title: Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.
abstract: Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Huang
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Lu
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Hong-Gui
authors.initials: HG
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Geng
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Ping-Hua
authors.initials: PH
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Jinan University , Guangzhou 510632, P. R. China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D036561:Cajanus / Q000737:chemistry*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D012459:Salicylates / Q000737:chemistry* / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D015027:Zebrafish
chemical_list: C549543:3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D010936:Plant Extracts; D012459:Salicylates; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases
keywords: MAPK; NF-κB; PPARγ; anti-inflammation; cajaninstilbene acid