Transcriptomic analysis and experiment to verify the mechanism of Xiaoyao san in the treatment of irritable bowel syndrome with depression.

ETHNOPHARMACOLOGICAL RELEVANCE

Xiaoyao san (XYS) is a classic traditional Chinese medicine compound first recorded in "Taiping Huimin Heji Ju Fang". Traditionally, it is used to treat irritable bowel syndrome (IBS) and depression. However, its mechanism of action in treating IBS patients with depressive symptoms is still unclear.

AIM OF THE STUDY

This study aimed to investigate the effects of XYS on intestinal and depressive symptoms in IBS and explore the mechanisms through transcriptomic analysis and pharmacological experiments.

MATERIALS AND METHODS

IBS was induced in mice through a combination of chronic unpredictable mild stress and intragastric senna leaf stimulation. We evaluated six depressive parameters, examined colon tissue with hematoxylin and eosin staining and transmission electron microscopy, analyzed related proteins using western blotting, and performed transcriptomics on brain and intestinal tissues. The possible mechanism of action was speculated by network analysis of transcriptome results and further verified using the IBS model.

RESULTS

The results show that XYS restored mouse weight, reduced intestinal symptoms and sensitivity, suppressed villous loss and atrophy, and enhanced the integrity of the intestinal mucosal barrier. Notably, XYS decreased the depression-like behavior. Transcriptomic analysis combined with pharmacological experiments revealed that XYS inhibited the expression of proteins related to the intestinal ACT1/TRAF6/P38MAPK/AP-1 signaling pathway while activating the brain's DRD2/TH signaling pathway and increasing dopamine release in the brain.

CONCLUSIONS

XYS may regulate the brain-gut axis function and improve intestinal and depressive symptoms in IBS model mice through the intestinal ACT1/TRAF6/P38MAPK/AP-1 signaling pathway and the brain DRD2/TH signaling pathway.