Peoniflorin Alleviates Corticotropin-Releasing Factor-Induced Irritable Bowel Syndrome by Improving the Intestinal Barrier Function through the Inhibition of the CRFR1/ROCK2/MLC Signaling Pathway.

Abstract

<p>Using paeoniflorin is a promising strategy for irritable bowel syndrome (IBS) therapy due to its natural origin and pharmacological activity. This study explored its therapeutic effects and mechanisms in corticotropin-releasing factor (CRF)-induced IBS models. In vitro, CRF disrupted tight junction (TJ) in T84 cells via the CRFR1/ROCK2/MLC pathway, downregulating occludin and claudin-1. Paeoniflorin targeted CRFR1, inhibited ROCK2 and MLC phosphorylation, and restored TJ integrity. In vivo, paeoniflorin alleviated anxiety-like behaviors and visceral hypersensitivity in CRF-induced IBS mice, reduced FITC-dextran levels, enhanced goblet cell mucus secretion, and improved intestinal permeability. It also upregulated occludin and claudin-1, restored TJ structure, and modulated the CRFR1/ROCK2/MLC pathway. These findings suggest paeoniflorin as a potential therapeutic agent for IBS-related intestinal barrier dysfunction.</p>