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

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

  • J Pharm Pharmacol. 2023 Nov 25:rgad091. doi: 10.1093/jpp/rgad091.
Yue Li 1,  Xia Yang 2,  Jicheng Han 1,  Bing Bai 1,  Yaru Li 2,  Chao Shang 3,  Shanzhi Li 1,  Zhiru Xiu 1,  Zirui Liu 3,  Chenchen Ge 3,  Guangze Zhu 1,  Ningyi Jin 1 3,  Jinbo Fang 1,  Yiquan Li 1,  Xiao Li 1 3,  Yilong Zhu 1
Affiliations

Affiliations

  • 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.
PMID: 38007392 DOI: 10.1093/jpp/rgad091
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.

Keywords

Jak–Stat pathway; Th17/Treg cell balance; gut microbiota; inflammatory cytokines; macrophage M1 polarization; peimisine.

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