Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome

Yucui Zhao; Jiaguo Zhan; Congying Sun; Shixiao Zhu; Yue Zhai; Yongna Dai; Xiaoying Wang; Xiumei Gao

doi:10.1016/j.phymed.2024.155541

Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome

Phytomedicine. 2024 Mar 18:129:155541. doi: 10.1016/j.phymed.2024.155541. Online ahead of print.

Authors

Yucui Zhao¹, Jiaguo Zhan¹, Congying Sun¹, Shixiao Zhu¹, Yue Zhai¹, Yongna Dai², Xiaoying Wang³, Xiumei Gao⁴

Affiliations

¹ Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: daiyongna@tjutcm.edu.cn.
³ Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: wxy@tjutcm.edu.cn.
⁴ Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: gaoxiumei@tjutcm.edu.cn.

PMID: 38579640
DOI: 10.1016/j.phymed.2024.155541

Abstract

Background: Diarrheal irritable bowel syndrome (IBS-D), characterized primarily by the presence of diarrhea and abdominal pain, is a clinical manifestation resulting from a multitude of causative factors. Furthermore, Sishen Wan (SSW) has demonstrated efficacy in treating IBS-D. Nevertheless, its mechanism of action remains unclear.

Methods: A model of IBS-D was induced by a diet containing 45 % lactose and chronic unpredictable mild stress. Additionally, the impact of SSW was assessed by measuring body weight, visceral sensitivity, defecation parameters, intestinal transport velocity, intestinal neurotransmitter levels, immunohistochemistry, and transmission electron microscopy analysis. Immunofluorescent staining was used to detect the expression of Mucin 2 (MUC2) and Occludin in the colon. Western blotting was used to detect changes in proteins related to tight junction (TJ), autophagy, and endoplasmic reticulum (ER) stress in the colon. Finally, 16S rRNA amplicon sequencing was used to monitor the alteration of gut microbiota after SSW treatment.

Results: Our study revealed that SSW administration resulted in reduced visceral sensitivity, improved defecation parameters, decreased intestinal transport velocity, and reduced intestinal permeability in IBS-D mice. Furthermore, SSW promotes the secretion of colonic mucus by enhancing autophagy and inhibiting ER stress. SSW treatment caused remodeling of the gut microbiome by increasing the abundance of Blautia, Muribaculum and Ruminococcus torques group.

Conclusion: SSW can improve intestinal barrier function by promoting autophagy and inhibiting ER stress, thus exerting a therapeutic effect on IBS-D.

Keywords: Colonic mucus; Diarrheal irritable bowel syndrome; Endoplasmic reticulum stress; Sishen Wan.