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

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-05-03 DOI:10.1093/jpp/rgad091

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

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Abstract

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-1β, IL-6, IFN-γ, TNF-α 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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培咪辛通过抑制小鼠Jak-Stat激活和缓解肠道菌群失调来改善dss诱导的结肠炎。

目的:炎性细胞因子分泌和肠道菌群失调在溃疡性结肠炎中起重要作用。本研究探讨贝米辛对结肠炎小鼠的保护作用。方法:采用疾病活动性指数、结肠长度、苏木精-伊红染色、AB/PAS染色评价其保护作用。采用ELISA、Western-blot、免疫组织化学染色、免疫荧光染色、16S rRNA基因分析等方法分析其保护机制。结果表明，培咪嗪治疗可降低疾病活动指数，防止结肠缩短，减轻结肠组织损伤。培咪素还通过下调jak1/2、p-jak1/2、stat1/3、p-stat1/3的表达，降低MCP-1、IL-1β、IL-6、IFN-γ、TNF-α水平，影响巨噬细胞极化和Th17/Treg细胞平衡。培米辛处理显著提高了瘤胃球菌科(Ruminococcaceae) UCG-014和Lachnospiraceae_NK4A136_group等有益微生物的丰度，降低了拟杆菌(Bacteroides)和埃希氏菌(Escherichia)等有害微生物的丰度。结论:培咪嗪可通过抑制Jak-Stat信号通路，逆转肠道菌群改变，抑制巨噬细胞M1极化，维持Th17/Treg细胞平衡，减轻炎性细胞因子相关的持续性炎症损伤，改善结肠炎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.

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