Apigenin attenuates visceral hypersensitivity in water avoidance stress rats by modulating the microbiota-gut-brain axis and inhibiting mast cell activation

Visceral hypersensitivity (VH) and gut microbiota dysbiosis significantly contribute to the occurrence and development of irritable bowel syndrome (IBS), exacerbated by stress. Apigenin, a natural flavonoid derived from plants, possesses a range of beneficial properties. However, additional research is necessary to investigate its potential in alleviating symptoms of IBS and elucidating its underlying mechanisms of action. Our study confirms that apigenin effectively reverses mast cell and microglial activation, regulates the composition and abundance of the gut microbiota, improves intestinal barrier function in rats induced with water-avoidance stress, and mitigates VH and colonic hypermotility. Furthermore, in vitro studies suggest a potential role of dysbiotic gut microbiota in activating mast cells at the cellular level. Notably, apigenin inhibits mast cell degranulation through the toll-like receptor 4 (TLR4) / myeloid differentiation primary response gene 88 (MyD88) / nuclear factor-kappa B (NF-κB) pathway. In conclusion, this study discusses the potential therapeutic effects of apigenin in alleviating VH and modulating the gut-brain axis in water-avoidance stress rats, providing a novel or alternative treatment approach for IBS.