Efficacy of Shu-yi-ning-chang decoction on IBS-D: Modulating Nr4a3 pathway to reduce visceral hypersensitivity

作者全名：Guo, Yajing; Lu, Qiongqiong; Yang, Xiao-Jun; He, Yuxi; Wu, Yue; Qin, Baijun; Li, Ting; Duan, Min; Liu, Nvping; Wu, Xin; He, Yuanjun

作者地址：[Guo, Yajing; Yang, Xiao-Jun] Chengdu Univ Tradit Chinese Med, Dept Clin Med, Chengdu, Sichuan, Peoples R China; [Lu, Qiongqiong; Yang, Xiao-Jun; He, Yuxi; Wu, Yue; Qin, Baijun; He, Yuanjun] Chongqing City Hosp Tradit Chinese Med, Dept Gastroenterol, Chongqing, Peoples R China; [Li, Ting] Chongqing Med Univ, Dept Pharmaceut, Chongqing, Peoples R China; [Duan, Min] Hunan Univ Tradit Chinese Med, Changsha Hosp Tradit Chinese Med, Dept Clin Med, Changsha, Hunan, Peoples R China; [Liu, Nvping; Wu, Xin] Guizhou Univ Tradit Chinese Med, Dept Clin Med, Guiyang, Guizhou, Peoples R China

通信作者：Yang, XJ (通讯作者)，Chengdu Univ Tradit Chinese Med, Dept Clin Med, Chengdu, Sichuan, Peoples R China.; Yang, XJ (通讯作者)，Chongqing City Hosp Tradit Chinese Med, Dept Gastroenterol, Chongqing, Peoples R China.

来源：PLOS ONE

ESI学科分类：Multidisciplinary

WOS号：WOS:001239204800067

JCR分区：Q1

影响因子：2.9

年份：2024

卷号：19

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Aim of the study To evaluate the therapeutic effect of SYNC in diarrhea irritable bowel syndrome (IBS-D) and explore its underlying mechanism through transcriptomic sequencing (RNA-Seq).Materials and methods A rat model of IBS-D was constructed to elucidate the effects of SYNC. Abdominal withdrawal reflex (AWR), fecal water content (FWC), and recording body weight were calculated to assess visceral sensitivity in rats. Histopathological changes in the colon and alterations in mast cell (MC) count were determined. Immunohistochemistry was employed to assess mast cell tryptase (MCT) expression in rat colons. Serum levels of corticotropin-releasing Hormone (CRH), interleukin-6 (IL-6), calcitonin gene-related peptide (CGRP), and 5-hydroxytryptamine (5-HT) were quantified using ELISA. RNA-Seq of colon tissue was performed, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Western blot analysis was conducted to quantify the expression levels of key proteins in the Nr4a3 pathway in the colon and hypothalamus tissues of rats.Results SYNC alleviated visceral hypersensitivity and mood disorders in rats with IBS-D. Moreover, it was positively correlated with its dosage and the observed effects, such as the enhancement of the colon's mucosal lining condition and reduction in the number and activation of MCs within the model group. SYNC reduced the expression levels of factors related to the brain-gut axis and inflammatory markers in the bloodstream. RNA-Seq analysis indicated that SYNC down-regulated the expression of Nr4a3 and PI3K. These SYNC-targeted genes primarily played roles in immune regulation and inflammatory responses, correlating with the modulation of Nr4a3 and the PI3K/AKT pathway. Western blot analysis further confirmed SYNC's influence on inflammation-related MC activation by downregulating key proteins in the Nr4a3/PI3K pathway.Conclusions SYNC inhibited mast cell activation and attenuated visceral hypersensitivity in the colon tissues of IBS-D rats. These effects were mediated by the Nr4a3/PI3K signaling pathway.

基金机构：Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0858]; National Natural Science Foundation of China [82205085]

基金资助正文：Chongqing Natural Science Foundation (No: cstc2021jcyj-msxmX0858) and National Natural Science Foundation of China (82205085).