Peimisine ameliorates DSS-induced colitis by suppressing Jak-Stat activation and alleviating gut microbiota dysbiosis in mice

文献类型： 外文期刊

第一作者： Li, Yue

作者： Li, Yue;Han, Jicheng;Bai, Bing;Li, Shanzhi;Xiu, Zhiru;Zhu, Guangze;Jin, Ningyi;Fang, Jinbo;Li, Yiquan;Li, Xiao;Zhu, Yilong;Yang, Xia;Li, Yaru;Shang, Chao;Liu, Zirui;Ge, Chenchen;Jin, Ningyi;Li, Xiao

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关键词： peimisine; Jak-Stat pathway; Th17/Treg cell balance; gut microbiota; inflammatory cytokines; macrophage M1 polarization

期刊名称：JOURNAL OF PHARMACY AND PHARMACOLOGY （ 影响因子：3.3； 五年影响因子：3.7 ）

ISSN： 0022-3573

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Objectives Inflammatory cytokine secretion and gut microbiota dysbiosis play crucial roles in ulcerative colitis. In this research, the protective effects of peimisine on colitis mice were investigated.Methods The protective effects were evaluated by the disease activity index, colonic length, hematoxylin-eosin, and AB/PAS Staining. The protective mechanisms were analyzed by ELISA, Western-blot, immunohistochemistry staining, immunofluorescence staining, and 16S rRNA gene analysis.Key findings The results showed that peimisine treatment could reduce the disease activity index, prevent colonic shortening, and alleviate colon tissue damage. Peimisine treatment also decreased the levels of MCP-1, IL-1 beta, IL-6, IFN-gamma, TNF-alpha and affected macrophage polarization and Th17/Treg cell balance by downregulating the expression of jak1/2, p-jak1/2, stat1/3, and p-stat1/3. Moreover, peimisine treatment significantly increased the abundances of beneficial microbes (e.g. Ruminococcaceae UCG-014 and Lachnospiraceae_NK4A136_group) and decreased the abundances of harmful microbes (e.g. Bacteroides and Escherichia).Conclusions Peimisine can ameliorate colitis by inhibiting Jak-Stat signaling pathway, reversing gut microbiota alterations, suppressing macrophage M1 polarization, maintaining the Th17/Treg cell balance, and reducing sustained inflammatory cytokines-related inflammatory injury.

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