Wencheng Wei, Lei Wang, Kai Zhou
2017
Citations
0
Influential Citations
19
Citations
Quality indicators
Journal
International Immunopharmacology
Abstract
Abstract Rhapontin (3, 3′, 5‐trihydroxy‐4′‐methoxystilbene‐3‐O‐glucoside) has anti‐thrombotic, anti‐allergic and anti‐diabetic activities. This study aimed to assess the protective effects of rhapontin on intestinal damage in vivo and in vitro. In a dextran sodium sulfate (DSS)‐induced mouse model, oral administration of rhapontin (100 mg/kg) significantly attenuated colonic pathological damage and remarkably inhibited infiltration by inflammatory cells, myeloperoxidase (MPO) activity, NLRP3 inflammasome activation and SIRT1 expression in the colon. Moreover, rhapontin prevented DSS‐induced impairment in the colon epithelium barrier by increasing the expression of tight junction proteins, such as zonula occludens‐1(ZO‐1) and occludin, and reduced apoptosis‐associated protein (cyt‐c, the ratio of bcl‐2/bax and cleaved‐capase9) expression in the colon. The in vitro results showed that rhapontin significantly reduced NLRP3 inflammasome activation and cleaved caspase‐1 expression as well as lowered IL‐1&bgr; secretion in LPS‐stimulated human‐THP‐1‐derived macrophages. Further study revealed that compound EX257 (an SIRT1 inhibitor) blocked the inhibitory effects of rhapontin on NLRP3‐dependent caspase‐1 activation and IL‐&bgr; production in activated macrophages. In addition, in TNF‐&agr;‐stimulated intestinal epithelial NCM460 cells, rhapontin significantly increased the expressions of occludin and ZO‐1 and notably reduced the ratio of bcl‐2/bax and cleaved‐capase9 expression through SRIT1 signaling. In sum, the protective effect of rhapontin is from blocking the NLRP3 priming cascade reaction and is dependent on SIRT1 activation. Our findings demonstrate that rhapontin might be a potential agent for the treatment of colitis by targeting SIRT1. Graphical abstract Figure. No Caption available. HighlightsRhapontin obviously improved the dextran sodium sulfate (DSS) ‐induced colitis in mice.Rhapontin inhibited the DSS‐induced inflammation by reducing NLRP3 activation.Rhapontin clearly prevented DSS‐induced impairment in colon epithelium barrier.Rhapontin might be a potential agent for the treatment of colitis by targeting SIRT1.