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

Author:

Li Yue1ORCID,Yang Xia2,Han Jicheng1,Bai Bing1,Li Yaru2,Shang Chao3,Li Shanzhi1,Xiu Zhiru1,Liu Zirui3,Ge Chenchen3,Zhu Guangze1,Jin Ningyi13,Fang Jinbo1,Li Yiquan1,Li Xiao13,Zhu Yilong1

Affiliation:

1. Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine , Changchun, Jilin 130117 , P. R. China

2. Medical College, Yanbian University , Yanji 133002 , P. R. China

3. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Changchun, Jilin 130122 , P. R. China

Abstract

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.

Funder

Jilin Science and Technology Development Plan Project

Young Scientist Program Training Program of Changchun University of Chinese Medicine

Jilin Traditional Chinese Medicine Science and Technology Project

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference67 articles.

1. Kuijieyuan decoction improved intestinal barrier injury of ulcerative colitis by affecting TLR4-dependent PI3K/AKT/NF-kappaB oxidative and inflammatory signaling and gut microbiota;Liu,2020

2. Gut microbiota regulation and anti-inflammatory effect of beta-carotene in dextran sulfate sodium-stimulated ulcerative colitis in rats;Zhu,2021

3. Inhibitor of differentiation-2 protein ameliorates DSS-induced ulcerative colitis by inhibiting NF-kappaB activation in neutrophils;Ren,2021

4. IL-6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac;Li,2021

5. Update on the therapeutic management of patients with either psoriatic arthritis or ulcerative colitis: focus on the JAK inhibitor tofacitinib;Chimenti,2021

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