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参苓白术散通过抑制半胱天冬酶-1/半胱天冬酶-11介导的细胞焦亡改善葡聚糖硫酸钠诱导的结肠炎。

Shen-Ling-Bai-Zhu-San Improves Dextran Sodium Sulfate-Induced Colitis by Inhibiting Caspase-1/Caspase-11-Mediated Pyroptosis.

作者信息

Chao Limin, Li Zengquan, Zhou Jiahao, Chen Wenqian, Li Yuefei, Lv Weijie, Guo Ao, Qu Qian, Guo Shining

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

出版信息

Front Pharmacol. 2020 May 29;11:814. doi: 10.3389/fphar.2020.00814. eCollection 2020.

Abstract

The traditional Chinese medicine Shen-ling-bai-zhu-san (SLBZS) is described in "Tai Ping Hui Min He Ji Ju Fang." SLBZS has been shown to be effective against many gastrointestinal diseases. The present study aimed to investigate the effect of SLBZS on experimental colitis in mice and to define the potential mechanisms. Our data suggest that compared to the model group, SLBZS treatment increases mouse body weight and colon length, decreases the DAI score, and improves colonic injury. SLBZS reduces the production of cytokines (IL-1β, IL-18, and TNF-α) in colon tissue and mouse colonic mucosal epithelial (MCME) cells. Mechanistically, SLBZS inhibits inflammation by inhibiting the MAPK and NF-κB signaling pathways. Further mechanistic analyses showed that SLBZS attenuates the expression levels of pyroptosis-related genes, including NLRP3, ASC, and GSDMD-N in the colons of mice. In addition, SLBZS restores the levels of the colon tight junction proteins ZO-1 and occludin, suggesting that it protects colonic barrier integrity and ameliorates the progression of colitis. In this paper, we demonstrate that SLBZS attenuates DSS-induced ulcerative colitis injury in mice the MAPK/NF-κB and pyroptosis signaling pathway. These results indicate that SLBZS is a potential drug for the treatment of UC.

摘要

中药参苓白术散(SLBZS)记载于《太平惠民和剂局方》。研究表明,参苓白术散对多种胃肠道疾病有效。本研究旨在探讨参苓白术散对小鼠实验性结肠炎的影响,并明确其潜在机制。我们的数据表明,与模型组相比,参苓白术散治疗可增加小鼠体重和结肠长度,降低疾病活动指数(DAI)评分,并改善结肠损伤。参苓白术散可减少结肠组织和小鼠结肠黏膜上皮(MCME)细胞中细胞因子(IL-1β、IL-18和TNF-α)的产生。机制上,参苓白术散通过抑制丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路来抑制炎症。进一步的机制分析表明,参苓白术散可降低小鼠结肠中焦亡相关基因(包括NLRP3、凋亡相关斑点样蛋白(ASC)和Gasdermin D-N端(GSDMD-N))的表达水平。此外,参苓白术散可恢复结肠紧密连接蛋白闭合蛋白(occludin)和闭锁小带蛋白1(ZO-1)的水平,表明其可保护结肠屏障完整性并改善结肠炎的进展。在本文中,我们证明参苓白术散可减轻二硝基水杨酸(DSS)诱导的小鼠溃疡性结肠炎损伤,其作用机制与MAPK/NF-κB和焦亡信号通路有关。这些结果表明,参苓白术散是一种治疗溃疡性结肠炎(UC)的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f6a/7273825/6b3d0041d4a8/fphar-11-00814-g001.jpg

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