发表期刊：Phytomedicine

发表时间：2025

Abstract:

Background

Changan Granule (CAG) is a drug product developed from a traditional Chinese medicine (TCM) empirical prescription for diarrhea-predominant irritable bowel syndrome (IBS-D). The action mechanism and effective compounds of CAG in the treatment of IBS-D are not well understood.

Purpose

This study aimed to investigate the effectiveness, action mechanism and effective compounds of CAG for treating IBS-D.

Methods

Network pharmacology was used to screen the related pathways and active compounds of CAG in the treatment of IBS-D. Neonatal mother-infant separation, acetic acid enema and colorectal dilation were employed to construct IBS-D model for in vivo study. The effectiveness of CAG was evaluated in accordance with the results of body weight measurement, fecal water content determination, abdominal withdraw reflex test, open field test, sucrose preference test, forced swimming test and hematoxylin-eosin (HE) staining. The protein and mRNA levels of key molecules regulated by CAG were assessed through enzyme-linked immunosorbent assay (ELISA), western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The active compounds from CAG screened by network pharmacology were investigated with Caco-2 and RIN-14B cell models in vitro.

Results

Network pharmacological analysis showed that CAG regulated 5-hydroxytryptamine (5-HT) signaling pathway and tetrahydropalmatine, formononetin and corydaline might be the potential effective compounds. The validation experiments showed that CAG restored the decreased body weight, and alleviated intestinal sensitivity, low-grade inflammation, diarrhea, frequent defecation, anxiety and depression of IBS-D rats through regulating the expression levels of 5-HT, tryptophan hydroxylase (TPH)1/2, serotonin transporter (SERT), 5-hydroxytryptamine-3 and -4 receptors (5-HT3R and 5-HT4R) in brain-gut axis (BGA). Tetrahydropalmatine and formononetin were confirmed to be the potential effective compounds of CAG in regulating 5-HT signaling pathway.

Conclusion

CAG exhibits therapeutic effect on IBS-D rats through regulating 5-HT signaling pathway in BGA. Tetrahydropalmatine and formononetin are major potential effective compounds. Our findings provide scientific basis for the clinical use and drug development of CAG for IBS-D.

https://doi.org/10.1016/j.phymed.2024.156350