking response in mice. Compounds 4d, 4e and 4g exhibited comparable analgesic activity, whereas 4j and 4l yielded moderate effects. The specificity of compounds 4d, 4e, 4g, 4j, and 4l to inhibit (cyclooxygenase-1) COX-1 and (cyclooxygenase-2) COX-2 isozymes and their kinetics were also determined via an in vitro COX inhibition assay. In silico docking studies were performed using a molecular dynamics simulation of the most active compound 4d (COX-2 IC50: 3.07 μM) at the COX-2 active site. The outcome of this exercise helped to verify the consensual interaction of these compounds with the enzyme.

  2. Kainic acid-induced neurodegeneration and activation of inflammatory processes in organotypic hippocampal slice cultures: treatment with cyclooxygenase-2 inhibitor does not prevent neuronal death.

    PubMed

    Järvelä, Juha T; Ruohonen, Saku; Kukko-Lukjanov, Tiina-Kaisa; Plysjuk, Anna; Lopez-Picon, Francisco R; Holopainen, Irma E

    2011-06-01

    In the postnatal rodent hippocampus status epilepticus (SE) leads to age- and region-specific excitotoxic neuronal damage, the precise mechanisms of which are still incompletely known. Recent studies suggest that the activation of inflammatory responses together with glial cell reactivity highly contribute to excitotoxic neuronal damage. However, pharmacological tools to attenuate their activation in the postnatal brain are still poorly elucidated. In this study, we investigated the role of inflammatory mediators in kainic acid (KA)-induced neuronal damage in organotypic hippocampal slice cultures (OHCs). A specific cyclooxygenase-2 (COX-2) inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) was used to study whether or not it could ameliorate neuronal death. Our results show that KA treatment (24 h) resulted in a dose-dependent degeneration of CA3a/b pyramidal neurons. Furthermore, COX-2 immunoreactivity was pronouncedly enhanced particularly in CA3c pyramidal neurons, microglial and astrocyte morphology changed from a resting to active appearance, the expression of the microglial specific protein, Iba1, increased, and prostaglandin E₂ (PGE₂) production increased. These indicated the activation of inflammatory processes. However, the expression of neither proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), nor the anti-inflammatory cytokine IL-10 mRNA was significantly altered by KA treatment as studied by real-time PCR. Despite activation of an array of inflammatory processes, neuronal damage could not be rescued either with the combined pre- and co-treatment with a specific COX-2 inhibitor, NS-398. Our results suggest that KA induces activation of a repertoire of inflammatory processes in immature OHCs, and that the timing of anti-inflammatory treatment to achieve neuroprotection is a challenge due to developmental properties and the complexity of inflammatory processes activated by

  3. New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges.

    PubMed

    Naglah, Ahmed M; Ahmed, Atallah F; Wen, Zhi-Hong; Al-Omar, Mohamed A; Amr, Abd El-Galil E; Kalmouch, Atef

    2016-04-15

    A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a-c. The chemical structures of the new Schiff bases (5b and 5d-h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%-42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition) at the same concentration (10 μM). The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a-c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents.

  4. An aqueous extract of Ilex paraguariensis reduces carrageenan-induced edema and inhibits the expression of cyclooxygenase-2 and inducible nitric oxide synthase in animal models of inflammation.

    PubMed

    Schinella, Guillermo; Neyret, Elisa; Cónsole, Gloria; Tournier, Horacio; Prieto, José M; Ríos, José-Luis; Giner, Rosa María

    2014-08-01

    Mate (Ilex paraguariensis) is a highly popular herbal beverage in South America due to its high content of caffeine. Its hypolipidemic and antioxidant properties are of increasing interest in the treatment of cardiovascular disorders and for weight control. In the present study, we show for the first time both the local and systemic anti-inflammatory effects of an aqueous extract of mate in three classic in vivo models, namely acute and chronic 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema and acute carrageenan-induced mouse paw edema. Caffeine, rutin, chlorogenic acid, 3,5-dicafeoyl quinic acid, and 4,5-dicafeoyl quinic acid, accompanied by a complex mixture of other simple phenolic acids, were identified in the extract by HPLC-UV analyses. In the acute edema model, mate extract applied topically (1 mg/ear) halved the 12-O-tetradecanoylphorbol 13-acetate-induced acute edema (50 %) and almost suppressed neutrophil infiltration (93 %), while in the 12-O-tetradecanoylphorbol 13-acetate-induced subchronic inflammation, the edema was significantly reduced by 62 % (1 mg/ear/day × seven doses). The oral administration of the mate extract (250 mg/kg) significantly reduced the carrageenan-induced edema at all time points, an effect which was accompanied by a 43 % and 53 % reduction of the expression of cyclooxygenase-2 and inducible nitric oxide synthase, respectively. Histological analyses confirmed a reduction of epithelium thickness, dermis with mild inflammation, hair follicles with some secretory cells of sebaceous glands, and hypodermic adipocytes. In conclusion, mate is endowed with in vivo preventative or therapeutic anti-inflammatory effects in both local and systemic inflammatory processes.

  5. Progestin treatment does not affect expression of cytokines, steroid receptors, oxytocin receptor, and cyclooxygenase 2 in fetal membranes and endometrium from pony mares at parturition.

    PubMed

    Palm, F; Walter, I; Nowotny, N; Budik, S; Helmreich, M; Aurich, C

    2013-01-01

    In most mammalian species, progestins have a major function in maintaining pregnancy. In humans, the physiologic initiation of parturition bears similarities with inflammatory processes and anti-inflammatory effects of progestins have been suggested to postpone birth until term. To examine if comparable effects exist in the horse, mares were treated with the synthetic progestin altrenogest from day 280 of gestation until parturition (N = 5) or were left untreated as controls (N = 7). Tissue from the amnion (AMN), allantochorion (AC), and endometrium (EM) was collected at foaling and mRNA expression of interleukin (IL)-6 and -8, cyclooxygenase 2 (COX2), estrogen receptor (ER) α, progesterone receptor, and oxytocin receptor (OTR) was analyzed. Leukocytes, steroid receptors, COX2, and OTR were also investigated by histology and immunohistochemistry. Expression of mRNA for IL-6 was higher in AMN and EM versus AC (P < 0.01). Expression of IL-8 was higher in AMN than AC and EM (P < 0.001). Steroid receptors and OTR were highly expressed in EM but not in AMN and AC (P < 0.001). Expression of COX2 was most pronounced in AC whereas IL expression was not upregulated in AC. No differences in mRNA expression existed between altrenogest-treated and control animals. Endometrial polymorphonuclear leukocytes were increased in altrenogest-treated mares. Epithelial cells of all tissues, except AC chorionic villi stained progesterone receptor-positive. Staining for ER was more pronounced in the amnion facing epithelium of the AC in altrenogest-treated versus control animals (P < 0.01). In conclusion, COX2 is highly expressed in the AC. The fetal membranes thus might play a role in the onset of labor in the horse. Altrenogest did not affect gene expression in the AMN, AC, and EM but had localized effects on inflammatory cells and ER expression. No anti-inflammatory effects of altrenogest in healthy, late pregnant pony mares could be detected.

  6. Developing anti-inflammatory therapeutics for patients with osteoarthritis.

    PubMed

    Philp, Ashleigh M; Davis, Edward T; Jones, Simon W

    2016-08-07

    OA is the most common joint disorder in the world, but there are no approved therapeutics to prevent disease progression. Historically, OA has been considered a wear-and-tear joint disease, and efforts to identify and develop disease-modifying therapeutics have predominantly focused on direct inhibition of cartilage degeneration. However, there is now increasing evidence that inflammation is a key mediator of OA joint pathology, and also that the link between obesity and OA is not solely due to excessive load-bearing, suggesting therefore that targeting inflammation in OA could be a rewarding therapeutic strategy. In this review we therefore re-evaluate historical clinical trial data on anti-inflammatory therapeutics in OA patients, highlight some of the more promising emerging therapeutic targets and discuss the implications for future clinical trial design.

  7. Anti-inflammatory therapy for obstructive sleep apnea in children

    PubMed Central

    Friedman, Bat-Chen; Goldman, Ran D.

    2011-01-01

    Abstract Question A 4-year-old child was diagnosed by polysomnography as experiencing mild obstructive sleep apnea (OSA). Despite the child being inattentive and distracted during the day at school, his parents prefer to avoid surgical treatment (adenotonsillectomy). Are there any non-surgical treatments for mild OSA in young children? Answer Obstructive sleep apnea in children is caused mainly by adenotonsillar hypertrophy and can lead to considerable morbidities, including neurocognitive and behavioural disturbances. Surgical removal of the tonsils and adenoids is the treatment of choice. In recent years, however, a new understanding of the inflammatory components of OSA has led to the assumption that anti-inflammatory treatment can reduce adenotonsillar size and improve OSA symptoms. Evidence from a few studies suggests that intranasal steroids and oral leukotriene receptor antagonists have beneficial effects, but data from randomized controlled trials are still lacking. PMID:21841108

  8. Antioxidant and Anti-Inflammatory Activities of Barettin

    PubMed Central

    Lind, Karianne F.; Hansen, Espen; Østerud, Bjarne; Eilertsen, Karl-Erik; Bayer, Annette; Engqvist, Magnus; Leszczak, Kinga; Jørgensen, Trond Ø.; Andersen, Jeanette H.

    2013-01-01

    In this paper, we present novel bioactivity for barettin isolated from the marine sponge Geodia barretti. We found that barettin showed strong antioxidant activity in biochemical assays as well as in a lipid peroxidation cell assay. A de-brominated synthetic analogue of barettin did not show the same activity in the antioxidant cell assay, indicating that bromine is important for cellular activity. Barettin was also able to inhibit the secretion of the inflammatory cytokines IL-1β and TNFα from LPS-stimulated THP-1 cells. This combination of anti-inflammatory and antioxidant activities could indicate that barettin has an atheroprotective effect and may therefore be an interesting product to prevent development of atherosclerosis. PMID:23880935

  9. Harnessing the anti-inflammatory potential of palmitoylethanolamide.

    PubMed

    Alhouayek, Mireille; Muccioli, Giulio G

    2014-10-01

    Palmitoylethanolamide (PEA) is a peroxisome proliferator-activated receptor alpha (PPAR-α) ligand that exerts anti-inflammatory, analgesic and neuroprotective actions. PEA is synthetized from phospholipids through the sequential actions of N-acyltransferase and N-acylphosphatidylethanolamine-preferring phospholipase D (NAPE-PLD), and its actions are terminated by its hydrolysis by two enzymes, fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolysing acid amidase (NAAA). Here, we review the impact of PEA administration in inflammatory and neurodegenerative settings and the differential role of FAAH and NAAA in controlling PEA levels. Recent studies with NAAA inhibitors put forth this enzyme as capable of increasing PEA levels in vivo in inflammatory processes, and identified it as an interesting target for drug discovery research. Thus, PEA hydrolysis inhibitors could constitute potential therapeutic alternatives in chronic inflammatory and neurodegenerative diseases.

  10. Anti-inflammatory effects of hydroxycinnamic acid derivatives

    SciTech Connect

    Nagasaka, Reiko; Chotimarkorn, Chatchawan; Shafiqul, Islam Md.; Hori, Masatoshi; Ozaki, Hiroshi; Ushio, Hideki . E-mail: hushio@kaiyodai.ac.jp

    2007-06-29

    NF-{kappa}B family of transcription factors are involved in numerous cellular processes, including differentiation, proliferation, and inflammation. It was reported that hydroxycinnamic acid derivatives (HADs) are inhibitors of NF-{kappa}B activation. Rice bran oil contains a lot of phytosteryl ferulates, one of HADs. We have investigated effects of phytosteryl ferulates on NF-{kappa}B activation in macrophage. Cycloartenyl ferulate (CAF), one of phytosteryl ferulates, significantly reduced lipopolysaccharide (LPS)-induced NO production and mRNA expression of inducible NO synthase and cyclooxygenese-2 but upregulated SOD activity. Electrophoresis mobility shift assay revealed that CAF inhibited DNA-binding of NF-{kappa}B. CAF and phytosteryl ferulates probably have potentially anti-inflammatory properties.

  11. Nonsteroidal Anti-Inflammatory Drugs and the Kidney

    PubMed Central

    Hörl, Walter H.

    2010-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result. PMID:27713354

  12. Pharmacological interactions of anti-inflammatory-analgesics in odontology.

    PubMed

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-02-01

    In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.

  13. [Anti-inflammatory effects of tea-flavonoids].

    PubMed

    Hoensch, H; Oertel, R

    2012-12-01

    Tea flavonoids belong to the large group of polyphenols and display antioxidative, anti-inflammatory and anti-neoplastic activities. These phytochemicals are xenobiotics and are synthesized by tea plants such as Camellia sinensis and Camomilla recucita. These botanicals exhibit in vivo activities similar to that of biologicals which are widely used for chronic inflammatory diseases (rheumatoid arthritis, chronic inflammatory bowel disease). Epigallocathechin gallate and apigenin from these plants inhibit cytokines, chemokines and activated immune cells in vivo and in vitro. Clinical disorders with induced inflammatory pathways could benefit from flavonoid treatment. Dietary supplementation with specific tea-flavonoids could be used for Crohn's disease, ulcerative colitis and irritable bowel syndrome. Suppression of cytokine production could ultimately lead to inhibition of carcinogenesis. This mechanism could explain why flavonoids are effective in the prevention of intestinal neoplasia. This innovative new form of therapy should be tested in controlled, randomized clinical studies.

  14. Go green: the anti-inflammatory effects of biliverdin reductase.

    PubMed

    Wegiel, Barbara; Otterbein, Leo E

    2012-01-01

    Biliverdin (BV) has emerged as a cytoprotective and important anti-inflammatory molecule. Conversion of BV to bilirubin (BR) is catalyzed by biliverdin reductase (BVR) and is required for the downstream signaling and nuclear localization of BVR. Recent data by others and us make clear that BVR is a critical regulator of innate immune responses resulting from acute insult and injury and moreover, that a lack of BVR results in an enhanced proinflammatory phenotype. In macrophages, BVR is regulated by its substrate BV which leads to activation of the PI3K-Akt-IL-10 axis and inhibition of TLR4 expression via direct binding of BVR to the TLR4 promoter. In this review, we will summarize recent findings on the role of BVR and the bile pigments in inflammation in context with its activity as an enzyme, receptor, and transcriptional regulator.

  15. Anti-Inflammatory Activity of Sanghuangporus sanghuang Mycelium

    PubMed Central

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

    2017-01-01

    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. PMID:28178212

  16. Flavone deglycosylation increases their anti-inflammatory activity and absorption

    PubMed Central

    Hostetler, Gregory; Riedl, Ken; Cardenas, Horacio; Diosa-Toro, Mayra; Arango, Daniel; Schwartz, Steven; Doseff, Andrea I.

    2014-01-01

    Scope Flavones have reported anti-inflammatory activities, but the ability of flavone-rich foods to reduce inflammation is unclear. Here, we report the effect of flavone glycosylation in the regulation of inflammatory mediators in vitro and the absorption of dietary flavones in vivo. Methods and results The anti-inflammatory activities of celery extracts, some rich in flavone aglycones and others rich in flavone glycosides, were tested on the inflammatory mediators tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lipopolysaccharide-stimulated macrophages. Pure flavone aglycones and aglycone-rich extracts effectively reduced TNF-α production and inhibited the transcriptional activity of NF-κB, while glycoside-rich extracts showed no significant effects. Deglycosylation of flavones increased cellular uptake and cytoplasmic localization as shown by high-performance liquid chromatography (HPLC) and microscopy using the flavonoid fluorescent dye diphenyl-boric acid 2-aminoethyl ester (DPBA). Celery diets with different glycoside or aglycone contents were formulated and absorption was evaluated in mice fed with 5 or 10% celery diets. Relative absorption in vivo was significantly higher in mice fed with aglycone-rich diets as determined by HPLC-MS/MS (where MS/MS is tandem mass spectrometry). Conclusion These results demonstrate that deglycosylation increases absorption of dietary flavones in vivo and modulates inflammation by reducing TNF-α and NF-κB, suggesting the potential use of functional foods rich in flavones for the treatment and prevention of inflammatory diseases. PMID:22351119

  17. Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages.

    PubMed

    González-Domínguez, Érika; Domínguez-Soto, Ángeles; Nieto, Concha; Flores-Sevilla, José Luis; Pacheco-Blanco, Mariana; Campos-Peña, Victoria; Meraz-Ríos, Marco A; Vega, Miguel A; Corbí, Ángel L; Sánchez-Torres, Carmen

    2016-02-01

    Human CD14(++)CD16(-) and CD14(+/lo)CD16(+) monocyte subsets comprise 85 and 15% of blood monocytes, respectively, and are thought to represent distinct stages in the monocyte differentiation pathway. However, the differentiation fates of both monocyte subsets along the macrophage (Mϕ) lineage have not yet been elucidated. We have now evaluated the potential of CD14(++) CD16(-) and CD16(+) monocytes to differentiate and to be primed toward pro- or anti-inflammatory Mϕs upon culture with GM-CSF or M-CSF, respectively (subsequently referred to as GM14, M14, GM16, or M16). Whereas GM16 and GM14 were phenotypic and functionally analogous, M16 displayed a more proinflammatory profile than did M14. Transcriptomic analyses evidenced that genes associated with M-CSF-driven Mϕ differentiation (including FOLR2, IL10, IGF1, and SERPINB2) are underrepresented in M16 with respect to M14. The preferential proinflammatory skewing of M16 relative to M14 was found to be mediated by the secretion of activin A and the low levels of IL-10 produced by M16. In fact, activin A receptor blockade during the M-CSF-driven differentiation of CD16(+) monocytes, or addition of IL-10-containing M14-conditioned medium, significantly enhanced their expression of anti-inflammatory-associated molecules while impairing their acquisition of proinflammatory-related markers. Thus, we propose that M-CSF drives CD14(++)CD16- monocyte differentiation into bona fide anti-inflammatory Mϕs in a self-autonomous manner, whereas M-CSF-treated CD16(+) monocytes generate Mϕs with a skewed proinflammatory profile by virtue of their high activin A expression unless additional anti-inflammatory stimuli such as IL-10 are provided.

  18. Hypericum in Infection: Identification of Anti-viral and Anti-inflammatory Constituents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum and Prunella supplements for human-health benefit, focusing on anti-viral, anti-inflammatory and anti-pain effects. This paper reports on ongoing anti-viral and anti-inflammatory studies on Hypericu...

  19. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng

    PubMed Central

    Ravikumar, V.R.; Dhanamani, M.; Sudhamani, T.

    2009-01-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium. PMID:22557324

  20. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng.

    PubMed

    Ravikumar, V R; Dhanamani, M; Sudhamani, T

    2009-04-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium.

  1. Issues surrounding the anti-inflammatory actions of the citrus polymethoxylated flavones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The polymethoxylated flavones in citrus have been evaluated for their in vivo anti-inflammatory actions in several animal assays. Strong anti-inflammatory effects were observed following administration of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) dissolved in vegetable oil by intraperitoneal (i.p.) ...

  2. Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...

  3. Enhanced anti-inflammatory activities of Monascus pilosus fermented products by addition of ginger to the medium.

    PubMed

    Chen, Chin-Chu; Chyau, Charng-Cherng; Liao, Chen-Chung; Hu, Tzu-Jung; Kuo, Chia-Feng

    2010-11-24

    Hypercholesterolemia initiates the atherogenic process; however, chronic inflammation promotes atherogenesis. Monascus spp. fermented products are recognized for their anti-hypercholesterolemic effect, but their anti-inflammatory activity is not as significant as that of many plant-derived foods. To enhance the anti-inflammatory function of Monascus pilosus fermented products, ginger was added to the PDB medium at a ratio of 20% (v/v). The mycelia and broth were collected, freeze-dried, and extracted by ethanol for assays. Macrophage RAW264.7 was challenged with lipopolysaccharide (LPS) and coincubated with the extracts of fermented product cultured in ginger-supplemented medium (MPG) or extracts of fermented product cultured in regular PDB medium (MP) for 18 h. Human umbilical vein endothelial cell HUVEC was challenged with tumor necrosis factor (TNF)-α and coincubated with the extracts of either MPG or MP for 6 h. The results showed that MPG significantly (p<0.05) lowered the production of macrophage pro-inflammatory cytokines TNF-α, nitric oxide (NO), interleukin (IL)-1, IL-6, and prostaglandin E2 (PGE2) by 68.53%, 84.29%, 32.55%, 84.49%, and 69.49%, respectively; however, MP had no inhibitory effect. MPG significantly downregulated the expression of p-IκB, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in macrophage by 42.16%, 50.87%, and 51.35%, respectively, while MP had no inhibition on COX-2 expression and only 16.64% and 19.22% downregulatory effect on iNOS and phosphorylated-IκB (p-IκB), respectively. Moreover, MPG significantly suppressed the expression of vessel cell adhesion molecule-1 (VCAM-1) and p-IκB in endothelial cell by 63.48% and 63.41%, respectively. LC/MS/MS analysis indicated that 6-gingerdiol was formed in the ginger-modified medium during fermentation. The results of this study will facilitate the development of Monascus spp. fermented products as antiatherosclerotic nutraceuticals.

  4. Involvement of PKA and HO-1 signaling in anti-inflammatory effects of surfactin in BV-2 microglial cells

    SciTech Connect

    Park, Sun Young; Kim, Ji-Hee; Lee, Sang Joon; Kim, YoungHee

    2013-04-01

    Surfactin, one of the most powerful biosurfactants, is a bacterial cyclic lipopeptide. Here, we investigated the anti-neuroinflammatory properties of surfactin in lipoteichoic acid (LTA)-stimulated BV-2 microglial cells. Surfactin significantly inhibited excessive production of the pro-inflammatory mediators TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), prostaglandin E{sub 2} (PGE{sub 2}), nitric oxide (NO) and reactive oxygen species (ROS), and suppressed the expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent mechanistic studies revealed that surfactin inhibited LTA-induced nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription-1 (STAT-1) activation. However, surfactin increases the phosphorylation of the STAT-3, a component of the homeostatic mechanism causing anti-inflammatory events. We also demonstrated that surfactin induces heme oxygenase-1 (HO-1) expression and nuclear factor-regulated factor-2 (Nrf-2) activation, and that the anti-inflammatory effects of surfactin are abrogated by small interfering RNA-mediated knock-down of HO-1 or Nrf-2. Interestingly, we found that surfactin increased the level of cAMP and induced phosphorylation of cAMP responsive element binding protein (CREB) in microglial cells. Furthermore, treatment with the protein kinase A (PKA) inhibitor, H-89, blocked HO-1 induction by surfactin and abolished surfactin's suppressive effects on ROS and NO production. These results indicate that HO-1 and its upstream effector, PKA, play a pivotal role in the anti-neuroinflammatory response of surfactin in LTA-stimulated microglia. Therefore, surfactin might have therapeutic potential for neuroprotective agents to treat inflammatory and neurodegenerative diseases. - Highlights: ► Surfactin inhibits proinflammatory mediator synthesis in LTA-activated BV-2 cells. ► Surfactin suppresses NF-κB and STAT-1, but potentiates

  5. Anti-Inflammatory Action of Pterostilbene is Mediated Through the p38 Mitogen-Activated Protein Kinase Pathway in Colon Cancer Cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidation and nitration/nitrosation stress and generation of pro-inflammatory cytokines are hallmarks of inflammation. Since chronic inflammation is implicated in several pathological conditions in humans, including cancers of the colon, we have been interested in identifying new anti-inflammatory c...

  6. Anti-inflammatory and antioxidant activity of Ficus carica Linn. leaves.

    PubMed

    Ali, B; Mujeeb, M; Aeri, V; Mir, S R; Faiyazuddin, M; Shakeel, F

    2012-01-01

    Ficus carica Linn. (Moraceae) is commonly known as edible fig. The leaves, roots, fruits and latex of the plant are medicinally used in different diseases. The leaves are claimed to be effective in various inflammatory conditions like painful or swollen piles, insect sting and bites. However, there has been no report on anti-inflammatory and antioxidant activity of F. carica leaves. Therefore the aim of this study was to evaluate the anti-inflammatory and antioxidant activity of F. carica leaves. Our study validated the traditional claim with pharmacological data. Anti-inflammatory and antioxidant activity of the drug could be due to the presence of steroids and flavanoids, respectively, which are reported to be present in the drug. Furthermore, the anti-inflammatory activity of the drug could be due to its free radical scavenging activity. Further work is also required to isolate and characterise the active constituents responsible for the anti-inflammatory activities.

  7. Anti-inflammatory effect of methanol extract from Erigeron Canadensis L. may be involved with upregulation of heme oxygenase-1 expression and suppression of NFκB and MAPKs activation in macrophages

    PubMed Central

    Sung, Jeehye; Sung, Misun; Kim, Younghwa; Ham, Hyeonmi; Jeong, Heon-Sang

    2014-01-01

    BACKGROUND/OBJECTIVES In this study, we determined the anti-inflammatory activities and the underlying molecular mechanisms of the methanol extract from Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells. MATERIALS/METHODS The potential anti-inflammatory properties of ECM were investigated by using RAW264.7 macrophages. We used western blot assays and real time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. RESULTS ECM significantly inhibited inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2) derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory effects of ECM were accompanied by decreases in LPS-induced nuclear translocations and transactivities of NFκB. Moreover, phosphorylation of mitogen-activated protein kinase (MAPKs) including extracellular signal-related kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein expression at the protein levels in dose-dependent manner. However, zinc protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced suppression of NO production. CONCLUSIONS These results suggested that ECM-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects. These findings suggest that ECM exerts anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of Erigeron Canadensis L. PMID:25110553

  8. Comparison of anti-inflammatory activities of an anthocyanin-rich fraction from Portuguese blueberries (Vaccinium corymbosum L.) and 5-aminosalicylic acid in a TNBS-induced colitis rat model

    PubMed Central

    Pereira, Sónia R.; Pereira, Rita; Figueiredo, Isabel; Freitas, Victor; Dinis, Teresa C. P.; Almeida, Leonor M.

    2017-01-01

    Despite the actual therapeutic approaches for inflammatory bowel disease (IBD), efficient and secure alternative options remain a research focus. In this context, anthocyanins seem promising natural anti-inflammatory agents, but their action mechanisms and efficacy as compared with established drugs still require more clarification. The main aim of this study was to compare the anti-inflammatory action of a chemically characterized anthocyanin-rich fraction (ARF), obtained from Portuguese blueberries (Vaccinium corymbosum L.), with that of 5-aminosalicylic acid (5-ASA), a first-line drug in IBD, in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model. Such fraction showed a high content and great molecular diversity of anthocyanins, with malvidin-3-galactoside and petunidin-3-arabinoside in the highest concentrations. After daily administration by intragastric infusion for 8 days, ARF, at a molar anthocyanin concentration about 30 times lower than 5-ASA, showed a higher effectiveness in counteracting the intestinal inflammation, as assessed by i) body weight variation and colon damage score, ii) reduction in leukocyte infiltration, iii) increase in antioxidant defenses and iv) by downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon tissue homogenates. The strong inhibition of COX-2 expression seems to be a crucial anti-inflammatory mechanism common to both ARF and 5-ASA, but the additional higher abilities of anthocyanins to downregulate iNOS and to decrease leukocytes infiltration and to increase antioxidant defenses in colon may account for the much higher anti-inflammatory action of anthocyanins. These data may contribute to the development of a promising natural approach in IBD management. PMID:28329021

  9. Oolong tea theasinensins attenuate cyclooxygenase-2 expression in lipopolysaccharide (LPS)-activated mouse macrophages: structure-activity relationship and molecular mechanisms.

    PubMed

    Hou, De-Xing; Masuzaki, Satoko; Tanigawa, Shunsuke; Hashimoto, Fumio; Chen, Jihua; Sogo, Takayuki; Fujii, Makoto

    2010-12-22

    Oolong tea theasinensins are a group of tea polyphenols different from green tea catechins and black tea theaflavins. The present study reports the inhibitory effects of oolong tea theasinensins on the expression of cyclooxygenase-2 (COX-2) and underlying molecular mechanisms in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. The structure-activity data revealed that the galloyl moiety of theasinensins played an important role in the inhibitory actions. Theasinensin A, a more potent inhibitor, caused a dose-dependent inhibition of mRNA, protein, and promoter activity of COX-2. An electrophoretic mobility shift assay (EMSA) revealed that theasinensin A reduced the complex of NF-κB- and AP-1-DNA in the promoter of COX-2. Signaling analysis demonstrated that theasinensin A attenuated IκB-α degradation, nuclear p65 accumulation, and c-Jun phosphorylation. Furthermore, theasinensin A suppressed the phosphorylation of MAPKs, IκB kinase α/β (IKKα/β), and TGF-β activated kinase (TAK1). These data demonstrated that the down-regulation of TAK1-mediated MAPKs and NF-κB signaling pathways might be involved in the inhibition of COX-2 expression by theasinensin A. These findings provide the first molecular basis for the anti-inflammatory properties of oolong tea theasinensins.

  10. Cyclooxygenase-2 or tumor necrosis factor-α inhibitors attenuate the mechanotransductive effects of pulsed focused ultrasound to suppress mesenchymal stromal cell homing to healthy and dystrophic muscle.

    PubMed

    Tebebi, Pamela A; Burks, Scott R; Kim, Saejeong J; Williams, Rashida A; Nguyen, Ben A; Venkatesh, Priyanka; Frenkel, Victor; Frank, Joseph A

    2015-04-01

    Maximal homing of infused stem cells to diseased tissue is critical for regenerative medicine. Pulsed focused ultrasound (pFUS) is a clinically relevant platform to direct stem cell migration. Through mechanotransduction, pFUS establishes local gradients of cytokines, chemokines, trophic factors (CCTF) and cell adhesion molecules (CAM) in treated skeletal muscle that subsequently infused mesenchymal stromal cells (MSC) can capitalize to migrate into the parenchyma. Characterizing molecular responses to mechanical pFUS effects revealed tumor necrosis factor-alpha (TNFα) drives cyclooxygenase-2 (COX2) signaling to locally increase CCTF/CAM that are necessary for MSC homing. pFUS failed to increase chemoattractants and induce MSC homing to treated muscle in mice pretreated with ibuprofen (nonspecific COX inhibitor) or etanercept (TNFα inhibitor). pFUS-induced MSC homing was also suppressed in COX2-knockout mice, demonstrating ibuprofen blocked the mechanically induced CCTF/CAM by acting on COX2. Anti-inflammatory drugs, including ibuprofen, are administered to muscular dystrophy (MD) patients, and ibuprofen also suppressed pFUS-induced homing to muscle in a mouse model of MD. Drug interactions with cell therapies remain unexplored and are not controlled for during clinical cell therapy trials. This study highlights potentially negative drug-host interactions that suppress stem cell homing and could undermine cell-based approaches for regenerative medicine.

  11. Anti-inflammatory effect of resveratrol in old mice liver.

    PubMed

    Tung, Bui Thanh; Rodríguez-Bies, Elisabeth; Talero, Elena; Gamero-Estévez, Enrique; Motilva, Virginia; Navas, Plácido; López-Lluch, Guillermo

    2015-04-01

    Inflammation is a hallmark of aging. Caloric restriction and resveratrol (RSV) have shown important effects on prevention of oxidative stress and inflammation. Here, we investigate the progression of proinflammatory markers in liver during aging and the effect of RSV on inflammation markers in the liver of old male C57BL/6J mice. Young (2 months), mature (12 months) and old (18 months) mice were fed during 6 months with RSV. Levels of IL-1β, IL-6, IL-10, IL-17 and TNF-α were evaluated by ELISA in mice liver. Levels of pro-inflammatory cytokines, IL-1β, IL-6, IL-17 and TNF-α and also their respective mRNA increased in the liver from old mice. However, RSV decreased these levels in the case of IL-1β and TNF-α but only in old mice showing no effect on young and mature animals. This reduction was also found at the mRNA level. Levels of mRNA of the components of NALP-3 inflammasome, ASC, CASP-1, NALP-1 and NALP-3, also showed an age-dependent increase that was reversed by RSV. Furthermore, cyclooxygenase 2 levels, a marker of proinflammatory innate immune activity, were also upregulated in aged liver and reversed again by RSV. In conclusion, our study confirms that aging is accompanied by an increase in the proinflammatory pattern in the liver and that RSV reduces this pattern in old mice liver.

  12. Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non-steroidal anti-inflammatory drug nabumetone.

    PubMed

    Roy, H K; Karolski, W J; Ratashak, A

    2001-05-15

    Use of non-steroidal anti-inflammatory drugs (NSAIDs) for chemoprevention of colon cancer has been hindered by their potential gastro-intestinal toxicity. Nabumetone, which is approximately 10 to 36 times safer than conventional NSAIDs, was evaluated in 2 models of experimental colon carcinogenesis. In azoxymethane (AOM)-treated Fisher 344 rats, nabumetone caused dose-dependent inhibition of aberrant crypt foci (ACF), with 750 and 1,500 ppm resulting in 15% and 37% reductions, respectively (p < 0.05). Moreover, complex ACF were reduced by 48% in the latter group. MIN mice studies confirmed the chemopreventive efficacy of nabumetone, with 900 ppm suppressing approximately half of the intestinal tumors. Interestingly, inhibition of intermediate biomarkers in both models was markedly greater in the distal than the proximal bowel. To mechanistically evaluate this regional selectivity, we assessed cyclo-oxygenase-2 (COX-2) expression in the uninvolved mucosa and demonstrated a 3- to 4-fold excess in the distal relative to the proximal bowel in both MIN mice and AOM-treated rats. We then investigated another putative NSAID target, peroxisome proliferator-activated receptor-delta (PPAR-delta) and demonstrated up-regulation during AOM-induced colonic tumorigenesis. Furthermore, in pre-neoplastic mucosa, there was a 3-fold excess of PPAR-delta in the distal colon. We demonstrate that nabumetone is an effective protective agent in both experimental models of colon carcinogenesis. The striking distal predilection of nabumetone may be, at least partially, explained by distal bowel over-expression of COX-2 and PPAR-delta.

  13. The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury.

    PubMed

    Thau-Zuchman, Orli; Shohami, Esther; Alexandrovich, Alexander G; Trembovler, Victoria; Leker, Ronen R

    2012-01-20

    Traumatic brain injury (TBI) initiates acute and chronic inflammatory processes involving cyclooxygenase-2 (COX-2), which may have detrimental effects on outcome and especially on brain regeneration. Therefore we aimed to study whether carprofen, a COX-2 inhibitor, would improve outcome and increase neurogenesis after TBI. TBI was induced in Sabra mice that were then treated with vehicle or carprofen for 7 days. Functional outcome was evaluated with the Neurological Severity Score (NSS).Cytokine levels were assessed 4 h post-TBI and water content was measured 24 h post TBI. Mice were given BrdU to label newborn cells for 10 days. The animals were killed 90 days post-TBI and the lesion size as well as newborn cell fate were assessed. Carprofen significantly reduced lesion size (p=0.002), decreased water content in the lesioned cortex (p=0.03), reduced the number of microglia in the lesioned cortex (p<0.0001), and lowered the levels of proinflammatory cytokines (IL-1β, p=0.03; IL-6, p=0.02). Carprofen led to significantly larger improvements in functional outcome (p≤0.008) which were durable over 90 days. Carprofen also induced a threefold increase in the proliferation of new cells in the peri-lesion area (p≤0.002), but newborn cells differentiated mainly into glia in both groups. Carprofen is neuroprotective and induces cell proliferation and gliogenesis after TBI. Treatment with carprofen is consistently associated with better functional outcome. Our results imply that anti-inflammatory drugs may represent novel therapeutic options for TBI.

  14. Membranous nephropathy and nonsteroidal anti-inflammatory agents.

    PubMed

    Nawaz, Fareha A; Larsen, Christopher P; Troxell, Megan L

    2013-11-01

    Membranous nephropathy presents clinically as nephrotic syndrome, with subepithelial immune complex deposits seen on biopsy. Historically, in about three-quarters of membranous cases, no obvious etiologic agent or condition can be identified. More recently, serum antibodies to the phospholipase A2 receptor have been discovered in many patients with primary/idiopathic membranous nephropathy. About one-quarter of patients have membranous nephropathy as a manifestation of another systemic disorder, such as autoimmune conditions, infection, malignancy, toxin exposure, or drugs (classically gold or penicillamine). In this report, we present a case of recurrent nephrotic syndrome with biopsy-proven membranous nephropathy closely associated with use of the nonsteroidal anti-inflammatory drugs (NSAIDs) naproxen and piroxicam. Characterization of the immunoglobulin G (IgG) subclass profile of the deposits showed abundant IgG1, weak IgG4, and positive staining for phospholipase A2 receptor. This case serves to highlight membranous nephropathy as an under-recognized renal complication of NSAID use. Other kidney effects of NSAIDs, such as hemodynamic compromise, interstitial nephritis, and minimal change disease, are more broadly recognized.

  15. Chondroprotective and anti-inflammatory effects of sesamin.

    PubMed

    Phitak, Thanyaluck; Pothacharoen, Peraphan; Settakorn, Jongkolnee; Poompimol, Wilart; Caterson, Bruce; Kongtawelert, Prachya

    2012-08-01

    Osteoarthritis (OA) is a major disability of elderly people. Sesamin is the main compound in Sesamun indicum Linn., and it has an anti-inflammatory effect by specifically inhibiting Δ5-desaturase in polyunsaturated fatty acid biosynthesis. The chondroprotective effects of sesamin were thus studied in a porcine cartilage explant induced with interleukin-1beta (IL-1β) and in a papain-induced osteoarthritis rat model. With the porcine cartilage explant, IL-1β induced release of sulfated-glycosaminoglycan (s-GAG) and hydroxyproline release, and this induction was significantly inhibited by sesamin. This ability to inhibit these processes might be due to its ability to decrease expression of MMP-1, -3 and -13, which can degrade both PGs and type II collagen, both at the mRNA and protein levels. Interestingly, activation of MMP-3 might also be inhibited by sesamin. Moreover, in human articular chondrocytes (HACs), some pathways of IL-1β signal transduction were inhibited by sesamin: p38 and JNK. In the papain-induced OA rat model, sesamin treatment reversed the following pathological changes in OA cartilage: reduced disorganization of chondrocytes in cartilage, increased cartilage thickness, and decreased type II collagen and PGs loss. Sesamin alone might increase formation of type II collagen and PGs in the cartilage tissue of control rats. These results demonstrate that sesamin efficiently suppressed the pathological processes in an OA model. Thus, sesamin could be a potential therapeutic strategy for treatment of OA.

  16. Anti-inflammatory properties of drugs from saffron crocus.

    PubMed

    Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe

    2012-01-01

    The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity.

  17. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; OʼDaly, Owen; Thacker, Michael A; Zelaya, Fernando O; Wooldridge, Caroline L; Renton, Tara F; Williams, Steven C R; Howard, Matthew A

    2015-07-01

    Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.

  18. Anti-Inflammatory Components from the Root of Solanum erianthum

    PubMed Central

    Chen, Yu-Chang; Lee, Hong-Zin; Chen, Hsin-Chun; Wen, Chi-Luan; Kuo, Yueh-Hsiung; Wang, Guei-Jane

    2013-01-01

    Two new norsesquiterpenoids, solanerianones A and B (1–2), together with nine known compounds, including four sesquiterpenoids, (−)-solavetivone (3), (+)-anhydro-β-rotunol (4), solafuranone (5), lycifuranone A (6); one alkaloid, N-trans-feruloyltyramine (7); one fatty acid, palmitic acid (8); one phenylalkanoid, acetovanillone (9), and two steroids, β-sitosterol (10) and stigmasterol (11) were isolated from the n-hexane-soluble part of the roots of Solanum erianthum. Their structures were elucidated on the basis of physical and spectroscopic data analyses. The anti-inflammatory activity of these isolates was monitored by nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells. The cytotoxicity towards human lung squamous carcinoma (CH27), human hepatocellular carcinoma (Hep 3B), human oral squamous carcinoma (HSC-3) and human melanoma (M21) cell lines was also screened by using an MTT assay. Of the compounds tested, 3 exhibited the strongest NO inhibition with the average maximum inhibition (Emax) at 100 μM and median inhibitory concentration (IC50) values of 98.23% ± 0.08% and 65.54 ± 0.18 μM, respectively. None of compounds (1–9) was found to possess cytotoxic activity against human cancer cell lines at concentrations up to 30 μM. PMID:23771024

  19. Nanocarriers for Vascular Delivery of Anti-Inflammatory Agents

    PubMed Central

    Howard, Melissa D.; Hood, Elizabeth D.; Zern, Blaine; Shuvaev, Vladimir V.; Grosser, Tilo; Muzykantov, Vladimir R.

    2017-01-01

    There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation. PMID:24392694

  20. Topical nonsteroidal anti-inflammatory drugs for osteoarthritis.

    PubMed

    Barthel, H Richard; Axford-Gatley, Robert A

    2010-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of the treatment of osteoarthritis (OA) but have dose- and age-related risks of gastrointestinal, cardiovascular, and renal adverse events (AEs). As a result, US and international guidelines recommend caution when prescribing oral NSAIDs, particularly in older patients and those with significant comorbidities. For OA of the hands and knees, topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic distribution. Treatment-related cardiovascular, renal, and other serious AEs with topical NSAIDs have not been reported. At present, only 2 topical NSAIDs are approved in the United States for the treatment of OA: diclofenac sodium 1% gel for hand or knee OA and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution for knee OA. Clinical trial data for these products have demonstrated efficacy superior to placebo or similar to oral diclofenac with AE profiles similar to placebo, except for application site reactions. In large double-blind trials, gastrointestinal AEs were infrequent and did not include ulcers, perforations, or bleeding. The purpose of this brief review is to examine the data from controlled double-blind trials evaluating the use of topical NSAIDs in patients with OA. Articles included were identified via a search of PubMed covering the period from January 1, 2005 through March 31, 2010. Reference lists from OA treatment guidelines and meta-analyses were reviewed for additional citations of importance.

  1. Anti-inflammatory lanostanoids and lactone derivatives from Antrodia camphorata.

    PubMed

    Liaw, Chih-Chuang; Chen, Yu-Chang; Huang, Guan-Jhong; Tsai, Yao-Ching; Chien, Shih-Chang; Wu, Jyh-Horng; Wang, Sheng-Yang; Chao, Louis Kuoping; Sung, Ping-Jyun; Huang, Hui-Chi; Kuo, Yueh-Hsiung

    2013-04-26

    Four new lanostanoids, ethyl lucidenate A (1), ethyl lucidenate F (2), 15-O-acetylganolucidate A (3), and 3,11,15,23-tetraoxo-27ξ-lanosta-8,16-dien-26-oic acid (4), and two new lactone derivatives, 5-hydroxy-5-(methoxymethyl)-4-methylfuran-2(5H)-one (5) and 3-(4-methoxy-2-oxo-2H-pyran-6-yl)propanoic acid (6), together with four known compounds, 11α-hydroxy-3,7-dioxolanost-8,24(E)-dien-26- oic acid (7), 3,7,11-trioxo-5α-lanosta-8,24(E)-dien-26-oic acid (8), methyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate (9), and ethyl 3,7,11,12,15,23-hexaoxo-5α-lanost-8-en-26-oate (10), were characterized from Antrodia camphorata. The structures of these new compounds were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments. Ten components were evaluated for anti-inflammatory activity by examining their effect on LPS-iNOS-dependent NO production in murine macrophage (RAW 264.7) cells. Among them, compounds 1, 3, 7, 8, 9, and 10 significantly suppressed the NO concentration in LPS-treated RAW 264.7 cells with IC50 values ≤ 10 μM.

  2. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    PubMed Central

    Roth, Sanford H

    2011-01-01

    Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis. PMID:21753867

  3. Non-steroidal Anti-inflammatory Drugs in Raptors

    USGS Publications Warehouse

    Oaks, J. Lindsay; Meteyer, Carol U.; Miller, R. Eric; Fowler, Murray E.

    2012-01-01

    The use of analgesia has become standard, and appropriate, practice in avian medicine. As in mammals, pain control in avian patients is usually accomplished with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) used singly or in combination for a multimodal approach. Despite their usefulness, widespread use, and relative safety in clinical use, few controlled studies in birds have been conducted on efficacy, safety, and dosing. The guidelines for the use of NSAIDs in raptors and other birds have mainly been empirical. More recently, NSAIDs in free-living raptors have emerged as a major conservation issue with the discovery that diclofenac sodium was responsible for the population crash of three species of Gyps vultures in southern Asia. In this context, residues of veterinary NSAIDs in domestic animals are now considered environmental contaminants that can be significantly toxic to vultures and possibly other avian scavengers. Ironically, the disaster with Asian vultures has led to a considerable body of research on NSAIDs in raptors to the benefit of clinicians who now have scientific information available to help assess dosing, safety, toxicity, and pharmacokinetics of NSAIDs in their raptor patients.

  4. Invited review: The anti-inflammatory properties of dairy lipids.

    PubMed

    Lordan, R; Zabetakis, I

    2017-03-22

    Dairy product consumption is often associated with negative effects because of its naturally high levels of saturated fatty acids. However, recent research has shown that dairy lipids possess putative bioactivity against chronic inflammation. Inflammation triggers the onset of several chronic diseases, including cardiovascular disease, type 2 diabetes mellitus, obesity, and cancer. This review discusses the anti-inflammatory properties of dairy lipids found in milk, yogurt, and cheese, and it examines them in relation to their implications for human health: their protective effects and their role in pathology. We also consider the effect of lipid profile alteration in dairy products-by using ruminant dietary strategies to enrich the milk, or by lipid fortification in the products. We critically review the in vivo, in vitro, ex vivo, and epidemiological studies associated with these dairy lipids and their role in various inflammatory conditions. Finally, we discuss some suggestions for future research in the study of bioactive lipids and dairy products, with reference to the novel field of metabolomics and epidemiological studies.

  5. Preventing peridural fibrosis with nonsteroidal anti-inflammatory drugs

    PubMed Central

    Hernandez-Vaquero, Daniel

    2008-01-01

    Peridural fibrosis is one of the more frequent complications of lumbar surgery. Nonsteroidal anti-inflammatory drugs inhibit the inflammatory and fibroblastic response. We performed lumbar laminectomies in 24 rabbits, divided into two groups. The experimental group received 5 mg/kg/day of aceclofenac for 7 days and the control group received 1 cm3 of physiological saline. The samples were stained using immunohistochemical methods. The cellular populations in the inflammatory reaction and the thickness of the fibrous membrane were quantified. The mean of the fibrous area was always less in the rabbits of the experimental group compared to controls (47% less at 2 weeks and 41% less at 4 weeks). We observed an 8% decrease in the number of fibroblasts with antivimentin monoclonal antibodies in the experimental group. In this model, aceclofenac inhibits the presence of inflammatory cells in the fibrous scar in the early stages and reduces the extension of adhesions without adverse reactions. PMID:18172695

  6. Incorporation of anti-inflammatory agent into mesoporous silica

    NASA Astrophysics Data System (ADS)

    Rodrigues Braz, Wilson; Lamec Rocha, Natállia; de Faria, Emerson H.; Silva, Márcio L. A. e.; Ciuffi, Katia J.; Tavares, Denise C.; Furtado, Ricardo Andrade; Rocha, Lucas A.; Nassar, Eduardo J.

    2016-09-01

    The unique properties of macroporous, mesoporous, and microporous systems, including their ability to accommodate molecules of different sizes inside their pores and to act as drug delivery systems, have been the object of extensive studies. In this work, mesoporous silica with hexagonal structure was obtained by template synthesis via the sol-gel process. The resulting material was used as support to accommodate the anti-inflammatory agent indomethacin. The alkaline route was used to prepare the mesoporous silica; cetyltrimethylammonium bromide was employed as porogenic agent. The silica particles were functionalized with 3-aminopropyltriethoxysilane alkoxide (APTES) by the sol-gel post-synthesis method. Indomethacin was incorporated into the silica functionalized with APTES and into non-functionalized silica. The resulting systems were characterized by x-ray diffraction (XRD), specific area, infrared spectroscopy, and thermal analyses (TGA). XRD attested to formation of mesoporous silica with hexagonal structure. This structure remained after silica functionalization with APTES and incorporation of indomethacin. Typical infrared spectroscopy vibrations and organic material decomposition during TGA confirmed silica functionalization and drug incorporation. The specific surface area and pore volume of the functionalized material incorporated with indomethacin decreased as compared with the specific surface area and pore volume of the non-functionalized silica containing no drug, suggesting both the functionalizing agent and the drug were present in the silica. Cytotoxicity tests conducted on normal fibroblasts (GM0479A) cells attested that the silica matrix containing indomethacin was less toxic than the free drug.

  7. Incorporation of anti-inflammatory agent into mesoporous silica.

    PubMed

    Braz, Wilson Rodrigues; Rocha, Natállia Lamec; de Faria, Emerson H; Silva, Márcio L A E; Ciuffi, Katia J; Tavares, Denise C; Furtado, Ricardo Andrade; Rocha, Lucas A; Nassar, Eduardo J

    2016-09-23

    The unique properties of macroporous, mesoporous, and microporous systems, including their ability to accommodate molecules of different sizes inside their pores and to act as drug delivery systems, have been the object of extensive studies. In this work, mesoporous silica with hexagonal structure was obtained by template synthesis via the sol-gel process. The resulting material was used as support to accommodate the anti-inflammatory agent indomethacin. The alkaline route was used to prepare the mesoporous silica; cetyltrimethylammonium bromide was employed as porogenic agent. The silica particles were functionalized with 3-aminopropyltriethoxysilane alkoxide (APTES) by the sol-gel post-synthesis method. Indomethacin was incorporated into the silica functionalized with APTES and into non-functionalized silica. The resulting systems were characterized by x-ray diffraction (XRD), specific area, infrared spectroscopy, and thermal analyses (TGA). XRD attested to formation of mesoporous silica with hexagonal structure. This structure remained after silica functionalization with APTES and incorporation of indomethacin. Typical infrared spectroscopy vibrations and organic material decomposition during TGA confirmed silica functionalization and drug incorporation. The specific surface area and pore volume of the functionalized material incorporated with indomethacin decreased as compared with the specific surface area and pore volume of the non-functionalized silica containing no drug, suggesting both the functionalizing agent and the drug were present in the silica. Cytotoxicity tests conducted on normal fibroblasts (GM0479A) cells attested that the silica matrix containing indomethacin was less toxic than the free drug.

  8. Anti-inflammatory effects of macrolides: applications in chronic rhinosinusitis.

    PubMed

    Harvey, Richard J; Wallwork, Ben D; Lund, Valerie J

    2009-11-01

    The anti-inflammatory effects of macrolides are significant. The clinical impact on diffuse panbronchiolitis (DPB) has improved 10-year survival from 12% to more than 90% for these patients. The immunomodulatory activity of macrolides has been a source of mechanistic research as well as clinical research in non-DPB inflammatory airway disease. Suppression of neutrophilic inflammation of the airways has been demonstrated as the most robust immunomodulatory response from 14- and 15-membered ring macrolides. The inhibition of transcription factors, mainly nuclear factor-kB and activator protein 1, from alterations in intracellular cell signaling drives this mechanism. The suppression of interleukin-8 to a range of endogenous and exogenous challenges characterizes the alterations to cytokine production. The inflammatory mechanisms of chronic rhinosinusitis (CRS) have been a major non-DPB focus. Macrolides have been trialed in more than 14 prospective trials and are the focus of numerous research projects. Evidence for a strong clinical effect in CRS is mounting, but results may be tempered by researchers' inability to characterize the disease process. Eosinophilic dominated CRS is unlikely to respond, based on current research understanding and data from clinical trials. This article discusses the current concepts of macrolides and their application in the management of CRS.

  9. Convergence of Nitric Oxide and Lipid Signaling: Anti-Inflammatory Nitro-Fatty Acids

    PubMed Central

    Baker, Paul R.S.; Schopfer, Francisco J.; O’Donnell, Valerie B.; Freeman, Bruce A.

    2009-01-01

    The signaling mediators nitric oxide (·NO) and oxidized lipids, once viewed to transduce metabolic and inflammatory information via discrete and independent pathways, are now appreciated as interdependent regulators of immune response and metabolic homeostasis. The interactions between these two classes of mediators result in reciprocal control of mediator sythesis that is strongly influenced by the local chemical environment. The relationship between the two pathways extends beyond co-regulation of ·NO and eicosanoid formation to converge via the nitration of unsaturated fatty acids to yield nitro derivatives (NO2-FA). These pluripotent signaling molecules are generated in vivo as an adaptive response to oxidative inflammatory conditions and manifest predominantly anti-inflammatory signaling reactions. These actions of NO2-FA are diverse, with these species serving as a potential chemical reserve of ·NO, reacting with cellular nucleophiles to post-translationally modify protein structure, function and localization. In this regard these species act as potent endogenous ligands for peroxisome proliferator activated receptor γ. Functional consequences of these signaling mechanisms have been shown in multiple model systems, including the inhibition of platelet and neutrophil functions, induction of heme oxygenase-1, inhibition of LPS-induced cytokine release in monocytes, increased insulin sensitivity and glucose uptake in adipocytes and relaxation of pre-constricted rat aortic segments. These observations have propelled further in vitro and in vivo studies of mechanisms of NO2-FA signaling and metabolism, highlighting the therapeutic potential of this class of molecules as anti-inflammatory drug candidates. PMID:19200454

  10. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus.

    PubMed

    Serhan, C N; Chiang, N

    2008-03-01

    Complete resolution of an acute inflammatory response and its return to homeostasis are essential for healthy tissues. Here, we overview ongoing efforts to characterize cellular and molecular mechanisms that govern the resolution of self-limited inflammation. Systematic temporal analyses of evolving inflammatory exudates using mediator lipidomics-informatics, proteomics, and cellular trafficking with murine resolving exudates demonstrate novel endogenous pathways of local-acting mediators that share both anti-inflammatory and pro-resolving properties. In murine systems, resolving-exudate leukocytes switch their phenotype to actively generate new families of mediators from major omega-3 fatty acids EPA and DHA termed resolvins and protectins. Recent advances on their biosynthesis and actions are reviewed with a focus on the E-series resolvins (RvE1, RvE2), D series resolvins (RvD1, RvD2) and the protectins including neuroprotectin D1/protectin D1 (NPD1/PD1) as well as their aspirin-triggered epimeric forms. Members of each new family demonstrate potent stereo-specific actions, joining the lipoxins as endogenous local signals that govern resolution and endogenous anti-inflammation mechanisms. In addition to their origins and roles in resolution biology in the immune system, recent findings indicate that these new mediator families also display potent protective actions in lung, kidney, and eye as well as enhance microbial clearance. Thus, these endogenous agonists of resolution pathways constitute a novel genus of chemical mediators that possess pro-resolving, anti-inflammatory, and antifibrotic as well as host-directed antimicrobial actions. These may be useful in the design of new therapeutics and treatments for diseases with the underlying trait of uncontrolled inflammation and redox organ stress.

  11. Anti-inflammatory and anti-itch activity of sertaconazole nitrate.

    PubMed

    Liebel, Frank; Lyte, Peter; Garay, Michelle; Babad, Jeffrey; Southall, Michael D

    2006-09-01

    Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight anti-fungal agents (butoconazole, ciclopirox olamine, fluconazole, miconazole nitrate, sertaconazole nitrate, terconazole, tioconazole and ketoconazole) were compared in a number of preclinical models of dermal inflammation and pruritus. While butoconazole, ciclopirox olamine, fluconazole, and miconazole nitrate were all found to have anti-inflammatory activity, only sertaconazole nitrate reduced the release of cytokines from activated lymphocytes and mitigated inflammation in animal models of irritant contact dermatitis and neurogenic inflammation. In addition, sertaconazole nitrate inhibited contact hypersensitivity and scratching responses in a murine model of pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of sertaconazole nitrate was found to be greater than other topical anti-fungal agents examined. These studies demonstrate that topical administration of clinically relevant concentrations of sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal inflammation models and itch. The anti-inflammatory properties of sertaconazole may contribute to the efficacy of the drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other anti-fungal agents.

  12. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012

    PubMed Central

    Schmidt, Morten; Hallas, Jesper; Friis, Søren

    2014-01-01

    Background Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID) use can be obtained from prescription registries. Objectives To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012 and to quantify the proportion of total sales that was sold on prescription. Method Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription. Results Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year prevalence of prescribed low-dose aspirin increased throughout the study period, notably among men. Nonaspirin NSAID use was frequent in all age groups above 15 years and showed a female preponderance. Overall, the prevalence of prescribed nonaspirin NSAIDs decreased moderately after 2004, but substantial variation according to NSAID subtype was observed; ibuprofen use increased, use of all newer selective cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by nearly 50% after 2008, and naproxen use remained stable. As of 2012, the prescribed proportion of individual-level NSAID sales was 92% for low-dose aspirin, 66% for ibuprofen, and 100% for all other NSAIDs. Conclusion The potential for identifying NSAID use from prescription registries in Denmark is high. Low-dose aspirin and nonaspirin NSAID use varied substantially between 1999 and 2012. Notably, use of cyclooxygenase-2 inhibitors nearly ceased, use of diclofenac decreased markedly, and naproxen use remained unaltered. PMID:24872722

  13. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities.

    PubMed

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-09-16

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested.

  14. The Promise and Limitations of Anti-Inflammatory Agents for the Treatment of Major Depressive Disorder.

    PubMed

    Raison, Charles L

    2017-01-01

    This review provides a critical perspective on recent meta-analyses suggesting that several anti-inflammatory modalities, including nonsteroidal anti-inflammatory drugs (NSAIDs), omega-3 fatty acids, and cytokine antagonist, possess generalizable antidepressant properties. By examining confounds and limitations in the available literature it is suggested that current data suggest that only a sub-group of individuals with major depressive disorder (MDD) have evidence of increased inflammatory biomarkers and it is in these individuals that anti-inflammatory agents show promise for reducing depressive symptoms. The treatment implications of this cautionary perspective are discussed.

  15. Synthesis and biological evaluation of new quinoxaline derivatives as antioxidant and anti-inflammatory agents.

    PubMed

    Burguete, Asunción; Pontiki, Eleni; Hadjipavlou-Litina, Dimitra; Ancizu, Saioa; Villar, Raquel; Solano, Beatriz; Moreno, Elsa; Torres, Enrique; Pérez, Silvia; Aldana, Ignacio; Monge, Antonio

    2011-04-01

    We report the synthesis, anti-inflammatory, and antioxidant activities of novel quinoxaline and quinoxaline 1,4-di-N-oxide derivatives. Microwave-assisted methods have been used to optimize reaction times and to improve yields. The tested compounds presented important scavenging activities and promising in vitro inhibition of soybean lipoxygenase (LOX). Two of the best LOX inhibitors (compounds 7b and 8f) were evaluated as in vivo anti-inflammatory agents using the carrageenin-induced edema model. One of them (compound 7b) showed important in vivo anti-inflammatory effect (41%) similar to that of indomethacin (47%) used as the reference drug.

  16. Impact of Anti-Inflammatory Drugs on Pyogenic Vertebral Osteomyelitis: A Prospective Cohort Study

    PubMed Central

    Jean, Maxime; Bouchand, Frédérique; Davido, Benjamin; Descatha, Alexis; Duran, Clara; Gras, Guillaume; Perronne, Christian; Mulleman, Denis; Salomon, Jérôme; Bernard, Louis

    2016-01-01

    Objective. Pyogenic vertebral osteomyelitis (PVO) are frequently misdiagnosed and patients often receive anti-inflammatory drugs for their back pain. We studied the impact of these medications. Methods. We performed a prospective study enrolling patients with PVO and categorized them depending on their drugs intake. Then, we compared diagnosis delay, clinical presentation at hospitalization, incidence of complications, and cure rate. Results. In total, 79 patients were included. Multivariate analysis found no correlation between anti-inflammatory drug intake and diagnosis delay, clinical presentation, complications, or outcome. Conclusion. Anti-inflammatory drugs intake does not affect diagnostic delay, severity at diagnosis, or complications of PVO. PMID:27833642

  17. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities

    PubMed Central

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-01-01

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested. PMID:26389925

  18. Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from Arthrospira platensis: contribution to bioactivities by the non-phycocyanin aqueous fraction.

    PubMed

    Jensen, Gitte S; Attridge, Victoria L; Beaman, Joni L; Guthrie, Jesse; Ehmann, Axel; Benson, Kathleen F

    2015-05-01

    The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin-Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both the PC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant (p<.05) at doses between 125-500 μg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.

  19. Oral administration of Lactobacillus plantarum K68 ameliorates DSS-induced ulcerative colitis in BALB/c mice via the anti-inflammatory and immunomodulatory activities.

    PubMed

    Liu, Yen-Wenn; Su, Yu-Wen; Ong, Wei-Kee; Cheng, Tzu-Hao; Tsai, Ying-Chieh

    2011-12-01

    Many different kinds of fermented food are consumed daily in Taiwan, such as stinky tofu, suan-tsai, and fu-tsai. We have previously reported the diversity of lactic acid bacteria (LAB) at different stages of fermentation in the production of suan-tsai and fu-tsai. In this study, the anti-inflammatory and immunomodulatory activities of Lactobacillus plantarum K68 (K68) isolated from fu-tsai were evaluated. K68 significantly inhibited the production of tumor necrosis factor-α (TNF-α) and prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells and stimulated interferon-γ (IFN-γ) production in human peripheral blood mononuclear cells (hPBMCs). Additionally, orally administered K68 ameliorated dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in BALB/c mice. Both the disease activity index (DAI) and histological scores (HIS) showed that the severity of UC was significantly reduced by oral administration of K68. Furthermore, the production of pro inflammatory cytokines TNF-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) was significantly reduced in K68-administered group. Colonic mRNA expression levels of TNF-α, cyclooxygenase-2 (COX-2), forkhead box P3 (Foxp3), suppressors of cytokine signaling 3 (SOCS3), and toll like receptor 4 (TLR4), were also reduced in the K68-administered group. These results suggest that K68 exhibits anti-inflammatory and immunomodulatory activities that ameliorate DSS-induced experimental colitis.

  20. Anti-inflammatory effect of enzymatic hydrolysates from Styela clava flesh tissue in lipopolysaccharide-stimulated RAW 264.7 macrophages and in vivo zebrafish model

    PubMed Central

    Ko, Seok-Chun

    2015-01-01

    BACKGROUND/OBJECTIVES In this study, potential anti-inflammatory effect of enzymatic hydrolysates from Styela clava flesh tissue was assessed via nitric oxide (NO) production in lipopolysaccahride (LPS) induced RAW 264.7 macrophages and in vivo zebrafish model. MATERIALS/METHODS We investigated the ability of enzymatic hydrolysates from Styela clava flesh tissue to inhibit LPS-induced expression of pro-inflammatory mediators in RAW 264.7 macrophages, and the molecular mechanism through which this inhibition occurred. In addition, we evaluated anti-inflammatory effect of enzymatic hydrolysates against a LPS-exposed in in vivo zebrafish model. RESULTS Among the enzymatic hydrolysates, Protamex-proteolytic hydrolysate exhibited the highest NO inhibitory effect and was fractionated into three ranges of molecular weight by using ultrafiltration (UF) membranes (MWCO 5 kDa and 10 kDa). The above 10 kDa fraction down-regulated LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 macrophages. The above 10 kDa fraction suppressed LPS-induced production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, the above 10 kDa fraction inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. Furthermore, NO production in live zebrafish induced by LPS was reduced by addition of the above 10 kDa fraction from S. clava enzymatic hydrolysate. CONCLUSION The results of this study suggested that hydrolysates derived from S. clava flesh tissue would be new anti-inflammation materials in functional resources. PMID:26060532

  1. Anti-inflammatory properties rather than anti-oxidant capability is the major mechanism of neuroprotection by sodium salicylate in a chronic rotenone model of Parkinson's disease.

    PubMed

    Thakur, P; Nehru, B

    2013-02-12

    Parkinson's disease (PD) is the second most common neurodegenerative disorder manifesting in motor, cognitive and behavioral anomalies. Loss of dopaminergic neurons in the substantia nigra region of the brain is the hallmark feature of PD, which is attributed to oxidative and inflammatory stress besides other diverse factors and hence drugs targeting these pathways hold promise as neuro-therapeutics. The anti-oxidative as well as anti-inflammatory properties of sodium salicylate (SS), suggest its neuroprotective potentials in PD. Since PD is a progressive neurodegenerative disorder, the mechanistic basis for utilizing SS as a neuroprotectant in PD could be better understood in the chronic models. The present study utilizes a rotenone-based model of PD to evaluate the neuro-modulatory efficacy of SS. Subcutaneous injection of rotenone (2mg/kg body weight) was given to male SD rats every day, for a period of 5 weeks, which developed all the essential features of PD in these animals. Simultaneously, another group was injected SS intraperitoneally at the dose of 100mg/kg body weight, in addition to the rotenone. In the animals receiving rotenone+SS, significant improvement was observed in the various characteristic hallmarks of PD such as dopamine and tyrosine hydroxylase levels as well as the motor dysfunction symptoms. It attenuated the reactive oxygen species levels significantly but failed to reduce the levels of protein carbonylation and lipid peroxidation. However, SS effectively abridged the levels of inflammatory mediators like cyclooxygenase-2 (COX-2), nuclear factor kappa B and inducible nitric oxide synthase. Correspondingly, a significant decrease in the levels of pro-inflammatory cytokines interleukin-6, interleukin-1β and tumor necrosis factor-α was also observed following SS co-treatment. Thus, neuroprotective efficacy of SS in this chronic model of PD can be largely attributed to its anti-inflammatory effects rather than its free radical

  2. Anti-inflammatory effects of essential oils extracted from Chamaecyparis obtusa on murine models of inflammation and RAW 264.7 cells.

    PubMed

    Park, Yujin; Yoo, Seung-Ah; Kim, Wan-Uk; Cho, Chul-Soo; Woo, Jong-Min; Yoon, Chong-Hyeon

    2016-04-01

    Antimicrobial, antifungal and anti-inflammatory effects of essential oils extracted from Chamaecyparis obtusa (EOCO) have previously been reported. In the present study, the anti-inflammatory effects of EOCO were investigated in two murine models of inflammation: Carrageenan-induced paw edema and thioglycollate-induced peritonitis, and in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The expression levels of proinflammatory cytokines were analyzed by ELISA, the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by western blotting, and nitrite concentration was measured using Griess reagent. In mice with carrageenan-induced edema, paw thickness and the expression levels of interleukin (IL)‑1β and IL-6 in paw homogenates were significantly decreased in the EOCO (5 and 10 mg/kg) group, as compared with the control group. In mice with thioglycollate-induced peritonitis, treatment with EOCO (5 and 10 mg/kg) reduced the number of total cells and suppressed tumor necrosis factor‑α (TNF‑α), IL‑1β and IL‑6 levels in peritoneal fluid. In addition, EOCO reduced nitric oxide, TNF‑α and IL‑6 production, and suppressed iNOS and COX‑2 expression in LPS‑stimulated RAW 264.7 cells. These results suggest that EOCO may exert anti‑inflammatory effects in vivo and in vitro, and that these effects may be associated with the inhibition of inflammatory mediators. Therefore, EOCO may be considered an effective therapeutic agent for the treatment of inflammatory diseases.

  3. Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-κB pathway and reduction of anti-inflammatory mediator expression in the kidney

    PubMed Central

    Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan; Chen, Kejie

    2015-01-01

    Nickel (Ni) or Ni compounds target a number of organs and produce multiple toxic effects. Kidney is the major organ for Ni accumulation and excretion. There are no investigations on the Ni- or Ni compounds-induced renal inflammatory responses in human beings and animals at present. Therefore, we determined NiCl2-caused alteration of inflammatory mediators, and functional damage in the broiler's kidney by the methods of biochemistry, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Dietary NiCl2 in excess of 300 mg/kg caused the renal inflammatory responses that characterized by increasing mRNA expression levels of the pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) via the activation of nucleic factor κB (NF-κB), and decreasing mRNA expression levels of the anti-inflammatory mediators including interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-13 (IL-13). Concurrently, NiCl2 caused degeneration, necrosis and apoptosis of the tubular cells, which was consistent with the alteration of renal function parameters including elevated alkaline phosphatase (AKP) activity, and reduced activities of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), calcium adenosine triphosphatase (Ca2+-ATPase), lactic dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) in the kidney. The above-mentioned results present that the activation of NF-κB pathway and reduction of anti-inflammatory mediator expression are main mechanisms of NiCl2-caused renal inflammatory responses and that the renal function is decreased or impaired after NiCl2-treated. PMID:26417933

  4. Determination of Teloschistes flavicans (sw) norm anti-inflammatory activity

    PubMed Central

    Pereira, Eugênia C.; da Silva, Nicácio H.; Santos, Renata Almeida; Sudário, Ana Patrícia Paiva; Rodrigues e Silva, Antonio Alfredo; de Sousa Maia, Maria Bernadete

    2010-01-01

    Background: Lichens produce a variety of substances that possesses pharmacological actions. However, rare products are submitted to rigorous scientific tests or have the risk potential or side effects evaluated. The lack of medical and sanitary control, absence of accurate botanical identification or purity certification, founded in diverse natural products, may represent great danger to population health. This work aimed to evaluate toxic effects and anti-inflammatory action in vivo of Teloschistes flavicans (Sw.) Norm. (TFN) unrefined extracts, as well as determinate its main constituents. Methods: The carrageenan induced paw edema and cotton pellet implant induced granuloma methods were utilized, besides a classic acute toxicity test. TFN acetone extract inhibited carrageenan paw edema on 60, 120, and 180 min (inhibition percentiles of 45.03%, 60.59% and 41.72%). Results: TFN ethereal (inhibition percentiles of 23.95% and 29.01%) and chloroform (inhibition percentiles of 28.8% and 22.04%) extracts inhibited edema on 120 and 180 min. None of the extract inhibited the granuloma development. None of the extract caused death or other acute toxicity signs. Vicanicine (60.26% in ethereal extract and 51.17% in acetone extract), parietine (9.60% in ethereal extract and 15.38% on second), falacinol (0.78% in ether and 14.95% in acetone) and very low concentration of falacinal (0.15% in ethereal extract and 3.32% in acetone extract) were detected in the medicine. Conclusions: The tested extracts have antiedematogenic activity, but are not effective on subchronic inflammation. The extracts do not present toxic effects in administered doses. PMID:21808568

  5. Anti-Inflammatory Effect of Taurine in Burned Patients

    PubMed Central

    Lak, Sima; Ostadrahimi, Alireza; Nagili, Behrooz; Asghari-Jafarabadi, Mohammad; Beigzali, Sanaz; Salehi, Feridoon; Djafarzadeh, Roxana

    2015-01-01

    Purpose: Burn induced inflammatory response can be mediated by reactive oxygen metabolites and accompanied by multiple organ dysfunction. Taurine has protective effects against various inflammatory conditions. The aim of this study was to determine the effect of Taurine supplement in thermal burn victims. Methods: Thirty patients with severe thermal burns were enrolled in this randomized double-blinded clinical trial. These patients were randomly divided into two equal groups (namely Control and Taurine groups), where both received isocaloric and isonitrogenous formula. One group was supplemented with 50 mg/kg of Taurine per day for a duration of 10 days. Blood samples were obtained to measure Interleukin-10 (IL-10), high-sensitivity C-reactive protein (hs-CRP), and Tumor Necrosis Factor alpha (TNF-α) levels at the beginning and the end of the study. Results: Change in serum level of IL-10 in Taurine group was more than Control group [-13.60(-31.40, -10.40) compared to -4.00(-20.00, -0.20) respectively; P = 0.030]. This change was significant in patients with more than 30% TBSA of burn [-14.20(-31.40, -10.40) compared to -2.40(-9.60, 0.40) respectively; P = 0.013]. As for the hs-CRP and TNF-α levels, the difference between the two groups were not significant. Conclusion: Based on the results obtained, Taurine supplement showed a positive outcome on anti-inflammatory cytokine IL-10 in all burn patients. This effect was even more significant in patients with higher percentage of burn area. Taurine had no significant effect on the inflammatory marker hs-CRP and the pro-inflammatory cytokine TNF-α level. For a more thorough verification, measurement of a wider range of inflammatory cytokines in more frequent time intervals are suggested. PMID:26819926

  6. Anti-inflammatory ergostanes from the basidiomata of Antrodia salmonea.

    PubMed

    Shen, Chien-Chang; Wang, Yea-Hwey; Chang, Tun-Tschu; Lin, Lie-Chwen; Don, Ming-Jaw; Hou, Yu-Chang; Liou, Kuo-Tong; Chang, Shiou; Wang, Wen-Yen; Ko, Han-Chieh; Shen, Yuh-Chiang

    2007-09-01

    Three new anti-oxidative ergostanes, methyl antcinate L (1), antcin M (2), and methyl antcinate K (3), together with nine additional known compounds, 3-ketodehydrosulphurenic acid, sulphurenic acid, dehydrosulphurenic acid, 3beta,15alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid, zhankuic acid A, zhankuic acid B, zhankuic acid C, antcin C, and antcin K were isolated from the basidiomata of Antrodia salmonea, a newly identified species of Antrodia (Polyporaceae) in Taiwan. These three new compounds were identified as methyl 3alpha,7alpha,12alpha-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (1), 3alpha,12alpha-dihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oic acid (2), and methyl 3alpha,4beta,7beta-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (3) by spectroscopic analysis. We studied their antioxidative potential on the production of reactive oxygen species and nitric oxide (NO) in neutrophils and microglial cells, respectively. Compounds 1-3 displayed potent antioxidative activity with IC50 values of around 2.0-8.8 microM that was partially due to inhibition (6-67%) of NADPH oxidase activity but not through direct radical-scavenging properties. Compounds 1-3 also inhibited NO production with IC50 values of around 1.7-16.5 microM and were more potent than a non-specific NOS inhibitor. We conclude that these three new compounds 1, 2, and 3 exhibit anti-inflammatory activities in activated inflammatory cells.

  7. Anti-inflammatory effect of Momordica charantia in sepsis mice.

    PubMed

    Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

    2014-08-21

    Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis.

  8. Cyclooxygenase-2 Inhibitory and Antioxidant Compounds from the Truffle Elaphomyces granulatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ethanol extract of fruiting bodies of Elaphomyces granulatus, a truffle-like fungus, was evaluated for cyclooxygenase-2 (COX-2) enzyme inhibitory and antioxidant activities. Inhibition of COX-2 activity was evaluated in mouse macrophages (RAW 264.7). The extract of E. granulatus caused a 68% inh...

  9. To Extinguish the Fire from Outside the Cell or to Shutdown the Gas Valve Inside? Novel Trends in Anti-Inflammatory Therapies

    PubMed Central

    Marcuzzi, Annalisa; Piscianz, Elisa; Valencic, Erica; Monasta, Lorenzo; Vecchi Brumatti, Liza; Tommasini, Alberto

    2015-01-01

    Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, allowing the specific targeting of single cytokines. They are very effective in extinguishing inflammation from outside the cell, even with the risk of an excessive and prolonged immunosuppression. Small molecules can enter the cell and shutdown the valve of inflammation by directly targeting signal proteins involved in cytokine release or in response to cytokines. They are orally-administrable drugs whose dosage can be easily adjusted to obtain the desired anti-inflammatory effect. This could make these drugs more suitable for a wide range of diseases as stroke, gout, or neurological impairment, where inflammatory activation plays a pivotal role as trigger. Autoinflammatory diseases, which have previously put anti-cytokine proteins in the limelight, can again provide a valuable model to measure the real potential of small inhibitors as anti-inflammatory agents. PMID:26370962

  10. To Extinguish the Fire from Outside the Cell or to Shutdown the Gas Valve Inside? Novel Trends in Anti-Inflammatory Therapies.

    PubMed

    Marcuzzi, Annalisa; Piscianz, Elisa; Valencic, Erica; Monasta, Lorenzo; Vecchi Brumatti, Liza; Tommasini, Alberto

    2015-09-07

    Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, allowing the specific targeting of single cytokines. They are very effective in extinguishing inflammation from outside the cell, even with the risk of an excessive and prolonged immunosuppression. Small molecules can enter the cell and shutdown the valve of inflammation by directly targeting signal proteins involved in cytokine release or in response to cytokines. They are orally-administrable drugs whose dosage can be easily adjusted to obtain the desired anti-inflammatory effect. This could make these drugs more suitable for a wide range of diseases as stroke, gout, or neurological impairment, where inflammatory activation plays a pivotal role as trigger. Autoinflammatory diseases, which have previously put anti-cytokine proteins in the limelight, can again provide a valuable model to measure the real potential of small inhibitors as anti-inflammatory agents.

  11. Non-steroidal anti-inflammatory drug gastropathy: causes and treatment.

    PubMed

    Hawkey, C J

    1996-01-01

    Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) almost invariably cause acute gastroduodenal injury and probably account for approximately 12,000 ulcer bleeding episodes and 1200 deaths per annum in the United Kingdom. Clinically significant intestinal toxicity is also recognized but less clearly defined. The main risk factors for NSAID-related peptic ulcer complications are age, past history, use of higher risk individual NSAIDs, drug dose, concurrent use of warfarin or corticosteroids. The underlying reason for NSAID use and Helicobacter pylori status is not clearly associated with increased risk. Whether NSAIDs cause drug-induced non-ulcer dyspepsia is also controversial. Acute injury occurs more readily with aspirin than with non-aspirin NSAIDs, and the spectrum of acute injury is of little value in predicting clinically significant end points in comparison with different NSAIDs. However, acute studies of co-prescribed protective agents are highly predictive of performance in clinical practice. Gastric mucosal integrity is maintained by the interplay of three protective networks: prostaglandin synthesis, nitric oxide synthesis and the activity of the enteric nervous system. Aspirin and NSAIDs act by inhibiting prostaglandin synthesis catalysed by two cyclooxygenase enzymes. Most existing NSAIDs are unselective and inhibit the activity of the constitutive cyclooxygenase (COX) 1 enzyme in the stomach as much as the cyclooxygenase (COX) 2 enzyme which is induced at sites of inflammation such as joint disease. There are, however, prospects for selective cyclooxygenase 2 inhibitors. Some NSAIDs, particularly aspirin, have additional topical toxicity, which may in part reflect mucosal trapping. Some data favor an effect of NSAIDs in inhibiting mitochondrial oxidative phosphorylation. The principal physiological mechanisms which are compromised by NSAID use are mucosal blood flow, secretion of mucus and bicarbonate and maintenance of a

  12. Induction of hepatic cyclooxygenase-2 by hyperhomocysteinemia via nuclear factor-kappaB activation.

    PubMed

    Wu, Nan; Siow, Yaw L; O, Karmin

    2009-10-01

    Hyperhomocysteinemia, an elevation of blood homocysteine (Hcy), is a metabolic disorder associated with dysfunction of multiple organs. Apart from endothelial dysfunction, Hcy can cause hepatic lipid accumulation and liver injury. However, the mechanism responsible for Hcy-induced liver injury is poorly understood. The aim of this study was to investigate the regulation of cyclooxygenase-2 (COX-2), a proinflammatory factor, expression in the liver during the initial phase of hyperhomocysteinemia. Sprague-Dawley rats were fed a high-methionine diet for 1 or 4 wk. Serum and liver concentrations of Hcy were significantly elevated after 1 or 4 wk of dietary treatment. COX-2 mRNA and protein levels were significantly elevated in the liver of hyperhomocysteinemic rats. The induction of COX-2 expression was more prominent in 1-wk hyperhomocysteinemic rats than that in the 4-wk group. EMSA revealed an activation of NF-kappaB in the same liver tissue in which COX-2 was induced. Administration of a NF-kappaB inhibitor to hyperhomocysteinemic rats effectively abolished hepatic COX-2 expression, inhibited the formation of inflammatory foci, and improved liver function. Further investigation revealed that oxidative stress due to increased superoxide generation was responsible for increased phosphorylation and degradation of IkappaBalpha leading to NF-kappaB activation in the liver. Administration of 4-hydroxy-tetramethyl-piperidine-1-oxyl, an SOD mimetic, to hyperhomocysteinemic rats not only inhibited NF-kappaB activation but also prevented hepatic COX-2 induction and improved liver function. These results suggest that hyperhomocysteinemia-induced COX-2 expression is mediated via NF-kappaB activation. Increased oxidative stress and inflammatory response may contribute to liver injury associated with hyperhomocysteinemia.

  13. Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans

    PubMed Central

    Pialoux, Vincent; Poulin, Marc J.; Hemmelgarn, Brenda R.; Muruve, Daniel A.; Chirico, Erica N.; Faes, Camille; Sola, Darlene Y.; Ahmed, Sofia B.

    2017-01-01

    Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (−20%). Cycloxygenase-2 inhibition significantly limited the increase in 8-hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug. PMID:28344559

  14. Evidence for contributions of interactions of constituents to the anti-inflammatory activity of Hypericum perforatum.

    PubMed

    Hammer, Kimberly D P; Birt, Diane F

    2014-01-01

    Hypericum perforatum (Hp) extracts contain many different classes of constituents including flavonoids and biflavonoids, phloroglucinols, naphthodianthrones, caffeic acid derivatives, and unknown and/or unidentified compounds. Many constituents may be responsible for the anti-inflammatory activity of Hp including quercetin and derivatives, hyperforin, pseudohypericin, and amentoflavone. In line with antidepressant data, it appears that the interactions of constituents may be important for the anti-inflammatory activity of Hp. Interactions of constituents, tested in bioavailability models, may explain why synergistic mechanisms have been found to be important for antidepressant and antiproliferative bioactivities. This review highlights the relationship among individual constituents and the anti-inflammatory activity of Hp extracts and proposes that interactions of constituents may be important for the anti-inflammatory activity of botanical extracts, although the exact mechanisms of the interactions are still unclear.

  15. Anti-Inflammatory Chemical Profiling of the Australian Rainforest Tree Alphitonia petriei (Rhamnaceae).

    PubMed

    Raju, Ritesh; Gunawardena, Dhanushka; Ahktar, Most Afia; Low, Mitchell; Reddell, Paul; Münch, Gerald

    2016-11-11

    Chronic inflammation is an important pathological condition in many human diseases, and due to the side effects of the currently used non-steroidal anti-inflammatory drugs, discovery of novel anti-inflammatory drugs is of general interest. Anti-inflammatory activity guided compound isolation from the plant Alphitonia petriei led to the isolation of the known plant sterols emmolic acid (1), alphitolic acid (2), trans- and cis-coumaroyl esters of alphitolic acid (3 and 4) and betulinic acid (5). A detailed spectroscopic analysis led to the structure elucidation of the alphitolic acid derivatives (1-5), and the semi-synthetic emmolic acid acetate (6). When tested in LPS (Lipopolysaccharides) + IFN-γ (Interferon gamma) activated RAW 264.7 macrophages, all compounds except (1) exhibited potent anti-inflammatory activity (IC50 values as low as 1.7 μM) in terms of downregulation of NO and TNF-α production, but also demonstrated some considerable cytotoxicity.

  16. Anti-inflammatory activity of Dalbergia lanceolaria bark ethanol extract in mice and rats.

    PubMed

    Kale, Mrudula; Misar, A V; Dave, Vivek; Joshi, Maruti; Mujumdar, A M

    2007-06-13

    Topical anti-inflammatory activity of Dalbergia lanceolaria Linn. bark ethanol extract was demonstrated in albino mice using TPA-, EPP- and AA-induced ear edema models. The systemic activity of extract was confirmed using acute and sub-acute anti-inflammatory models in albino rats. The ethanol extract exhibited significant systemic anti-inflammatory activity in Carrageenan-induced rat paw edema, by inhibition of histamine and prostaglandin phases of acute inflammation. The extract also showed significant activity against turpentine-induced exudative changes and no activity against granular tissue formation in cotton pellet-induced granuloma in albino rats. Thus, resultant anti-inflammatory activity might be due to effects on several mediators involving cyclo-oxygenase pathway resulting in prostaglandin formation and leukocyte migration from the vessels.

  17. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities.

    PubMed

    Wang, Yuanyuan; Yang, Xiaorong; Zheng, Xinqiang; Li, Jing; Ye, Chuangxing; Song, Xiaohong

    2010-09-01

    The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.

  18. Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.

    PubMed

    Zughaier, Susu; Karna, Prasanthi; Stephens, David; Aneja, Ritu

    2010-02-11

    Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.

  19. Mechanism of action of flavonoids as anti-inflammatory agents: a review.

    PubMed

    Rathee, Permender; Chaudhary, Hema; Rathee, Sushila; Rathee, Dharmender; Kumar, Vikash; Kohli, Kanchan

    2009-07-01

    Flavonoids are polyphenolic compounds that occur ubiquitously in plants having a variety of biological effects both in vitro and in vivo. They have been found to have antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, anti-neoplastic, mutagenic, antioxidant, antihepatotoxic, antihypertensive, hypolipidemic, antiplatelet and anti-inflammatory activities. Flavonoids also have biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca(+2)-ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. They have been found to have anti-inflammatory activity in both proliferative and exudative phases of inflammation. Several mechanisms of action have been proposed to explain anti-inflammatory action of flavonoids. The aim of the present review is to give an overview of the mechanism of action of potential anti-inflammatory flavonoids.

  20. Phenolic composition, anitproliferative and anti-inflammatory properties of conventional and organic cinnamon and peppermint

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional and organic cinnamon and peppermint were investigated for their phenolic profile, antiproliferative, anti-inflammatory, and antioxidant properties. Accelerated solvent extraction (ASE) with 75% acetone was a better method than Soxhlet and overnight extraction for phenolic content and a...

  1. Anti-inflammatory effects of proanthocyanidin-rich red rice extract via suppression of MAPK, AP-1 and NF-κB pathways in Raw 264.7 macrophages

    PubMed Central

    Yodkeeree, Supachai; Pitchakarn, Pornsiri; Punfa, Wanisa

    2016-01-01

    BACKGROUND/OBJECTIVES Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS Pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B (NF-κB), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-α, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and NF-κB transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced NF-κB and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, NF-κB, and MAPKs pathways. PMID:27247720

  2. Anti-inflammatory and analgesic activities of Chaenomeles speciosa fractions in laboratory animals.

    PubMed

    Li, X; Yang, Y-B; Yang, Q; Sun, L-N; Chen, W-S

    2009-10-01

    The prescription of current existing anti-inflammatory drugs is hampered by their adverse effects over time. Botanical extracts are thought to be a potential source of a natural anti-inflammatory property with fewer adverse effects. Chaenomeles speciosa has long been used as an herbal medicine for treatment of various diseases such as rheumatoid arthritis, prosopalgia, and hepatitis. Until now there have been no reports on the specific anti-inflammatory fractions of extract of C. speciosa (ECS). In the present study the anti-inflammatory activities of different fractions of ECS were evaluated using carrageenan-induced paw edema in rats. The 10% ethanol fraction (C3) was found to have stronger anti-inflammatory effects compared with other fractions at the same dose. We also found that chlorogenic acid was one of the active constituents responsible for the anti-inflammatory effect using bioassay-guided fractionation by means of high-performance liquid chromatography. Compared with controls, fraction C3 demonstrated significant anti-inflammatory activity in the xylene-induced ear edema test (P < .01), acetic acid-induced peritoneal capillary permeability test, and the cotton pellet granuloma test in mice or rats (P < .01); it also showed marked analgesic activity in the acetic acid-induced abdominal contraction test and formalin-induced paw licking test in mice and rats (P < .05 or .01). However, fraction C3 showed no significant effect in the hot plate test in mice. These findings justify the use of the C. speciosa for treating pain and inflammation. These results support the proposal of C. speciosa fraction C3 as a potential anti-inflammatory agent.

  3. Are Anti-Inflammatory Lymphocytes Able to Induce Remission of Breast Cancer

    DTIC Science & Technology

    2006-08-01

    to cancer (1, 2). In humans, infectious inflammation associated with prolonged activation of the host immune system by parasitic , viral, and bacterial...inflammatory CD4+regulatory (TR) cells, as pivotal mediators in human health and disease . We have previously demonstrated that anti- inflammatory TR cells...inflammatory CD4+regulatory (TR) cells, as pivotal mediators in human health and disease (2). Anti- inflammatory TR cells inhibit destructive immune

  4. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology

    PubMed Central

    Pradhan, Swetalina; Madke, Bhushan; Kabra, Poonam; Singh, Adarsh Lata

    2016-01-01

    Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. This study will review anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology. PMID:27688434

  5. Mechanisms for anti-inflammatory effects of 1-[15(S)-hydroxyeicosapentaenoyl] lysophosphatidylcholine, administered intraperitoneally, in zymosan A-induced peritonitis

    PubMed Central

    Hung, Nguyen Dang; Kim, Mee Ree; Sok, Dai-Eun

    2011-01-01

    BACKGROUND AND PURPOSE Lysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti-inflammatory actions. 15-Lipoxygeanation is crucial for anti-inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti-inflammatory actions of 1-(15-hydroxyeicosapentaenoyl)-lysoPC (15-HEPE-lysoPC) and its derivatives were examined in a mechanistic analysis. EXPERIMENTAL APPROACH Anti-inflammatory actions of 15-HEPE-lysoPC in zymosan A-induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines. KEY RESULTS When each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A-induced plasma leakage, 15-HEPE-lysoPC was found to be more potent than 1-(15-hydroperoxyeicosapentaenoyl)-lysoPC or 1-eicosapentaenoyl-lysoPC. Separately, i.p. administration of 15-HEPE-lysoPC markedly inhibited plasma leakage, in contrast to 15-HEPE, which had only a small effect. 15-HEPE-lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC4 and LTB4, 5-lipoxygenation products, as well as the levels of pro-inflammatory cytokines. The time-course study indicated that 15-HEPE-lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15-HEPE-lysoPC administration caused a partial suppression of LTC4-induced plasma leakage and LTB4-induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC-hydrolysing activity, crucial for anti-inflammatory activity, and a system capable of generating lipoxin A from 15-hydroxy eicosanoid precursor. CONCLUSIONS AND IMPLICATIONS 15-HEPE-lysoPC, a precursor for 15-HEPE in target cells, induced anti-inflammatory actions by inhibiting the formation of pro-inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15-HEPE-lysoPC might be one of many potent anti-inflammatory lipids in vivo

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  8. Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

    PubMed

    Theoduloz, Cristina; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Cádiz, Solange; Bustamante, Fernanda; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2015-06-18

    The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes.

  9. Anti-inflammatory and analgesic activities of Edgeworthia chrysantha and its effective chemical constituents.

    PubMed

    Hu, Xiao-Jia; Jin, Hui-Zi; Xu, Wen-Zheng; Chen, Ming; Liu, Xiao-Hua; Zhang, Wei; Su, Juan; Zhang, Chuan; Zhang, Wei-Dong

    2008-09-01

    The barks and roots of Edgeworthia chrysantha LINDL., which have been used as the folk medicine "Zhu shima" in southern China due to their detumescence and acesodyne effects, were investigated for their anti-inflammatory and analgesic activities using a xylene-induced ear edema assay in mice and Freund's complete adjuvant-induced paw edema as inflammation models, and the acetic acid-induced writhing test as an analgesic model. Fractions effective in terms of anti-inflammatory and analgesic activities were obtained from E. chrysantha. The chloroform-soluble fraction (CHF) showed significant anti-inflammatory (p<0.01-0.001) and analgesic (p<0.01) effects. On further purification by silica gel, three major coumarins, edgeworin (EdN), edgeworosides A and C (EdeA and EdeC), were isolated from the chloroform fraction and both anti-inflammatory and analgesic activities were evaluated. EdN and EdeA had anti-inflammatory (p<0.05-0.01) and analgesic (p<0.001) effects, while EdeC only showed an analgesic effect. The results of this study thus demonstrated that the coumarins EdN, EdeA and EdeC in this plant may be active constituents that contribute to the anti-inflammatory and analgesic effects.

  10. Heme oxygenase-1 is dispensable for the anti-inflammatory activity of intravenous immunoglobulin

    PubMed Central

    Galeotti, Caroline; Hegde, Pushpa; Das, Mrinmoy; Stephen-Victor, Emmanuel; Canale, Fernando; Muñoz, Marcos; Sharma, Varun K.; Dimitrov, Jordan D.; Kaveri, Srini V.; Bayry, Jagadeesh

    2016-01-01

    Intravenous immunoglobulin G (IVIG) is used in the therapy of various autoimmune and inflammatory conditions. The mechanisms by which IVIG exerts anti-inflammatory effects are not completely understood. IVIG interacts with numerous components of the immune system including dendritic cells, macrophages, T and B cells and modulate their functions. Recent studies have reported that heme oxygenase-1 (HO-1) pathway plays an important role in the regulation of inflammatory response in several pathologies. Several therapeutic agents exert anti-inflammatory effects via induction of HO-1. Therefore, we aimed at exploring if anti-inflammatory effects of IVIG are mediated via HO-1 pathway. Confirming the previous reports, we report that IVIG exerts anti-inflammatory effects on innate cells as shown by the inhibitory effects on IL-6 and nitric oxide production and confers protection in experimental autoimmune encephalomyelitis (EAE) model. However, these effects were not associated with an induction of HO-1 either in innate cells such as monocytes, dendritic cells and macrophages or in the kidneys and liver of IVIG-treated EAE mice. Also, inhibition of endogenous HO-1 did not modify anti-inflammatory effects of IVIG. These results thus indicate that IVIG exerts anti-inflammatory effects independent of HO-1 pathway. PMID:26796539

  11. Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa

    PubMed Central

    Cruz Paredes, Carla; Bolívar Balbás, Paulina; Juárez, Zaida Nelly; Sánchez Arreola, Eugenio; Hernández, Luis Ricardo

    2013-01-01

    The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae). Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities. PMID:23843731

  12. In vitro antioxidant capacity and anti-inflammatory activity of seven common oats.

    PubMed

    Chu, Yi-Fang; Wise, Mitchell L; Gulvady, Apeksha A; Chang, Tony; Kendra, David F; Jan-Willem van Klinken, B; Shi, Yuhui; O'Shea, Marianne

    2013-08-15

    Oats are gaining increasing scientific and public interest for their purported antioxidant-associated health benefits. Most reported studies focused on specific oat extracts or particular oat components, such as β-glucans, tocols (vitamin E), or avenanthramides. Studies on whole oats with respect to antioxidant and anti-inflammatory activities are still lacking. Here the antioxidant and anti-inflammatory activities from whole oat groats of seven common varieties were evaluated. All oat varieties had very similar oxygen radical absorption capacity compared with other whole grains. In an anti-inflammatory assay, oat variety CDC Dancer inhibited tumor necrosis factor-α induced nuclear factor-kappa B activation by 27.5% at 2 mg/ml, whereas variety Deiter showed 13.7% inhibition at a comparable dose. Avenanthramide levels did not correlate with the observed antioxidant and anti-inflammatory activities. Further investigations are needed to pinpoint the specific antioxidant and anti-inflammatory compounds, and potential synergistic and/or matrix effects that may help explain the mechanisms of oat's anti-inflammatory actions.

  13. [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.

  14. Anti-Inflammatory Activities of Inotilone from Phellinus linteus through the Inhibition of MMP-9, NF-κB, and MAPK Activation In Vitro and In Vivo

    PubMed Central

    Huang, Guan-Jhong; Huang, Shyh-Shyun; Deng, Jeng-Shyan

    2012-01-01

    Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr)-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK) [extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38], and nuclear factor-κB (NF-κB), matrix-metalloproteinase (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α) levels on serum at the 5th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2), NF-κB, and MMP-9 expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the activities of CAT

  15. Bisdemethylcurcumin and Structurally Related Hispolon Analogues of Curcumin Exhibit Enhanced Prooxidant, Anti-Proliferative and Anti-inflammatory Activities in vitro

    PubMed Central

    Ravindran, Jayaraj; Subbaraju, Gottumukkala V.; Ramani, Modukuri V.; Sung, Bokyung; Aggarwal, Bharat B.

    2010-01-01

    Curcumin, a component of turmeric (Curcuma longa), exhibits anti-inflammatory and anti-proliferative activities through the generation of reactive oxygen species (ROS). Curcumin (diferuloylemethane) contains two hydroxyl, two methoxy and two phenyl groups but how these groups contribute to its activity is poorly understood. We synthesized analogues that varied in inclusion of these groups and compared their activity. We found that bisdemethylcurcumin (BDC) was more potent than curcumin as an anti-inflammatory agent as indicated by suppression of TNF-induced NF-κB activation, more potent as an anti-proliferative agent, and more potent in inducing ROS. Hispolon, which lacks one aromatic unit in relation to curcumin, also exhibited enhanced anti-inflammatory and anti-proliferative activities. When synthetic curcumin (Cur-S) was compared with bisdemethylcurcumin (BDC), hispolon, hispolon methyl ether (HME), dehydroxy hispolon (DH), hydroxy hispolon (HH), methoxy hispolon methyl ether (MHME), and methoxy hispolon (MH), we found that following order of anti-inflammatory activity: BDC=Hispolon>HME> HH>Cur-S>MHME>MH>DH; for anti-proliferative Hispolon> BDC>MHME> Cur-S>MH>HME=HH>DH; and for prooxidant BDC>Cur-S=MHME>HH>MH+HME>DH (254-1414 mean fluorescence intensity). Thus dehydroxyhispolon was least potent for all three activities. Overall the results indicates that the substitution of a hydroxyl group for a methoxy group at the meta positions of the phenyl rings in curcumin significantly enhanced the anti-inflammatory activity, and the removal of phenyl ring at the 7th position of the heptadiene back bone and addition of hydroxyl group significantly increased the anti-proliferative activity of curcumin. PMID:20138025

  16. A comparative study on hulled adlay and unhulled adlay through evaluation of their LPS-induced anti-inflammatory effects, and isolation of pure compounds.

    PubMed

    Choi, Goeun; Han, Ah-Reum; Lee, Joo Hee; Park, Ji-Youn; Kang, Unwoo; Hong, Jongki; Kim, Yeong Shik; Seo, Eun-Kyoung

    2015-03-01

    Coicis semen (=the hulled seed of Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf; Gramineae), commonly known as adlay and Job's tears, is widely used in traditional medicine and as a nutritious food. Bioassay-guided fractionation of the AcOEt fraction of unhulled adlays, using measurement of nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, led to the isolation and identification of two new stereoisomers, (+)-(7'S,8'R,7″S,8″R)-guaiacylglycerol β-O-4'-dihydrodisinapyl ether (1) and (+)-(7'S,8'R,7″R,8″R)-guaiacylglycerol β-O-4'-dihydrodisinapyl ether (2), together with six known compounds, 3-8. Compounds 3 and 4 exhibited inhibitory activities on LPS-induced NO production with IC50 values of 1.4 and 3.7 μM, respectively, and suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in RAW 264.7 macrophage cells. Simple high-performance liquid chromatography with ultraviolet detection (HPLC/UV) was used to compare the AcOEt fraction of unhulled adlays responsible for the anti-inflammatory activity in RAW 264.7 cells and the inactive AcOEt fraction of hulled adlays.

  17. High anti-inflammatory activity of harpagoside-enriched extracts obtained from solvent-modified super- and subcritical carbon dioxide extractions of the roots of Harpagophytum procumbens.

    PubMed

    Günther, M; Laufer, S; Schmidt, P C

    2006-01-01

    Solvent-modified carbon dioxide extractions of the roots of Harpagophytum procumbens have been investigated with respect to extraction efficiency and content of harpagoside, and compared with a conventional extract. The effects of pressure, temperature, type and concentration of the modifier have been examined. Two extraction steps were necessary in order to achievehigh anti-inflammatory harpagoside-enriched extracts. The first extraction step was carried out in the supercritical state using carbon dioxide modified with n-propanol to remove undesired lipophilic substances. The main extraction was performed either in the supercritical or in the subcritical state with carbon dioxide modified with ethanol. The supercritical fluid extraction resulted in extracts containing up to 30% harpagoside. The subcritical extracts showed a harpagoside content of ca. 20%, but the extraction yield was nearly three times greater compared with supercritical conditions. The total harpagoside recovery resulting from the sum of the extract and the crude drug residue was greater than 99% in all experiments. The conventional extract and two carbon dioxide extracts were tested for in-vitro inhibition of 5-lipoxygenase or cyclooxygenase-2 biosynthesis. Both carbon dioxide extracts showed total inhibition on 5-lipoxygenase biosynthesis at a concentration of 51.8 mg/L. In contrast, the conventional extract failed to show any inhibition of 5-lipoxygenase biosynthesis.

  18. 4,2',5'-trihydroxy-4'-methoxychalcone from Dalbergia odorifera exhibits anti-inflammatory properties by inducing heme oxygenase-1 in murine macrophages.

    PubMed

    Lee, Dong-Sung; Li, Bin; Im, Nam-Kyung; Kim, Youn-Chul; Jeong, Gil-Saeng

    2013-05-01

    Dalbergia odorifera T. Chen (Leguminosae) has traditionally been used as an ingredient in East Asian medicines to treat various diseases. In the present study, 4,2',5'-trihydroxy-4'-methoxychalcone (TMC), a biologically active chalcone isolated from the heartwood of D. odorifera, inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-induced prostaglandin E2 (PGE2) and iNOS-induced nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Furthermore, TMC suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production, and the phosphorylation and degradation of IκB-α as well as the LPS-stimulated nuclear translocation of p65 in macrophages. The present study also demonstrated that TMC induced heme oxygenase-1 (HO-1) expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of TMC on LPS-induced NO, PGE2, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β production were partially reversed by the HO inhibitor tin protoporphyrin (SnPP). These results suggest that TMC inhibits pro-inflammatory mediators by inducing the expression of anti-inflammatory HO-1 via the Nrf2 pathway.

  19. Artificial sweetener neohesperidin dihydrochalcone showed antioxidative, anti-inflammatory and anti-apoptosis effects against paraquat-induced liver injury in mice.

    PubMed

    Shi, Qiong; Song, Xiufang; Fu, Juanli; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang

    2015-12-01

    The present study evaluated the protective effect of artificial sweetener neohesperidin dihydrochalcone (NHDC) against paraquat (PQ)-induced acute liver injury in mice. A single dose of PQ (75mg/kg body weight, i.p.) induced acute liver toxicity with the evidences of increased liver damage biomarkers, aspartate transaminase (AST) and alanine transaminase (ALT) activities in serum. Consistently, PQ decreased the antioxidant capacity by reducing glutathione peroxidase (GP-X), glutathione-S-transferase (GST) and catalase (CAT) activities, glutathione (GSH) level and total antioxidant capacity (T-AOC), as well as increasing reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels. Histopathological examination revealed that PQ induced numerous changes in the liver tissues. Immunochemical staining assay indicated the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. However, NHDC ameliorates PQ-induced hepatic toxicity in mice by reversing these parameters. Additionally, NHDC significantly inhibited PQ-induced nuclear factor-kappa B (NF-κB) expression and mitochondrial-driven apoptotic signaling. TUNEL assay confirmed that PQ-induced apoptosis was relieved by NHDC. In conclusion, these findings suggested that NHDC showed potent antioxidant, anti-inflammatory and anti-apoptotic effects against PQ-induced acute liver damage.

  20. Anti-inflammatory effects of the Zingiber officinale roscoe constituent 12-dehydrogingerdione in lipopolysaccharide-stimulated Raw 264.7 cells.

    PubMed

    Han, Young Ah; Song, Chang Woo; Koh, Woo Suk; Yon, Gyu Hwan; Kim, Young Sup; Ryu, Shi Yong; Kwon, Hoon Jeong; Lee, Kyu Hong

    2013-08-01

    Ginger has long been used worldwide as a spice, seasoning, and wine and is also used as a traditional medicine. There have been no previous studies of the potential beneficial effects of the ginger constituent 12-dehydrogingerdione (12-DHGD). We investigated the anti-inflammatory effect of 12-DHGD on lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. The cytotoxicity of 12-DHGD was measured using the MTT assay, and production of prostaglandin E2 (PGE2 ) and the inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was measured by ELISA. Production of nitric oxide (NO) was measured using Griess reagent and expression of cyclooxygenase-2 (COX-2) and inducible NO (iNOS) enzymes was assessed by reverse transcriptase-polymerase chain reaction. Treatment of Raw 264.7 cells with 12-DHGD significantly inhibited LPS-stimulated production of NO (at 12-DHGD concentrations of 150 and 200 ng/ml), IL-6 (at 50, 100, 150, and 200 ng/ml), and PGE2 (at 200 ng/ml). Consistent with the effects on NO and PGE2 production, 12-DHGD treatment also inhibited the LPS-stimulated increase in iNOS and COX-2 mRNA levels. However, 12-DHGD did not affect production of IL-1β or TNF-α in response to LPS. 12-DHGD, a constituent of ginger, is a potent inhibitor of proinflammatory mediator production in Raw 264.7 macrophage cells.

  1. Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-α and IL-1.

    PubMed

    Kim, Ho-Joong; Yeom, Jin S; Koh, Yong-Gon; Yeo, Jee-Eun; Kang, Kyoung-Tak; Kang, Young-Mi; Chang, Bong-Soon; Lee, Choon-Ki

    2014-04-01

    The purpose of this study was to investigate the anti-inflammatory effect of platelet-rich plasma (PRP) with collagen matrix on human nucleus pulposus (NP) cell in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). NP cells from human disks were cultured in a monolayer and maintained in the collagen matrix prior to the addition of recombinant human IL-1 and TNF-α. After applying IL-1 and TNF-α, PRP prepared by using a commercially available platelet concentration system was added. The response was investigated using real-time PCR for mRNA expression of type II collagen, aggrecan, matrix metalloproteinase-3 (MMP-3), and cyclooxygenase-2 (COX-2). The combination of IL-1β and TNF-α led to decrease of matrix synthesis gene expression such as collagen type II and aggrecan and increase of the degradation gene expression of COX-2 and MMP-3, compared to the control. Consecutive PRP exposure significantly recovered the down-regulated gene expression of collagen type II and aggrecan and significantly reduced the increased MMP-3 and COX-2 gene expression, compared to that of control groups with pro-inflammatory cytokines. The administration of PRP with collagen matrix markedly suppressed cytokine-induced pro-inflammatory degrading enzymes and mediators in the NP cell. It also rescued gene expression concerning matrix synthesis, thereby stabilizing NP cell differentiation.

  2. Structure-based QSAR study on differential inhibition of human prostaglandin endoperoxide H synthase-2 (COX-2) by nonsteroidal anti-inflammatory drugs.

    PubMed

    Pouplana, R; Lozano, J J; Pérez, C; Ruiz, J

    2002-10-01

    The prostaglandin-endoperoxide H synthase-1 (PGHS- 1) and prostaglandin-endoperoxide H synthase-2 (PGHS-2) are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs). It appears that the high degree of selectivity for inhibition of PGHS-2 shown by certain compounds is the result of two mechanisms (time-dependent, time-independent inhibition), by which they interact with each isoform. Molecular models of the complexes formed by indomethacin, sulindac, fenamates, 2-phenylpropionic acids and selective cyclooxygenase-2 (COX-2) inhibitors with the cyclooxygenase active site of human PGHS-2 have been built, paying particular attention to water molecules that participate in the hydrogen-bonding network at the polar active site entrance. The stability of the complexes has been assessed by molecular dynamics simulations and interaction energy decomposition analysis, and their biological significance has been discussed in light of available X-ray crystallographic and kinetic results. The selective PGHS-2 inhibitors exploit the extra space of a side-pocket in the active site of PGHS-2 that is not found in PGHS-1. The results suggest that active site hydration together with residues Tyr355, Glu524, Arg120 and Arg513 are crucial to understand the time-dependent inhibition mechanism. A marked relationship between the isoform selectivity and tightly interactions with residues into the side pocket bordered by Val523 is also found.

  3. Molecular modelling of the differential interaction between several non-steroidal anti-inflammatory drugs and human prostaglandin endoperoxide H synthase-2 (h-PGHS-2).

    PubMed

    Pouplana, R; Lozano, J J; Ruiz, J

    2002-01-01

    The prostaglandin endoperoxide H synthase-1 (PGHS-1) and prostaglandin endoperoxide H synthase-2 (PGHS-2) are the targets of non-steroidal anti-inflammatory drugs (NSAIDs). The high degree of selectivity for inhibition of PGHS-2 shown by certain compounds appears to stem from two mechanisms (time-dependent, time-independent inhibition) by which they interact with each isoform. Molecular models of the complexes between indomethacin, fenamates, 2-phenylpropionic acids and the selective cyclooxygenase-2 (COX-2) inhibitors, with the cyclooxygenase active site of human PGHS-2 have been built by combining homology modelling, conformational searching and automated docking techniques. The stability of the resulting complexes has been assessed by molecular dynamics simulations combined with extended linear response calculations. The results allow us to identify regions of biological significance consistent with both X-ray crystallographic and kinetic results. The selective PGHS-2 inhibitors exploit the extra space of a side-pocket in the active site of PGHS-2 that is not found in PGHS-1. The results obtained point out a marked relationship between the experimental affinity and the electrostatic interaction energy alone for a series of NSAIDs. Analysis of the structural and the energetic data provides evidence supporting that network of hydrogen bonds between Tyr355, Glu524, Arg120 and Arg513 might be involved in mediating the binding of the time-dependent inhibitors of PGHS-2.

  4. Anti-inflammatory effect of auraptene extracted from trifoliate orange (Poncirus trifoliate) on LPS-stimulated RAW 264.7 cells.

    PubMed

    Yan, Huiqing; Ma, Zhaocheng; Peng, Shu'ang; Deng, Xiuxin

    2013-12-01

    Poncirus trifoliate is a traditional Chinese medicinal plant used for treating inflammation-related diseases for a long time and trifoliate orange contains abundant auraptene. The present study was to evaluate auraptene as a potential anti-inflammatory agent and investigate the mechanism of auraptene against prostaglandins E2 (PGE2) and cyclooxygenase-2 (COX-2) on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by comparing it with aspirin as a positive control group. The methods of enzyme-linked immunosorbent assay, reverse transcriptive polymerase chain reaction, real-time PCR, and western-blotting were used in the study. The results showed that auraptene exhibited better biocompatibility and lower cytotoxicity. At the same time, it significantly inhibited the production of PGE2 on LPS-stimulated macrophage cells. The auraptene-treated group had a higher COX-2 mRNA expression but relatively lower COX-2 protein level which implied that auraptene suppressed the post-transcriptional expression of COX-2 protein but not the transcriptional process. Compared with aspirin, the lower cytotoxicity of auraptene can make it a potential source for medicine that can benefit patients who are suffering from chronic inflammatory diseases and need long-term medication.

  5. Impact of cooking and digestion, in vitro, on the antioxidant capacity and anti-inflammatory activity of cinnamon, clove and nutmeg.

    PubMed

    Baker, Iona; Chohan, Magali; Opara, Elizabeth I

    2013-12-01

    The impact of cooking and digestion on the antioxidant capacity (AC), estimated total phenolic content (TPC) and anti-inflammatory activity (AA) of culinary spices was determined to investigate their significance as dietary contributors to these properties. Extracts of uncooked (U), cooked (C) and cooked and digested, in vitro, (D) cinnamon, clove and nutmeg were prepared and the TPC, AC and AA, specifically the inhibition of cyclo-oxygenase 2 (COX-2) and the amount of prostaglandin (PG) synthesized, were determined. Compared to their uncooked (U) counterparts, the following changes were statistically significant: the AC and TPC for (C) clove, and the TPC for (D) clove decreased, the TPC for (D) clove increased, the TPC for (C) nutmeg increased, and the AC and TPC for (D) nutmeg increased, and the TPC for (C) and (D) nutmeg increased. All the spices achieved near 100 % inhibition of COX-2 which was associated with the inhibition of the amount of PG synthesized. Based on estimated levels of ingestion, cinnamon possesses a much higher AC than clove and nutmeg because it is typically used in larger quantities. For AA, (U, C and D) cinnamon and clove maintain near 100 % inhibition of COX-2 but only the inhibitory potential of (D) nutmeg could be ascertained (70 %). Cooking and digestion alter the TPC and AC of these spices although the changes are not consistent between spices or across treatments. In contrast to AC, significant AA is likely to be present in these spices at amounts used in cooking.

  6. Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study.

    PubMed

    Brasky, Theodore M; Bonner, Matthew R; Moysich, Kirsten B; Ochs-Balcom, Heather M; Marian, Catalin; Ambrosone, Christine B; Nie, Jing; Tao, Meng Hua; Edge, Stephen B; Trevisan, Maurizio; Shields, Peter G; Freudenheim, Jo L

    2011-02-01

    Chronic inflammation has been consistently associated with cancers of several sites, including the breast, and inhibition of inflammation through the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with risk. As NSAIDs bind with cyclooxygenase-2 (COX-2), genetic variation in COX-2 may influence breast cancer risk by affecting inflammatory response and response to NSAID use. We identified eight single nucleotide polymorphisms (SNPs) for COX-2 and examined their association with risk of breast cancer in a population-based case-control study in Western New York. Cases had incident, first primary, histologically confirmed breast cancer (n = 1077). Controls (n = 1910) were randomly selected from NY Department of Motor Vehicles records (< 65) or Medicare rolls (≥ 65). Participants were queried on adult lifetime use of aspirin and recent use of ibuprofen. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). One SNP, rs2745559, was associated with an increased risk of breast cancer (OR 1.23, 95% CI 1.03-1.46). Associations with other variants were not evident. Significant interaction (P interaction = 0.04) between recent aspirin use and rs4648261 was also observed. Variation in COX-2 was modestly associated with breast cancer risk, indicating that COX-2 may play a role in breast carcinogenesis. Better understanding of the role of COX-2 genetic variation and interaction with NSAID use in breast carcinogenesis has potential to inform prevention strategies.

  7. Suppression of Transglutaminase-2 is Involved in Anti-Inflammatory Actions of Glucosamine in 12-O-Tetradecanoylphorbol-13-Acetate-Induced Skin Inflammation

    PubMed Central

    Cho, Sun A; Lee, Hye Ja; Lee, Eun Ji; Kang, June Hee; Kim, You Lee; Kim, Hyun Ji; Oh, Seung Hyun; Choi, Changsun; Lee, Ho; Kim, Soo Youl

    2012-01-01

    Glucosamine (GS) is well known for the treatment of inflam-mation. However, the mechanism and efficacy of GS for skin inflammation are unclear. The aim of this study was to evaluate the effects and mechanism of GS in the mouse 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema model. TPA-induced ear edema was evoked in ICR or transglutaminase 2 (Tgase-2) (-/-) mice. GS was administered orally (10-100 mg/kg) or topically (0.5-2.0 w/v %) prior to TPA treatment. Orally administered GS at 10 mg/kg showed a 76 or 57% reduction in ear weight or myeloperoxidase, respectively, and a decreased expression of cyclooxy-genase-2 (COX-2), NF-κB and Tgase-2 in TPA-induced ear edema by western blot and immunohistochemistry. Role of Tgase-2 in TPA ear edema is examined using Tgase-2 (-/-) mice and TPA did not induce COX-2 expression in ear of Tgase-2 (-/-) mice. These observations suggested that Tgase-2 is involved in TPA-induced COX-2 expression in the inflamed ear of mice and anti-inflammatory effects of glucosamine is mediated through suppression of Tgase-2 in TPA ear edema. PMID:24009824

  8. An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity via down-regulation of nitric oxide.

    PubMed

    Ganguly, Sudipto; Mula, Soumyaditya; Chattopadhyay, Subrata; Chatterjee, Mitali

    2007-05-01

    The leaves of Piper betle (locally known as Paan) have long been in use in the Indian indigenous system of medicine for the relief of pain; however, the underlying molecular mechanisms of this effect have not been elucidated. The anti-inflammatory and immunomodulatory effects of an ethanolic extract of the leaves of P. betle (100 mg kg(-1); PB) were demonstrated in a complete Freund's adjuvant-induced model of arthritis in rats with dexamethasone (0.1 mg kg(-1)) as the positive control. At non-toxic concentrations of PB (5-25 microg mL(-1)), a dose-dependent decrease in extracellular production of nitric oxide in murine peritoneal macrophages was measured by the Griess assay and corroborated by flow cytometry using the nitric oxide specific probe, 4,5-diaminofluorescein-2 diacetate. This decreased generation of reactive nitrogen species was mediated by PB progressively down-regulating transcription of inducible nitric oxide synthase in macrophages, and concomitantly causing a dose-dependent decrease in the expression of interleukin-12 p40, indicating the ability of PB to down-regulate T-helper 1 pro-inflammatory responses. Taken together, the anti-inflammatory and anti-arthrotic activity of PB is attributable to its ability to down-regulate the generation of reactive nitrogen species, thus meriting further pharmacological investigation.

  9. A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis.

    PubMed

    Boilard, Eric; Lai, Ying; Larabee, Katherine; Balestrieri, Barbara; Ghomashchi, Farideh; Fujioka, Daisuke; Gobezie, Reuben; Coblyn, Jonathan S; Weinblatt, Michael E; Massarotti, Elena M; Thornhill, Thomas S; Divangahi, Maziar; Remold, Heinz; Lambeau, Gérard; Gelb, Michael H; Arm, Jonathan P; Lee, David M

    2010-05-01

    Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation.

  10. A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis

    PubMed Central

    Boilard, Eric; Lai, Ying; Larabee, Katherine; Balestrieri, Barbara; Ghomashchi, Farideh; Fujioka, Daisuke; Gobezie, Reuben; Coblyn, Jonathan S; Weinblatt, Michael E; Massarotti, Elena M; Thornhill, Thomas S; Divangahi, Maziar; Remold, Heinz; Lambeau, Gérard; Gelb, Michael H; Arm, Jonathan P; Lee, David M

    2010-01-01

    Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation. PMID:20432503

  11. Anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile, a synthetic arvelexin derivative, on the macrophages through destabilizing mPGES-1 mRNA and suppressing NF-κB activation.

    PubMed

    Shin, Ji-Sun; Choi, Hye-Eun; Kim, Soo-Dong; Lee, Yong Sup; Cho, Young-Wuk; Lee, Kyung Tae

    2014-12-05

    We previously demonstrated that 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin, showed the strong inhibitory effects on LPS-induced NO and PGE2 production in macrophages. In this study, we focused on elucidating the anti-inflammatory properties of 7-HMIA and the mechanisms involved using in vitro and in vivo experimental models. In LPS-induced RAW 264.7 macrophages, 7-HMIA significantly inhibited the release of proinflammatory mediators such as prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). We also found that 7-HMIA suppressed PGE2 production not by inhibiting cyclooxygenase-2 (COX-2) expression or activity, but rather by suppressing the mRNA stability of microsomal prostaglandin E synthase (mPGES-1). Furthermore, 7-HMIA mediated attenuation of inducible NO synthase (iNOS), TNF-α, and IL-6 was closely associated with suppression of transcriptional activities of nuclear factor-kappa B (NF-κB), by decreasing p65 nuclear translocation and Akt phosphorylation. Animal studies revealed that 7-HMIA potently suppressed the carrageenan-induced paw edema and myeloperoxidase (MPO) activity in paw tissues. Taken together, our data indicated that the molecular basis for the anti-inflammatory properties of 7-HMIA involved the inhibition of mRNA stability of mPGES-1 and PI3K/Akt-mediated NF-κB pathways.

  12. Anti-inflammatory effects of ethanolic extract of Antrodia salmonea in the lipopolysaccharide-stimulated RAW246.7 macrophages and the λ-carrageenan-induced paw edema model.

    PubMed

    Huang, Guan-Jhong; Pan, Chun-Hsu; Liu, Fon-Chang; Wu, Tian-Shung; Wu, Chieh-Hsi

    2012-05-01

    The purpose of this study was to examine anti-inflammatory effect of ethanolic extract of Antrodia salmonea (EAS) in the lipopolysaccharide (LPS)-stimulated RAW246.7 macrophages and the carrageenan (Carr)-induced edema paw model, and to clarify its possible molecular mechanisms. Inhibitory effects of EAS were examined on cells proliferation, nitric oxide (NO) production, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, and activity of antioxidant enzymes. Our data demonstrated that EAS inhibited cell growth, NO production, and expression of iNOS and COX-2 proteins in LPS-stimulated RAW246.7 cells. EAS can also significantly reduce paw edema, content of NO, TNF-α and malondialdehyde (MDA), expression of iNOS and COX-2 proteins, and neutrophil infiltration within the tissues stimulated by Carr. The anti-inflammatory mechanisms of EAS might be related to the decrease of inflammatory cytokine and increase of antioxidant enzymes activities, which would result in reduction of iNOS, COX-2 and MDA and subsequently inflammatory responses.

  13. The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells.

    PubMed

    Li, Rui-Jun; Gao, Cai-Yun; Guo, Chao; Zhou, Miao-Miao; Luo, Jun; Kong, Ling-Yi

    2016-12-02

    Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E2 (PGE2), and several pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Further research indicated that they downregulated the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, they also suppressed nuclear translocation of NF-κB p65, phosphorylation of STAT3, and upregulated HO-1 expression. Intriguingly, the activation of MAPKs was suppressed by WA but was not altered by WC. Taken together, these data provide scientific evidence for elucidating the major bioactive constituents and related molecular mechanisms for the traditional use of P. minima and suggest that WA and WC can be attractive therapeutic candidates for various inflammatory diseases.

  14. Carnosic Acid Induces Anti-Inflammatory Effects in Paraquat-Treated SH-SY5Y Cells Through a Mechanism Involving a Crosstalk Between the Nrf2/HO-1 Axis and NF-κB.

    PubMed

    de Oliveira, Marcos Roberto; de Souza, Izabel Cristina Custódio; Fürstenau, Cristina Ribas

    2017-01-12

    Carnosic acid (CA) is a phenolic diterpene obtained from Rosmarinus officinalis L. and has demonstrated cytoprotective properties in several experimental models. CA exerts antioxidant effects by upregulating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which controls the expression of antioxidant and phase II detoxification enzymes. Heme oxygenase-1 (HO-1) expression is modulated by Nrf2 and has been demonstrated as part of the mechanism underlying the CA-induced cytoprotection. Nonetheless, it remains to be studied whether and how HO-1 would mediate CA-elicited anti-inflammatory effects. Therefore, we have investigated here whether and how CA would prevent paraquat (PQ)-induced inflammation-related alterations in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were pretreated for 12 h with CA at 1 μM before exposure to PQ for further 24 h. CA suppressed the PQ-induced alterations on the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) through a mechanism involving the activation of the Nrf2/HO-1 axis. Furthermore, we observed a crosstalk between the Nrf2/HO-1 signaling pathway and the activation of the nuclear factor-κB (NF-κB) transcription factor, since administration of ZnPP IX (specific inhibitor of HO-1) or Nrf2 knockdown using small interfering RNA (siRNA) abolished the anti-inflammatory effects induced by CA. Moreover, administration of SN50 (specific inhibitor of NF-κB) inhibited the PQ-induced inflammation-related effects in SH-SY5Y cells. Therefore, CA exerted anti-inflammatory effects in SH-SY5Y cells through an Nrf2/HO-1 axis-dependent manner associated with downregulation of NF-κB.

  15. Ethanol Extract of Peanut Sprout Exhibits a Potent Anti-Inflammatory Activity in Both an Oxazolone-Induced Contact Dermatitis Mouse Model and Compound 48/80-Treated HaCaT Cells

    PubMed Central

    Choi, Da-In; Choi, Jee-Young; Kim, Young Jee; Lee, Jee-Bum; Kim, Sun-Ouck; Shin, Hyong-Taek

    2015-01-01

    Background We developed an ethanol extract of peanut sprouts (EPS), a peanut sprout-derived natural product, which contains a high level of trans-resveratrol (176.75 µg/ml) and was shown to have potent antioxidant activity. Objective We evaluated the potential anti-inflammatory activity of EPS by measuring its antioxidant potential in skin. Methods The anti-inflammatory activity of EPS was tested using two models of skin inflammation: oxazolone (OX)-induced contact dermatitis in mice and compound 48/80-treated HaCaT cells. As biomarkers of skin inflammation, cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) levels were measured. Results OX-induced contact dermatitis was suppressed markedly in mice that were treated with an ointment containing 5% EPS as evidenced by a decrease in the extent of scaling and thickening (p<0.05) and supported by a histological study. COX-2 (messenger RNA [mRNA] and protein) and NGF (mRNA) levels, which were upregulated in the skin of OX-treated mice, were suppressed markedly in the skin of OX+EPS-treated mice. Consistent with this, compound 48/80-induced expression of COX-2 (mRNA and protein) and NGF (mRNA) in HaCaT cells were suppressed by EPS treatment in a dose-dependent manner. As an inhibitor of NF-κB, IκB protein levels were dose-dependently upregulated by EPS. Fluorescence-activated cell sorting (FACS) analysis revealed that EPS scavenged compound 48/80-induced reactive oxygen species (ROS) in HaCaT cells. Conclusion EPS exerts a potent anti-inflammatory activity via its anti-oxidant activity in both mouse skin and compound 48/80-treated HaCaT cells in vitro. Compound 48/80-treated HaCaT cells are a useful new in vitro model of skin inflammation. PMID:25834352

  16. Comparative anti-inflammatory characterization of wild fruiting body, liquid-state fermentation, and solid-state culture of Taiwanofungus camphoratus in microglia and the mechanism of its action.

    PubMed

    Liu, Der-Zen; Liang, Hong-Jen; Chen, Chien-Ho; Su, Ching-Hua; Lee, Tzong-Huei; Huang, Chun-Ting; Hou, Wen-Chi; Lin, Shyr-Yi; Zhong, Wen-Bin; Lin, Pei-Jung; Hung, Ling-Fang; Liang, Yu-Chih

    2007-08-15

    Taiwanofungus camphoratus (syn. Antrodia camphorata), a medicinal mushroom in Taiwan, is reputed to provide several therapeutic benefits, but the wild fruiting body is very rare. In this study, we used Taiwanofungus camphoratus extracts from wild fruiting bodies and two types of artificial cultivation (solid-state culture and liquid-state fermentation) to examine their anti-inflammatory effects in microglia cells and their possible roles in protection against neurodegenerative diseases. First, EOC13.31 microglia was treated with various kinds of Taiwanofungus camphoratus extracts and lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) to evaluate the iNOS expression. Western blot and RT-PCR analysis showed that among the various kinds of extracts from wild fruiting bodies, methanol extracts were the most potent inhibitors of iNOS expression. Secondly, the potency of methanol extracts could be ranked as follows: extracts of wild fruiting body>solid-state culture>liquid-state fermentation. To clarify the mechanisms involved, methanol extracts from fruiting body were found to inhibit the phosphorylation of extracellular signal-regulated protein kinases (ERK), c-Jun NH2-terminal protein kinases (JNK) and signal transducer and activator of transcription-1 (STAT-1) induced by LPS/IFN-gamma. Methanol extracts from fruiting body also inhibited NF-kappaB activation through the prevention of inhibitor kappaB (IkappaB) degradation. Moreover, methanol extracts from wild fruiting body inhibited both the iNOS and cyclooxygenase-2 (COX-2) expression induced by beta-amyloid in microglia in a dose-dependent manner. In an animal model, we confirmed that methanol extracts from fruiting bodies were able to suppress ear edema, indicating that they have anti-inflammatory activity in vivo. These results suggest that Taiwanofungus camphoratus exhibits an anti-inflammatory activity that might contribute to the prevention of neurodegenerative diseases.

  17. Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis.

    PubMed

    Kanashiro, Alexandre; Sônego, Fabiane; Ferreira, Raphael G; Castanheira, Fernanda V S; Leite, Caio A; Borges, Vanessa F; Nascimento, Daniele C; Cólon, David F; Alves-Filho, José Carlos; Ulloa, Luis; Cunha, Fernando Q

    2017-03-01

    Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases. Interesting studies have dissected the anatomical constituents of the so-called "cholinergic anti-inflammatory pathway", suggesting that electrical vagus nerve stimulation and pharmacological activation of beta-2 adrenergic and alpha-7 nicotinic receptors could be alternative strategies for improving inflammatory conditions. However, the literature on infectious diseases, such as sepsis, is still controversial and, therefore, the real therapeutic potential of this neuroimmune pathway is not well defined. In this review, we will discuss the beneficial and detrimental effects of neural manipulation in sepsis, which depend on the multiple variables of the immune system and the nature of the infection. These observations suggest future critical studies to validate the clinical implications of vagal parasympathetic signaling in sepsis treatment.

  18. Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Retinal Diseases.

    PubMed

    Rodrigues, Eduardo Büchele; Farah, Michel Eid; Bottós, Juliana Mantovani; Bom Aggio, Fabio

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of drugs in medicine and ophthalmology. Several NSAIDs have been commercially available for many years: diclofenac, flurbiprofen, indomethacin, ketorolac and suprofen. The purpose of this chapter is to review the clinical use of earlier and newer pharmacologic agents of the NSAID class. NSAIDs may have a modulating effect on ocular inflammation and pain through the prevention of prostaglandin synthesis via cyclooxygenase inhibition. Newer-generation NSAIDs have emerged in recent years for the treatment of ocular pain and inflammation. Nepafenac ophthalmic suspension 0.1% is a new topical NSAID prodrug that has been approved by the Food and Drug Administration for the treatment of pain and inflammation after cataract surgery. Preliminary data suggest nepafenac may also provide unique efficacy in the posterior segment, since its corneal permeability characteristics are superior to those of other NSAIDs. Nevanac, diclofenac, ketorolac and bromfenac are some notable NSAID candidates which should be investigated intravitreally or topically for retinal pharmacotherapy. In addition, for intraocular surgery, NSAIDs can help to prevent intraoperative miosis, reduce ocular pain, decrease postoperative inflammation and prevent cystoid macular edema. Retinal, choroidal and vitreous diseases may be the target of future nepafenac studies, either as monotherapy or as combination treatments.

  19. Development of Osmotically Controlled Mucoadhesive Cup-Core (OCMC) Tablet for The Anti-Inflammatory Activity.

    PubMed

    Ranchhodbhai Patel, Hitesh; Manordas Patel, Madhabhai

    2010-01-01

    The aim of the present study was to prepare and evaluate an osmotically controlled mucoadhesive cup-core (OCMC) containing aceclofenac. A special technique was used while preparing an OCMC. Stability of OCMC was determined in natural human saliva, and it was found that both pH and device are stable in human saliva. OCMC was evaluated by weight uniformity, thickness, hardness, friability, swelling, mucoadhesive strength and in vitro drug release. Swelling index was higher with formulations containing hydroxypropyl methylcellulose (HPMC) K4M alone, and it decreases with its decreasing concentration in the OCMC. The in vitro drug release studies showed a release with the composition of formulation up to 12 h. The mechanism of drug release was found to be zero order kinetics with diffusion controlled drug release. It has shown significant anti-inflammatory activity (P<0.001) and no hypersensitive reaction. It can be concluded that by changing the content of OCMC system, a desire effect is generated and it overcomes the drawback associated with the conventional buccal adhesive tablet.

  20. Dual effect of nitric oxide donors on cyclooxygenase-2 expression in human mesangial cells.

    PubMed

    Díaz-Cazorla, M; Pérez-Sala, D; Lamas, S

    1999-05-01

    Nitric oxide (NO) is emerging as a key regulator of gene expression, capable of playing either positive or negative roles. The results of this study indicate that NO exerts a dual effect on cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). Treatment of HMC with NO synthase inhibitors attenuated interleukin-1beta (IL-1beta/tumor necrosis factor-alpha (TNF-alpha)-elicited COX-2 protein and mRNA expression, suggesting a positive role of endogenous NO on COX-2 induction. However, NO donors (sodium nitroprusside [SNP] and S-nitroso-N-acetylpenicillamine [SNAP]) amplified cytokine-elicited COX-2 expression at early time points of treatment (up to 8 h for mRNA and up to 24 h for protein expression), but were inhibitory at later times. Oligonucleotide decoy experiments confirmed the importance of nuclear factor kappaB (NF-kappaB) activation for COX-2 induction by IL-1beta/TNF-alpha. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME) did not affect initial activation of NF-kappaB by IL-1beta/TNF-alpha, but unveiled an inhibitory effect of NO generation on NF-kappaB activity after 4 h. In HMC supplemented with SNP, cytokine-induced NF-kappaB activation was potentiated at early times of induction (5 to 15 min), but inhibited at later times (1 to 4 h), suggesting a dual effect of NO donors on NF-kappaB activation. Interestingly, IkappaBalpha protein levels followed a reciprocal pattern of expression: IkappaBalpha levels were lower at early times of induction in NO donor-supplemented cells; however, after 1 h of treatment, IkappaBalpha levels became higher than in cells treated only with cytokines. In the presence of SNP, cytokine-elicited IkappaBalpha mRNA induction was initially delayed, but was amplified at later times. These changes in IkappaBalpha expression could contribute to the dual effects of NO donors on NF-kappaB activation and COX-2 expression in HMC.

  1. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State.

    PubMed

    Koren-Gluzer, Marie; Rosenblat, Mira; Hayek, Tony

    2015-01-01

    Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages' response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages' abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes.

  2. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

    PubMed Central

    Koren-Gluzer, Marie; Rosenblat, Mira; Hayek, Tony

    2015-01-01

    Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages' response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages' abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. PMID:26779262

  3. A novel synthetic isothiocyanate ITC-57 displays antioxidant, anti-inflammatory, and neuroprotective properties in a mouse Parkinson's disease model.

    PubMed

    Lee, Ji Ae; Son, Hyo Jin; Kim, Ji Hyun; Park, Ki Duk; Shin, Nari; Kim, Hye Ri; Kim, Eun Mee; Kim, Dong Jin; Hwang, Onyou

    2016-01-01

    The degenerative process of the nigral dopamine(DA)rgic neurons in Parkinson's disease (PD) involves both oxidative stress and neuroinflammation. In the present study, we aimed at developing a novel antioxidant and anti-inflammatory agent for PD therapy. Toward this end, we screened a novel focused library of isothiocyanate derivatives that we have generated for an anti-inflammatory property. We obtained a novel compound ITC-57 and found that ITC-57 effectively induced gene expression of the antioxidant enzymes NAD(P)H quinone oxidoreductase-1, the catalytic and modulatory subunits of glutamylcysteine ligase, and HO-1 in DAergic neuronal CATH.a cells and protected CATH.a cells from oxidative damages. The compound also induced the same antioxidant enzymes in microglial BV-2 cells and suppressed the production of the proinflammatory molecules nitric oxide, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in lipopolysaccharide-activated BV-2 cells. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-elicited mouse model of PD, ITC-57 protected the DAergic neurons from degeneration, induced HO-1, lowered TNF-α, and suppressed microglial activation in the nigra. Furthermore, ITC-57 prevented the PD-associated motor deficits from occurring. Taken together, ITC-57 would be useful toward development of a disease-modifying therapy for PD.

  4. Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system.

    PubMed

    Esmaeili, Fariba; Rajabnejhad, Saeid; Partoazar, Ali Reza; Mehr, Shahram Ejtemaei; Faridi-Majidi, Reza; Sahebgharani, Mousa; Syedmoradi, Leila; Rajabnejhad, Mohammad Reza; Amani, Amir

    2016-11-01

    Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1%, 2% and 4% of eugenol as well as a nanoemulsion system containing 4% eugenol and 0.5% piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2% eugenol (oil phase), 14% Tween 20 (surfactant) and 14% isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam.

  5. Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents.

    PubMed

    Boukhary, Rima; Raafat, Karim; Ghoneim, Asser I; Aboul-Ela, Maha; El-Lakany, Abdalla

    2016-01-01

    Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti-inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2-diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin-Ciocalteu reagent, and high-performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti-inflammatory activity, carrageenan-induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti-inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti-inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti-inflammatory drugs.

  6. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus.

    PubMed

    Li, Zheng; Geng, Ya-Na; Jiang, Jian-Dong; Kong, Wei-Jia

    2014-01-01

    Oxidative stress and inflammation are proved to be critical for the pathogenesis of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants such as Coptis chinensis and Hydrastis canadensis and with multiple pharmacological activities. Recent studies showed that BBR had antioxidant and anti-inflammatory activities, which contributed in part to its efficacy against diabetes mellitus. In this review, we summarized the antioxidant and anti-inflammatory activities of BBR as well as their molecular basis. The antioxidant and anti-inflammatory activities of BBR were noted with changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR administration in diabetic animals. BBR inhibited oxidative stress and inflammation in a variety of tissues including liver, adipose tissue, kidney and pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR were complex, which involved multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor- κ B (NF- κ B) pathway. Detailed mechanisms and pathways for the antioxidant and anti-inflammatory activities of BBR still need further investigation. Clarification of these issues could help to understand the pharmacology of BBR in the treatment of diabetes mellitus and promote the development of antidiabetic natural products.

  7. Anti-inflammatory mechanism research of tanshinone II A by module-based network analysis.

    PubMed

    Zheng, Shichao; Ren, Zhenzhen; Zhang, Yanling; Qiao, Yanjiang

    2014-01-01

    Tanshinone IIA (Tan IIA) is one of the major fat-soluble ingredients in Salvia miltiorrhiza which has been widely used for various inflammatory conditions associated with cardiovascular and cerebrovascular disorders. However, the underlying anti-inflammatory mechanisms of Tan IIA are incompletely understood. The purpose of this study was to illuminate the anti-inflammatory mechanism of Tan IIA based on the protein interaction network (PIN) analysis. A PIN of Tan IIA was constructed with 281 nodes and 814 interactions and analyzed by gene ontology (GO) enrichment analysis based on Markov Cluster algorithm (MCL). Three modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of Tan IIA may be partly attributable to the mediate activation of TRAF2, TRAF3 and TRAF6, to inhibit the toll-like receptor signaling pathway and combine with AGER. Therefore, the module-based network analysis approach will be a new method for better understanding the anti-inflammatory mechanism of Tan IIA.

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

    PubMed Central

    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. PMID:23861612

  9. Evaluation of anti-inflammatory activity of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae) fruit extract in rats.

    PubMed

    Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

    2013-01-01

    Several species of the family Bromeliaceae are characterized by the production of proteases in unusual amounts, especially in fruits. Bromelain, an extract rich in cysteine endopeptidases obtained from Ananas comosus L., and a few other proteases have been used as anti-inflammatory agents for some years, but bromelain is still mainly being used as alternative and/or complementary therapy to the treatment with glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. In this study, the anti-inflammatory action of a partially purified extract from Pseudananas macrodontes (Morr.) Harms fruits (PPE(Pm)) is presented, whose main components are cysteine endopeptidases. The effect of PPE(Pm) was assessed in carrageenan-induced and serotonin-induced rat paw edema, as well as in the cotton pellet granuloma model. Doses with equal proteolytic activity of PPE(Pm) and bromelain produced significantly similar anti-inflammatory responses in the acute inflammatory models assayed, supporting the hypothesis that proteolytic activity could be responsible for the anti-inflammatory action. On the contrary, comparable anti-inflammatory effects of PPE(Pm) and bromelain in the chronic inflammatory assay required a much lower proteolytic activity content of PPE(Pm), which could be due to a differential affinity for the protein target involved in this process.

  10. Structure–activity relationship of terpenes with anti-inflammatory profile – a systematic review.

    PubMed

    Souza, Marilia Trindade de Santana; Almeida, Jackson Roberto Guedes da Silva; Araujo, Adriano Antunes de Souza; Duarte, Marcelo Cavalcante; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca; dos Santos, Marcio Roberto Viana; Quintans-Júnior, Lucindo José

    2014-09-01

    Inflammation is a complex biological response that in spite of having available treatments, their side effects limit their usefulness. Because of this, natural products have been the subject of incessant studies, among which the class of terpenes stands out. They have been the source of study for the development of anti-inflammatory drugs, once their chemical diversity is well suited to provide skeleton for future anti-inflammatory drugs. This systematic review reports the studies present in the literature that evaluate the anti-inflammatory activity of terpenes suffering any change in their structures, assessing whether these changes also brought changes in their effects. The search terms anti-inflammatory agents, terpenes, and structure–activity relationship were used to retrieve English language articles in SCOPUS, PUBMED and EMBASE published between January 2002 and August 2013. Twenty-seven papers were found concerning the structural modification of terpenes with the evaluation of antiinflammatory activity. The data reviewed here suggest that modified terpenes are an interesting tool for the development of new anti-inflammatory drugs.

  11. Systems Pharmacology Dissection of the Anti-Inflammatory Mechanism for the Medicinal Herb Folium Eriobotryae

    PubMed Central

    Zhang, Jingxiao; Li, Yan; Chen, Su-Shing; Zhang, Lilei; Wang, Jinghui; Yang, Yinfeng; Zhang, Shuwei; Pan, Yanqiu; Wang, Yonghua; Yang, Ling

    2015-01-01

    Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations. PMID:25636035

  12. Synthesis and anti-inflammatory evaluations of β-lapachone derivatives.

    PubMed

    Tseng, Chih-Hua; Cheng, Chih-Mei; Tzeng, Cherng-Chyi; Peng, Shin-I; Yang, Chiao-Li; Chen, Yeh-Long

    2013-01-15

    β-Lapachone (β-LAPA), a natural product from the lapacho tree in South America, is a potential chemotherapeutic agent that exhibit a wide variety of pharmacological effects such as anti-virus, anti-parasitic, anti-cancer, and anti-inflammatory activities. In order to discover novel anti-inflammatory agents, we have synthesized a series of β-LAPA derivatives for evaluation. Among them, 4-(4-methoxyphenoxy)naphthalene-1,2-dione (6b) was found to be able to inhibit NO and TNF-α released in LPS-induced Raw 264.7 cells. Inhibition of iNOS and COX-2 was also observed in compound 6b treated cells. Mechanism studies indicated that 6b exhibited anti-inflammatory properties by suppressing the release of pro-inflammatory factors through down-regulating NF-κB activation. In addition, it suppressed NF-κB translocation by inhibiting the phosphorylation of p38 kinase. Our results also indicate that the inhibitory effect of 6b on LPS-stimulated inflammatory mediator production in Raw 264.7 cell is associated with the suppression of the NF-κB and MAPK signaling pathways. A low cytotoxicity (IC(50) = 31.70 μM) and the potent anti-inflammatory activity exhibited by compound 6b make this compound a potential lead for developing new anti-inflammatory agents. Further structural optimization of compound 6b is on-going.

  13. Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity.

    PubMed

    Franco, Luis A; Ocampo, Yanet C; Gómez, Harold A; De la Puerta, Rocío; Espartero, José L; Ospina, Luis F

    2014-11-01

    Physalis peruviana is a native plant from the South American Andes and is widely used in traditional Colombian medicine of as an anti-inflammatory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Previous studies performed by our group on P. peruviana calyces showed potent anti-inflammatory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the active compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vitro. The enriched fraction of P. peruviana was purified by several chromatographic methods to obtain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were elucidated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using λ-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macrophages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation induced by λ-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demonstrated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. peruviana that showed a potent anti-inflammatory effect. These results suggest the potential of sucrose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases.

  14. Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages.

    PubMed

    Wang, Ji; Kang, Yu-Xia; Pan, Wen; Lei, Wan; Feng, Bin; Wang, Xiao-Juan

    2016-06-20

    Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%-8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

  15. Anti-inflammatory effect of novel andrographolide derivatives through inhibition of NO and PGE2 production.

    PubMed

    Dai, Gui-Fu; Zhao, Jin; Jiang, Zhi-Wen; Zhu, Li-Ping; Xu, Hai-Wei; Ma, Wen-Yan; Chen, Xiao-Rang; Dong, Rui-Jing; Li, Wei-Yi; Liu, Hong-Min

    2011-12-01

    Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2-6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure-activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p<0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti-inflammatory effect against ear edema in mice (79.4%; 1.35 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p<0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE(2) production.

  16. Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species

    PubMed Central

    Amorim, Jorge Luis; Simas, Daniel Luiz Reis; Pinheiro, Mariana Martins Gomes; Moreno, Daniela Sales Alviano; Alviano, Celuta Sales; da Silva, Antonio Jorge Ribeiro

    2016-01-01

    Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia. PMID:27088973

  17. SR-BI mediates high density lipoprotein (HDL)-induced anti-inflammatory effect in macrophages.

    PubMed

    Song, Gyun Jee; Kim, Seong-Min; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-01-30

    High density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediates selective cholesteryl ester uptake from lipoproteins into the liver as well as cholesterol efflux from macrophages to HDL. Recently, strong evidence has demonstrated the anti-inflammatory effect of HDL, although the mechanism of action is not fully understood. In this study, we showed that the anti-inflammatory effects of HDL are dependent on SR-BI expression in THP-1 macrophages. Consistent with earlier findings, pretreatment of macrophages with HDL abolished LPS-induced TNFα production. HDL also inhibited LPS-induced NF-κB activation. In addition, knockdown of SR-BI or inhibition of SR-BI ligand binding abolished the anti-inflammatory effect of HDL. SR-BI is a multi-ligand receptor that binds to modified lipoproteins as well as native HDL. Since modified lipoproteins have pro-inflammatory properties, it is unclear whether SR-BI activated by modified HDL has an anti- or pro-inflammatory effect. Glycated HDL induced NF-κB activation and cytokine production in macrophages in vitro, suggesting a pro-inflammatory effect for modified HDL. Moreover, inhibition of SR-BI function or expression potentiated glycated HDL-induced TNF-α production, suggesting an anti-inflammatory effect for SR-BI. In conclusion, SR-BI plays an important function in regulating HDL-mediated anti-inflammatory response in macrophages.

  18. Anti-inflammatory activity of Urera baccifera (Urticaceae) in Sprague-Dawley rats.

    PubMed

    Badilla, B; Mora, G; Lapa, A J; Emim, J A

    1999-09-01

    On a preliminary test, anti-inflammatory and analgesic dose-related activities on rats were observed for the aqueous fraction of Urera baccifera; this extract was bioassay-guided fractionated and the final aqueous fraction was used according the ethnobotanical use. Carrageenan-induced edema (n = 6), was used as an assay in the fractionating process. The anti-inflammatory and antinociceptive properties of the final aqueous fraction were studied using in vivo models. For the anti-inflammatory activity rat paw edema (n = 6), pleurisy induced by carrageenan (n = 6) and ear edema induced by topical croton oil (n = 6) models were used, and tail-flick test (n = 6), abdominal constrictions induced by acetic acid (n = 6), and formalin test (n = 6), were used for the antinociceptive activity. The tests performed showed an inhibition effect on leukocyte migration, and a reduction on pleural exudate, as well as dose-dependant peripheral analgesic activity, at a range of 25-100 mg/kg i.p. The final aqueous fraction contains most of the anti-inflammatory activity of the plant U. baccifera. A possible mechanism of action is discussed and based on the results we conclude that this plant has a potential for both anti-inflammatory and analgesic activity at the clinical level.

  19. A Systematic Review for Anti-Inflammatory Property of Clusiaceae Family: A Preclinical Approach

    PubMed Central

    de Melo, Mônica Santos; Quintans, Jullyana de Souza Siqueira; Araújo, Adriano Antunes de Souza; Duarte, Marcelo Cavalcante; Bonjardim, Leonardo Rigoldi; Moraes, Valéria Regina de Souza; de Araújo-Júnior, João Xavier

    2014-01-01

    Background. Clusiaceae family (sensu lato) is extensively used in ethnomedicine for treating a number of disease conditions which include cancer, inflammation, and infection. The aim of this review is to report the pharmacological potential of plants of Clusiaceae family with the anti-inflammatory activity in animal experiments. Methods. A systematic review about experiments investigating anti-inflammatory activity of Clusiaceae family was carried out by searching bibliographic databases such as Medline, Scopus and Embase. In this update, the search terms were “anti-inflammatory agents,” “Clusiaceae,” and “animals, laboratory.” Results. A total of 255 publications with plants this family were identified. From the initial 255 studies, a total of 21 studies were selected for the final analysis. Studies with genera Allanblackia, Clusia, Garcinia or Rheedia, and Hypericum showed significant anti-inflammatory activity. The findings include a decrease of total leukocytes, a number of neutrophils, total protein concentration, granuloma formation, and paw or ear edema formation. Other interesting findings included decreased of the MPO activity, and inflammatory mediators such as NF-κB and iNOS expression, PGE2 and Il-1β levels and a decrease in chronic inflammation. Conclusion. The data reported suggests the anti-inflammatory effect potential of Clusiaceae family in animal experiments. PMID:24976853

  20. Propyphenazone-Based Analogues as Prodrugs and Selective Cyclooxygenase-2 Inhibitors

    PubMed Central

    2014-01-01

    Improving the gastrointestinal safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) is an important goal. Herein, we report two strategies, using the nonacidic propyphenazone structure, with potential to overcome the side effects of NSAIDs. Propyphenazone was employed to temporarily mask the free acid group of the widely used NSAIDs ibuprofen, diclofenac, and ketoprofen to develop three mutual prodrugs hypothesized to have minimal GI irritation. The three prodrugs exhibit in vivo anti-inflammatory and analgesic activities with improved potency over each parent drug when compared to a nonhydrolyzable control betahistine–propyphenazone (BET–MP). Additionally, ANT–MP formed by the irreversible coupling of propyphenazone and 4-aminoantipyrine, displayed exceptional COXII selectivity (COXII IC50 of 0.97 ± 0.04 μM, compared to no observed inhibition of COXI at 160 μM). Inhibition of COXII suppresses inflammatory diseases without affecting COXI-mediated GI tract events. ANT–MP exhibited maximal analgesic effect when tested in vivo in an abdominal writhing assay (100% protection) and its anti-inflammatory activity showed a peak at 2 h in a carrageenan-induced paw edema model. Its unique selectivity toward the COXII enzyme was investigated using molecular modeling techniques. PMID:25221653

  1. Regulation of p53, nuclear factor {kappa}B and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin

    SciTech Connect

    Kalra, Neetu; Bhui, Kulpreet; Roy, Preeti; Srivastava, Smita; George, Jasmine; Prasad, Sahdeo; Shukla, Yogeshwer

    2008-01-01

    Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-{kappa}B), we also investigated the effect of bromelain on Cox-2 and NF-{kappa}B expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-{kappa}B by blocking phosphorylation and subsequent degradation of I{kappa}B{alpha}. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition of NF-{kappa}B-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects.

  2. Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin.

    PubMed

    Kalra, Neetu; Bhui, Kulpreet; Roy, Preeti; Srivastava, Smita; George, Jasmine; Prasad, Sahdeo; Shukla, Yogeshwer

    2008-01-01

    Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-kappaB), we also investigated the effect of bromelain on Cox-2 and NF-kappaB expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-kappaB by blocking phosphorylation and subsequent degradation of IkappaBalpha. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition of NF-kappaB-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects.

  3. Salvianolic Acid B Inhibits Growth of Head and Neck Squamous Cell Carcinoma in vitro and in vivo via Cyclooxygenase-2 and Apoptotic Pathways

    PubMed Central

    Hao, Yubin; Xie, Tianpei; Korotcov, Alexandru; Zhou, Yanfei; Pang, Xiaowu; Shan, Liang; Ji, Hongguang; Sridhar, Rajagopalan; Wang, Paul; Califano, Joseph; Gu, Xinbin

    2010-01-01

    Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a non steroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from Salvia miltiorrhiza Bge by solvent extraction followed by two chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC50 of 18 and 50 µM respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80mg/kg/day) or celecoxib (5mg/kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were significantly lower than those in celecoxib treated or untreated control groups (p<0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E2 synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment. PMID:19123475

  4. Effects of nimesulide, acetylsalicylic acid, ibuprofen and nabumetone on cyclooxygenase-1- and cyclooxygenase-2-mediated prostanoid production in healthy volunteers ex vivo.

    PubMed

    Kerola, Markku; Vuolteenaho, Katriina; Kosonen, Outi; Kankaanranta, Hannu; Sarna, Seppo; Moilanen, Eeva

    2009-01-01

    : The beneficial actions of non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with inhibition of cyclooxygenase-2 (COX-2), whereas some of their adverse effects are associated mainly with inhibition of COX-1. Selective COX-2 inhibitors reduce the risk of gastrointestinal adverse events, but increase the risk of thromboembolic events pointing to importance of optimal COX-1/COX-2 inhibition in drug safety. We compared the effects of acetylsalicylic acid, ibuprofen, nabumetone and nimesulide on COX-1 and COX-2 pathways in healthy volunteers in an ex vivo set-up using single oral doses commonly used to treat acute pain. In a randomized, double-blind four-phase cross-over study, 15 healthy volunteers were given orally a single dose of either acetylsalicylic acid 500 mg, ibuprofen 400 mg, nabumetone 1 g or nimesulide 100 mg. Blood samples were drawn before and 1, 3, 6, 24 and 48 hr after the drug for the assessment of COX-1 and COX-2 activity. COX-1 activity was measured as thromboxane(2) production during blood clotting and COX-2 activity as endotoxin-induced prostaglandin E(2) synthesis in blood leucocytes. The data show that after a single oral dose these four NSAIDs have different profiles of action on COX-1 and COX-2. As expected, acetylsalicylic acid appeared to be COX-1-selective and ibuprofen effectively inhibited both COX-1 and COX-2. Nabumetone showed only a slight inhibitory effect on COX-1 and COX-2. Nimesulide caused almost complete suppression of COX-2 activity and a partial reduction of COX-1 activity. This confirms the relative COX-2 selectivity of nimesulide.

  5. Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid

    SciTech Connect

    Huang, Bor-Ren; Tsai, Cheng-Fang; Lin, Hsiao-Yun; Tseng, Wen-Pei; Huang, Shiang-Suo; Wu, Chi-Rei; Lin, Chingju; Yeh, Wei-Lan; Lu, Dah-Yuu

    2013-05-15

    We investigated the interaction between proinflammatory and inflammatory responses caused by Staphylococcus aureus-derived lipoteichoic acid (LTA) in primary cultured microglial cells and BV-2 microglia. LTA induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels increase in a concentration- and time-dependent manner. Meanwhile, LTA also increased nitric oxide (NO) and PGE{sub 2} production in microglia. Administration of TLR2 antagonist effectively inhibited LTA-induced NO, iNOS, and COX-2 expression. Moreover, treatment of cells with LTA caused a time-dependent activation of ERK, p38, JNK, as well as AKT. We also found that LTA-induced iNOS and COX-2 up-regulation were attenuated by p38, JNK, and PI3-kinase inhibitors. On the other hand, LTA-enhanced HO-1 expression was attenuated by p38 and PI3-kinase inhibitors. Treatment of cells with NF-κB and AP-1 inhibitors antagonized LTA-induced iNOS and COX-2 expression. However, only NF-κB inhibitors reduced LTA-induced HO-1 expression in microglia. Furthermore, stimulation of cells with LTA also activated IκBα phosphorylation, p65 phosphorylation at Ser{sup 536}, and c-Jun phosphorylation. Moreover, LTA-induced increases of κB-DNA and AP-1-DNA binding activity were inhibited by p38, JNK, and PI3-kinase inhibitors. HO-1 activator CoPP IX dramatically reversed LTA-induced iNOS expression. Our results provided mechanisms linking LTA and inflammation/anti-inflammation, and indicated that LTA plays a regulatory role in microglia activation. - Highlights: • LTA causes an increase in iNOS, COX-2, and HO-1 expression in microglia. • LTA induces iNOS and COX-2 expression through TLR-2/NF-κB and AP-1 pathways. • HO-1 expression is regulated through p38, JNK, PI3K/AKT and AP-1 pathways. • Induced HO-1 reduces LTA-induced iNOS expression. • LTA plays a regulatory role on inflammatory/anti-inflammatory responses.

  6. In vitro anti-inflammatory activity of phenolic rich extracts from white and red common beans.

    PubMed

    García-Lafuente, Ana; Moro, Carlos; Manchón, Noelia; Gonzalo-Ruiz, Alicia; Villares, Ana; Guillamón, Eva; Rostagno, Mauricio; Mateo-Vivaracho, Laura

    2014-10-15

    According to epidemiological evidence, diets rich in fruits and vegetables can reduce the incidence of several chronic diseases that share an inflammatory component. These protective effects are attributed, in part, to the occurrence of different antioxidant components, mainly phenolic compounds. Our aim was to characterise phenolic composition, and to determine antioxidant and anti-inflammatory activities of phenolic rich extracts obtained from two kinds of common beans, white kidney beans (WKB) and round purple beans (RPB). Phenolic acids were the predominant component in WKB extracts, whereas RPB extracts presented higher concentrations of phenolic compounds, mainly catechin derivatives, proanthocyanidins and catechin glucoside. In addition, RPB extracts showed higher antioxidant capacity and higher anti-inflammatory activity by the reduction of NO production and cytokine mRNA expression of LPS stimulated macrophages. These results suggest that common bean extracts may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

  7. Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

    PubMed Central

    Steel, Helen C.; Theron, Annette J.; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

    2012-01-01

    Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance. PMID:22778497

  8. Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

    PubMed Central

    Lee, Young-Sun; Jun, Hee-Sook

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammation in vivo and in vitro, and their molecular mechanisms of anti-inflammatory action. PMID:27110066

  9. Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases.

    PubMed

    Scott, David A; Martin, Michael

    2006-12-14

    Discoveries in the first few years of the 21st century have led to an understanding of important interactions between the nervous system and the inflammatory response at the molecular level, most notably the acetylcholine (ACh)-triggered, alpha7-nicotinic acetylcholine receptor (alpha7nAChR)-dependent nicotinic anti-inflammatory pathway. Studies using the alpha7nAChR agonist, nicotine, for the treatment of mucosal inflammation have been undertaken but the efficacy of nicotine as a treatment for inflammatory bowel diseases remains debatable. Further understanding of the nicotinic anti-inflammatory pathway and other endogenous anti-inflammatory mechanisms is required in order to develop refined and specific therapeutic strategies for the treatment of a number of inflammatory diseases and conditions, including periodontitis, psoriasis, sarcoidosis, and ulcerative colitis.

  10. Anti-inflammatory properties of new bioisosteres of indomethacin synthesized from safrole which are sulindac analogues.

    PubMed

    Pereira, E F; Pereira, N A; Lima, M E; Coelho, F A; Barreiro, E J

    1989-01-01

    The anti-inflammatory activities of new compounds (I, II, III and IV) synthesized in 30% overall yield from the abundant natural product safrole, the principal chemical constituent of the oil of sassafras (Ocotea pretiosa, Lauraceae), were determined in mice. The synthesis of these new indenyl-acetic acids (I and II) and indenyl-propionic acids (III and IV) was based on the minimal structural features of non-steroid anti-inflammatory agents of the aryl- or heteroarylcarboxylic acid group. The compounds exhibited potencies 4- to 10-fold less than that of indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all the new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. The results confirm the anticipated bioisosteric relationship between these synthetic derivatives, designed as sulindac analogues, and the classical non-steroidal anti-inflammatory agent, indomethacin.

  11. Mushrooms: A Potential Natural Source of Anti-Inflammatory Compounds for Medical Applications

    PubMed Central

    Elsayed, Elsayed A.; El Enshasy, Hesham; Wadaan, Mohammad A. M.; Aziz, Ramlan

    2014-01-01

    For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents. PMID:25505823

  12. Analgesic and Anti-inflammatory action of Opuntia elatior Mill fruits

    PubMed Central

    Chauhan, Sanjay P.; Sheth, Navin R.; Suhagia, Bhanubhai N.

    2015-01-01

    Background: Opuntia elatio Mill is a xerophytic plant with potentially active nutrients. It is traditionally appreciated for its pharmacological properties; however, the scientific information on this plant is insufficient. Objective: The present study evaluates the antinociceptive and anti-inflammatory action of prickly pear. Materials and Methods: Writhing and tail-immersion tests were carried out to evaluate analgesic action, while the carrageenan-induced paw edema and neutrophil adhesion tests were conducted in Albino wistar rats to assess anti-inflammatory action. Results: ED50 values of the fruit juice in writhing, tail immersion, and paw edema test were 0.919, 2.77, and 9.282 ml/kg, respectively. The fruits of Opuntia produced analgesic and anti-inflammatory action in a dose-dependent manner. Conclusion: The results establish the folklore use of prickly pear may be due to the presence of betacyanin and/or other phenolic compounds. PMID:26166996

  13. Nonsteroidal anti-inflammatory drug administration in children with history of wheeze

    PubMed Central

    Sih, Kendra; Goldman, Ran D.

    2016-01-01

    Question A child in my clinic who recently sprained his ankle is experiencing pain and having trouble bearing weight on the affected leg. His mother has been giving him acetaminophen, as she was told never to use nonsteroidal anti-inflammatory drugs (NSAIDs) because of his pharmacologically controlled asthma. Is asthma in children a contraindication to giving NSAIDs? Is NSAID-exacerbated respiratory disease (NERD) a real entity? Answer Nonsteroidal anti-inflammatory drugs are effective analgesic and antipyretic medications. While described in adults with some predisposing conditions, NERD has not been clearly described in a large number of children. Nonsteroidal anti-inflammatory drugs can be recommended to children with known wheeze who do not have a history of NERD reaction. PMID:27521389

  14. 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.

  15. The effects of anti-inflammatory agents on skin tumor initiation and aryl hydrocarbon hydroxylase.

    PubMed

    Slaga, T J; Viaje, A; Bracken, W

    1977-02-01

    The effects of various clinically used anti-inflammatory agents on mouse skin tumorigenesis and aryl hydrocarbon hydroxylase (AHH) were investigated. Oxyphenbutazone, a nonsteroidal anti-inflammatory agent, inhibited 3-methylcholanthrene (MC) tumor initiation but was less effective than the steroidal anti-inflammatory agent, dexamethasone. Oxyphenbutazone was not found to induce AHH activity in mouse epidermis, whereas indomethacin and Seclazone had a slight inducing effect. When these agents were added directly to the in vitro AHH assay, they did not inhibit AHH activity. However, additional experiments have shown a decreased epidermally mediated covalent binding of MC to DNA in vitro when the epidermal homogenates were isolated from mice pretreated with either dexamethasone or oxyphenbutazone and MC at 3 or 12 hr before killing.

  16. Phytochemical analysis, antioxidant and anti-inflammatory activity of calyces from Physalis peruviana.

    PubMed

    Toro, Reina M; Aragón, Diana M; Ospina, Luis F; Ramos, Freddy A; Castellanos, Leonardo

    2014-11-01

    Physalis peruviana calyces are used extensively in folk medicine. The crude ethanolic extract and some fractions of calyces were evaluated in order to explore antioxidant and anti-inflammatory activities. The anti-inflammatory activity was evaluated by the TPA-induced ear edema model. The antioxidant in vitro activity was measured by means of the superoxide and nitric oxide scavenging activity of the extracts and fractions. The butanolic fraction was found to be promising due to its anti-inflammatory and antioxidant activities. Therefore, a bio-assay guided approach was employed to isolate and identify rutin (1) and nicotoflorin (2) from their NMR spectroscopic and MS data. The identification of rutin in calyces of P. peruviana supports the possible use of this waste material for phytotherapeutic, nutraceutical and cosmetic preparations.

  17. The multifunctional anti-inflammatory drugs used in the therapy of Alzheimer's disease.

    PubMed

    Shi, S; Wang, Z; Qiao, Z

    2013-01-01

    Inflammation has recently been implicated as a critical mechanism in Alzheimer's disease (AD). Microglia are the resident immune cells in the central nervous system (CNS), and they mediate the inflammatory response in the AD brain. Thus, suppression of microglial activation and subsequent neuroinflammation may be a potential therapeutic approach against AD. In the following review, we briefly discuss the limitations and advantages of current drug targets for AD and then summarize several anti-inflammatory drugs in trial, including natural nonsteroidal anti-inflammatory drugs (NSAIDs), polyphenols and new drugs synthesized based on multi-target directed ligand (MTDL) design. In addition to their anti-inflammatory effects, these drugs can act as anti-oxidants and reduce microglial activation or amyloid-β (Aβ) plaques. Thus, the studies focused on multiple factors in AD processes might reveal the best potential treatment strategy for the future.

  18. Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

    PubMed Central

    Kim, Wan-Su; Choi, Woo Jin; Lee, Sunwoo; Kim, Woo Joong; Lee, Dong Chae; Sohn, Uy Dong; Shin, Hyoung-Shik

    2015-01-01

    The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory cytokine (IL-1β , IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0±3.2%), similar to α-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases. PMID:25605993

  19. Benzophenone-N-ethyl piperidine ether analogues--synthesis and efficacy as anti-inflammatory agent.

    PubMed

    Khanum, Shaukath A; Girish, V; Suparshwa, S S; Khanum, Noor Fatima

    2009-04-01

    A sequence of substituted benzophenone-N-ethyl piperidine ether analogues has been synthesized and evaluated as orally active anti-inflammatory agents with reduced side effects. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin, and phenylbutazone. These analogues showed an interesting anti-inflammatory activity in carrageenan-induced foot pad edema assay. In the air-pouch test, some of the analogues reduced the total number of leukocytes of the exudate, which indicates inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, in the liver and stomach. None of the compounds illustrated significant side effects compared with standard drugs like indomethacin and naproxen.

  20. Chromones: A Promising Ring System for New Anti-inflammatory Drugs.

    PubMed

    Silva, Carlos F M; Pinto, Diana C G A; Silva, Artur M S

    2016-10-19

    The quest for safer anti-inflammatory drugs is still the focus of several medicinal chemistry programs. Chromones (4H-chromen-4-ones) are a group of naturally occurring compounds ubiquitous in plants, and the chromone core has proven to be a privileged scaffold in medicinal chemistry. Herein we provide an overview of the relevance of chromones as anti-inflammatory agents, specifically as inhibitors of cyclooxygenase (COX), 5-lipoxygenase (5-LOX), interleukin-5 (IL-5), and nitric oxide ((.) NO) production. Numerous structure-activity relationships and mechanisms of action are discussed. This review is therefore intended to provide a foundation for the design and synthesis of novel chromone-based compound libraries for further development into safer and more efficient anti-inflammatory agents.

  1. Anti-inflammatory, analgesic and antipyretic activities of Physalis minima Linn.

    PubMed

    Khan, Murad Ali; Khan, Haroon; Khan, Sarwar; Mahmood, Tahira; Khan, Pir Mohammad; Jabar, Abdul

    2009-06-01

    In our present investigation, the crude methanol extract and chloroform fraction of the whole plant of Physalis minima Linn (Solanaceae) was investigated for anti-inflammatory, analgesic and antipyretic activities in NMRI mice and Wistar rats of either sex at 200 and 400 mg/kg, respectively. Various established in-vivo model's were used during the study. Both crude extract and chloroform fraction showed marked anti-inflammatory and analgesic activities as compared to a control at tested doses. The antipyretic potential of the crude extract and chloroform were insignificant in the Brewer's yeast fever model. Therefore, the whole plant of Physalis minima Linn could be considered as a potential candidate for bioactivity-guided isolation of natural anti-inflammatory and analgesic agents.

  2. Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta-caryophyllene.

    PubMed

    Tambe, Y; Tsujiuchi, H; Honda, G; Ikeshiro, Y; Tanaka, S

    1996-10-01

    The gastric cytoprotective effect of beta-caryophyllene, an anti-inflammatory sesquiterpene, was investigated in rats. The oral administration of beta-caryophyllene to rats significantly inhibited gastric mucosal injuries induced by necrotizing agents such as absolute ethanol and 0.6 N HCl, although it failed to prevent water immersion stress- and indomethacin-induced gastric lesions. In addition, this compound hardly affected the secretion of gastric acid and pepsin. Thus, beta-caryophyllene elicited anti-inflammatory effects without any indication of gastric mucosal damage typical of non-steroidal anti-inflammatory agents. Furthermore, this compound manifested cytoprotective effects, rendering the two-dimensional efficacious beta-caryophyllene to be a clinically safe and potentially useful agent.

  3. Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden).

    PubMed

    Toker, Gülnur; Küpeli, Esra; Memisoğlu, Merve; Yesilada, Erdem

    2004-12-01

    Silver linden, Tilia argentea Desf. ex DC (Tiliaceae) leaves are used in the treatment of common cold and bronchitis. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the two main flavonoid glycosides: kaempferol-3,7-O-alpha-dirhamnoside and quercetin-3,7-O-alpha-dirhamnoside isolated from the leaves, were investigated. For the antinociceptive activity, p-benzoquinone-induced writhing test and for the anti-inflammatory activity, carrageenan-induced hind paw edema model in mice were used. Both compounds were shown to possess potent antinociceptive and anti-inflammatory activity at 50 mg/kg dose, per os, without inducing any apparent acute toxicity as well as gastric damage.

  4. Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Tziona, Paraskevi; Kourounakis, Panos N; Rekka, Eleni A

    2015-11-15

    Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders.

  5. Variation in antibacterial and anti-inflammatory activity of different growth forms of Malva parviflora and evidence for synergism of the anti-inflammatory compounds.

    PubMed

    Shale, T L; Stirk, W A; van Staden, J

    2005-01-04

    Malva parviflora leaves and roots were collected from five sites within the Qacha's Nek District in Lesotho. These plants had two distinct growth forms--upright and prostrate. Hexane, methanol and water extracts were made from the plant material and tested for antibacterial and anti-inflammatory activity using the disc diffusion and cyclooxygenase-1 (Cox-1) bioassays, respectively. Hexane, methanol and water extracts made from Malva parviflora with a prostrate growth form inhibited the growth of Gram-positive and Gram-negative bacteria, while extracts made from plants with an upright growth form inhibited the growth of Gram-positive bacteria only. Cox-1 anti-inflammatory activity of hexane, methanol and water extracts did not show any variation between the two growth forms. The hexane extracts of both the leaves and roots were the most inhibitory. The water extracts had the least inhibitory activity. Bioassay-guided fractionation of the root dichloromethane extract showed that Cox-1 anti-inflammatory activity was caused by at least two compounds that acted synergistically to produce the biological effect.

  6. Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities.

    PubMed

    Del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G; LeBlanc, Jean Guy

    2014-02-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory

  7. Antimicrobial, Anti-inflammatory and Antioxidant Activities of Jatropha multifida L. (Euphorbiaceae)

    PubMed Central

    Anani, Kokou; Adjrah, Yao; Améyapoh, Yaovi; Karou, Simplice Damintoti; Agbonon, Amegnona; de Souza, Comlan; Gbeassor, Messanvi

    2016-01-01

    Background: Jatropha multifida is used in Togolease folk medicine for the healing of chronic wounds. Objective: This study aims to investigate antibacterial, anti-inflammatory and antioxidant activities of the leaves ethanolic extract. Materials and Methods: The antimicrobial activity was assayed by National Committee for Clinical Laboratory Standards broth microdilution method on strains of Staphylococcus aureus and Pseudomoas aeruginosa isolated from wounds, whereas the anti-inflammatory activity was performed by carrageenan and histamine induced paw edema method in rat modele. The 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) were used for the antioxidant activity. Results: The antibacterial assay showed an in vitro growth inhibition of P. aeruginosa and S. aureus in dose-dependent manner, with minimum inhibitory concentration values ranging from 2.5 to 3.12 mg/mL for S. aureus and from 6.25 to 12.5 mg/mL for P. aeruginosa. The maximum paw anti-inflammatory effect occurred after 3 and 5 h administration of histamine and carrageenan, respectively. The DPPH radical scavenging and the FRAP assays yielded weak antioxidant activity. Conclusion: J. multifida possesses antibacterial and anti-inflammatory activities that could justify the use of the plant for the treatment of wounds in the folk medicine. SUMMARY Antibacterial on germs isolated from wound, anti-inflammatory and antioxidant activities of Jatropha multifida were assayed by NCCLS broth method, carrageenan and histamine, DPPH and FRAP respectively. The results indicated that Jatropha multifida possesses antibacterial and anti-inflammatory and weak antioxidant activities that could justify its use for the treatment of wounds in the folk medicine. PMID:27034606

  8. Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

    PubMed Central

    del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2014-01-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory

  9. QSAR and Docking Studies on Capsazepine Derivatives for Immunomodulatory and Anti-Inflammatory Activity

    PubMed Central

    Shukla, Aparna; Sharma, Pooja; Prakash, Om; Singh, Monika; Kalani, Komal; Khan, Feroz; Bawankule, Dnyaneshwar Umrao; Luqman, Suaib; Srivastava, Santosh Kumar

    2014-01-01

    Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR) model against target tumor necrosis factor-α (TNF-α) was developed using multiple linear regression method (MLR) with good internal prediction (r2 = 0.8779) and external prediction (r2pred = 0.5865) using Discovery Studio v3.5 (Accelrys, USA). The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS) induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-α. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug. PMID:25003344

  10. Atomic force microscopy based investigations of anti-inflammatory effects in lipopolysaccharide-stimulated macrophages.

    PubMed

    Pi, Jiang; Cai, Huaihong; Yang, Fen; Jin, Hua; Liu, Jianxin; Yang, Peihui; Cai, Jiye

    2016-01-01

    A new method based on atomic force microscopy (AFM) was developed to investigate the anti-inflammatory effects of drugs on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The LPS-stimulated RAW264.7 macrophage cell line is a widely used in vitro cell model for the screening of anti-inflammatory drugs or the study of anti-inflammatory mechanisms. In this work, the inhibitory effects of dexamethasone and quercetin on LPS-CD14 receptor binding in RAW264.7 macrophages was probed by LPS-functionalized tips for the first time. Both dexamethasone and quercetin were found to inhibit LPS-induced NO production, iNOS expression, IκBα phosphorylation, and IKKα/β phosphorylation in RAW264.7 macrophages. The morphology and ultrastructure of RAW264.7 macrophages were determined by AFM, which indicated that dexamethasone and quercetin could inhibit LPS-induced cell surface particle size and roughness increase in RAW264.7 macrophages. The binding of LPS and its receptor in RAW264.7 macrophages was determined by LPS-functionalized AFM tips, which demonstrated that the binding force and binding probability between LPS and CD14 receptor on the surface of RAW264.7 macrophages were also inhibited by dexamethasone or quercetin treatment. The obtained results imply that AFM, which is very useful for the investigation of potential targets for anti-inflammatory drugs on native macrophages and the enhancement of our understanding of the anti-inflammatory