Yangweishu granules in treating chronic atrophic gastritis with spleen-stomach dampness-heat syndrome: An integrated study on its mechanism using multiple technologies.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Yangweishu (YWS) is a traditional Chinese herbal formula widely used in the clinical treatment of Chronic atrophic gastritis (CAG). However, its therapeutic mechanism in CAG with spleen-stomach dampness-heat syndrome (SSDHS) remains to be fully elucidated. AIM OF THE STUDY: This study aimed to investigate the therapeutic efficacy and underlying mechanisms of YWS in SSDHS-CAG through an integrated strategy combining network pharmacology, ADMET analysis, molecular docking, molecular dynamics and experiments validation. METHODS: An SSDHS rat model was established using a high-fat/high-sugar diet and artificial climate exposure, and multi-factor induction. YWS efficacy was evaluated through histopathological examination and biochemical assays. Network pharmacology predicted potential targets and pathways. Key YWS components were analyzed using ADMET analysis, molecular docking, and dynamics simulations. Critical predictions were validated by Western blot, q-PCR, and immune cell function assays. RESULTS: YWS administration significantly improved body weight, restored thymus and spleen indices, reduced SSDHS scores, and alleviated gastric histopathology in SSDHS-CAG rats. YWS also decreased the levels of IL-1β, IL-6 and MDA, while increasing SOD activity. Network pharmacology identified the MAPK pathway as a key target. ADMET profiling suggested favorable pharmacokinetics for the YWS components. Molecular docking and dynamics simulations demonstrated high-affinity binding of Harpagoside, Hesperidin, and Chlorogenic acid to the ERK and JNK proteins. Experimental validation confirmed that YWS normalized the CD4/CD8T-cell ratio, curbed excessive T and B cell proliferation, and markedly downregulated the phosphorylation and mRNA expression of JNK and ERK in gastric mucosa. CONCLUSION: YWS exerts therapeutic effects against SSDHS-CAG by inhibiting the ERK/JNK signaling pathway, attenuating inflammatory responses and oxidative stress, and restoring immune homeostasis. These findings provide a pharmacological basis for the clinical application of YWS in treating SSDHS-CAG and offer a foundation for further investigation into its active constituents and molecular mechanisms.