BACKGROUND: Functional dyspepsia (FD), characterized by complex pathophysiology and limited therapeutic options, is a prevalent gastrointestinal disorder. Wei-Dong Granules (WDGs) demonstrate significant clinical efficacy in FD treatment; however, their underlying mechanisms require elucidation.
PURPOSE: To investigate the therapeutic effects of WDGs on FD and delineate the associated molecular mechanisms.
METHODS: An FD rat model was established using neonatal iodoacetamide-induced transient gastric injury followed by tail clamping and alternate-day fasting in adulthood. Rats received WDGs via gavage. Gastric motility (food intake, gastric emptying rate, residual food volume), behavioral symptoms, serum gastrointestinal hormones (Motilin, Gastrin, Ghrelin, CCK), and inflammatory factors were assessed. Gastric mucosal damage and repair were evaluated by H&E, Masson, TUNEL, and CD45 staining histologically. After that, UPLC-MS was carried out to identify chemical profiling of WDGs. Transcriptomics of gastric tissues and gut microbiota analysis of intestinal contents were performed, followed by multi-omics integration. ELISA, qPCR, immunohistochemistry, western blot, Masson staining, TUNEL staining, and CD45 staining were conducted to validate the proposed mechanism.
RESULTS: WDG treatment significantly improved FD symptoms, evidenced by increased food intake and gastric emptying rate, decreased gastric residual volume, and alleviated behavioral abnormalities. WDGs mitigated gastric mucosal damage and promoted glandular and mucosal regeneration. It regulated gastrointestinal hormones (elevated Motilin, Gastrin, Ghrelin; decreased CCK) and reduced IL-6 levels. UPLC-MS identified 174 chemical components in WDG, with 132 confirmed by standards, predominantly flavonoids (50), organic oxides (26), and prenol lipids (23). Multi-omics analysis indicated that WDGs modulated gut microbiota dysbiosis (e.g., Bacteroides, Peptostreptococcus, Ruminococcus), promoted short-chain fatty acid (SCFA) production, activated the vagus nerve-hypothalamus Ghrelin pathway via the gut-brain axis, regulated gastrointestinal hormone secretion, enhanced antioxidant capacity, and facilitated gastric mucosal repair. Subsequent validation confirmed that WDGs alleviated FD through multi-targeted actions encompassing enhanced motility, anti-inflammation, antioxidant effects, and mucosal repair.
CONCLUSION: WDGs effectively treat FD by orchestrating gut microbiota-SCFA-gut-brain axis signaling, which enhances gastric motility, reduces inflammation and oxidative stress, and promotes mucosal repair. This integrated study elucidates the mechanism of WDGs and provides a scientific foundation for its clinical application in FD therapy.
