Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation
Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation
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汉黄芩苷通过抑制 NF-kappa B 和 NLRP3 炎性体激活来预防葡聚糖硫酸钠诱导的小鼠实验性结肠炎
DOI：
10.1016/j.bcp.2015.02.002
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发表时间：
2015-03-15
影响因子：
5.8
通讯作者：
Lu, Na
中科院分区：
文献类型：
--
作者：
Sun, Yang;Zhao, Yue;Lu, Na
Previous studies have demonstrated that wogonoside, the glucuronide metabolite of wogonin, has anti-inflammatory, anti-angiogenic and anticancer effects. However, the anti-inflammatory mechanism of wogonoside has not been fully elucidated. Recently, NLRP3 inflammasome has been reported to be correlated with inflammatory bowel disease for its ability to induce IL-1 beta release. Nevertheless, there are few drug candidates targeting NLRP3 inflammasome for this disease. In this study, we investigated the anti-inflammatory effect of wogonoside in dextran sulfate sodium (DSS)-induced murine colitis and further revealed the underlying mechanisms by targeting NF-kappa B and NLRP3 inflammasome. Wogonoside treatment dose-dependently attenuated DSS-induced body weight loss and colon length shortening. Moreover, wogonoside prevented DSS-induced colonic pathological damage, remarkably inhibited inflammatory cells infiltration and significantly decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities. The production of pro-inflammatory mediators in serum and colon was also significantly reduced by wogonoside. The underlying mechanisms for the protective effect of wogonoside in DSS-induced colitis may be attributed to its inhibition on NF-kappa B and NLRP3 inflammasome activation in colons. Furthermore, wogonoside markedly decreased production of IL-1 beta, TNF-alpha and IL-6 and suppressed mRNA expression of pro-IL-1 beta and NLRP3 in phorbol myristate acetate (PMA)-differentiated monocytic THP-1 cells via inhibiting the activation of NF-kappa B and NLRP3 inflammasome. In conclusion, our study demonstrated that wogonoside may exert its anti-inflammatory effect via dual inhibition of NF-kappa B and NLRP3 inflammasome, suggesting that wogonoside might be a potential effective drug for inflammatory bowel diseases. (C) 2015 Elsevier Inc. All rights reserved.
