Yangweishu Granules Prevent Stress Gastric Ulcer by Inhibition of TLR4/MyD88/IKB-α Signaling Pathway

INTRODUCTION: This study aimed to investigate the therapeutic effect and mechanism of Yangweishu granules (YWS) for stress gastric ulcer (SGU). METHODS: The rat SGU model was established using the water immersion restraint stress method (WIRS). The therapeutic effect of YWS was evaluated by observing the histological changes of the stomach tissue, the levels of inflammatory factors, and oxidative stress. Meanwhile, the potential core targets and signaling pathways of YWS in anti-SGU action were analyzed using network pharmacology methods, and the related pathways were experimentally verified. RESULTS: YWS decreased the expressions of TNF-α, IL-1β, IL-6, and MDA in serum, and increased the levels of IL-4, IL-10, SOD, and GSH-PX. Network pharmacology analysis suggested that YWS may act on the targets of TLR4, AKT1, IL-10, TNF-α, IL-1β, and TP53 through the toll-like receptor pathway to treat SGU. RT-PCR, immunohistochemical, and Western blot results showed that YWS significantly inhibited the TLR4/MyD88/IKB-α pathway. Molecular docking results showed that the main active component of YWS could bind tightly to the TLR4 protein. DISCUSSION: This study established an animal model of SGU and preliminarily investigated the therapeutic effects and mechanism of YWS. To more comprehensively evaluate its application value in the treatment of peptic ulcers, subsequent studies should construct various types of ulcer models, further systematically assess the efficacy of YWS, and deeply explore its potential mechanism. CONCLUSION: YWS could alleviate WIRS-induced SGU in rats, and its potential mechanism was found to involve the inhibition of the TLR4/MyD88/ IKB-α signaling pathway.