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Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives

Author:
Huang, Mei-Yan, Lin, Jing, Lu, Kuo, Xu, Hong-Gui, Geng, Zhi-Zhong, Sun, Ping-Hua, Chen, Wei-Min
Source:
Journal of agricultural and food chemistry 2016 v.64 no.14 pp. 2893-2900
ISSN:
0021-8561
Subject:
Danio rerio, anti-inflammatory activity, fluorescent proteins, image analysis, interleukin-6, larvae, leaves, lipopolysaccharides, macrophages, messenger RNA, mice, mitogen-activated protein kinase, models, neutrophils, nitric oxide, peroxisome proliferator-activated receptors, phosphorylation, pigeon peas, reverse transcriptase polymerase chain reaction, transcription factor NF-kappa B, tumor necrosis factor-alpha
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.
Agid:
5224317