Deciphering the pharmacological mechanisms of Weiweisu decoction in chronic atrophic gastritis: Insights from network pharmacology, molecular dynamics, and in vivo validation.

BACKGROUND

This study aims to identify the phytochemical components of Weiweisu (WWS) decoction, evaluate its therapeutic potential for chronic atrophic gastritis (CAG), and elucidate the underlying mechanisms with a focus on antiferroptotic effects.

METHODS

Liquid chromatography-mass spectrometry was used to characterize the phytochemical constituents of WWS. Network pharmacology was applied to predict potential therapeutic targets and signaling pathways. Core compounds and targets were verified through molecular docking and molecular dynamics simulations. Subsequently, a CAG rat model was established. Enzyme-linked immunosorbent assay was used to measure levels of prostaglandins (pepsinogen I/II) and tumor necrosis factor-α in gastric tissue, while Fe2+, glutathione, and malondialdehyde concentrations were assessed. Gene and protein expression levels of key targets were analyzed using quantitative real-time polymerase chain reaction and western blotting.

RESULTS

A total of 1017 chemical constituents were identified via liquid chromatography-mass spectrometry. Network pharmacology revealed 20 ferroptosis-related genes associated with WWS and CAG, primarily involving cancer-related signaling pathways. In vivo experiments showed that WWS ameliorated gastric ulcers and mucosal atrophy, downregulated pepsinogen I/II and tumor necrosis factor-α levels, reduced Fe2+ and malondialdehyde concentrations, and increased glutathione levels. WWS treatment also elevated HSP90AA1, MAPK, and mTOR expression while inhibiting GPX4 expression. Molecular docking indicated strong binding affinities between key active compounds and core targets. Molecular dynamics simulations confirmed the stability of these interactions.

CONCLUSION

In summary, WWS decoction can treat CAG through antiferroptosis, and its main mechanism may be related to the regulation of tumor signaling pathways.