脂多糖
一氧化氮合酶
化学
炎症
激酶
没食子酸表没食子酸酯
没食子酸甲酯
药理学
细胞毒性
多酚
生物
p38丝裂原活化蛋白激酶
生物化学
MAPK/ERK通路
肿瘤坏死因子α
一氧化氮
信号转导
体外
酶
没食子酸
免疫学
抗氧化剂
内分泌学
作者
Ping Huang,Jingxia Hong,Jie Mi,Bolun Sun,Jinjie Zhang,Chao Li,Wenge Yang
标识
DOI:10.1016/j.jep.2021.114897
摘要
Enteromorpha has long been recorded in traditional Chinese medicine, with cholesterol-lowering, anti-cancer, anti-inflammatory and antibacterial effects. Recently, we extracted the polyphenol-enriched fraction from Enteromorpha clathrata (E. clathrata) by ethyl acetate (ECPs), and isolated six individual polyphenols from ECPs via high-speed counter-current chromatography (HSCCC) with high-performance liquid chromatography (HPLC).In this study, we explored the anti-inflammatory activity and underlying mechanism of ECPs in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages.ECPs and the six polyphenols were used for nitric oxide (NO) assay to identify the components with potent inflammation inhibitory effect. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qPCR), flow cytometry, and Western blot analysis were applied to further investigate their anti-inflammatory effects and underlying mechanism in LPS-stimulated RAW264.7 cells.ECPs and the three individual polyphenols, including (-)-epicatechin, epigallocatechin-3-O-gallate and (-)-epicatechin-3-O-gallate, showed in vitro immunosuppressive activity by altering the cell biology at the gene, protein and functional levels in a dose- and species-dependent manner. Their anti-inflammatory effects were achieved by inhibiting LPS-induced production of nitric oxide and its upstream enzyme inducible nitric oxide synthase (iNOS), the pro-inflammatory cytokines including interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), as well as the phagocytotic capacity, without cytotoxicity. The mechanism study further revealed that these anti-inflammatory properties were, at least partly, attributed to the suppressed activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways.These findings indicated for the first time the correlation between the anti-inflammatory activity of ECPs and NF-κB and MAPK signaling pathways, suggesting that polyphenol-enriched organic fraction of E. clathrata could be potential candidate as therapeutic agent for treating inflammatory diseases.
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