Dihydroquercetin regulated PPARγ/AVPR1A/PLCB1/PLA2 pathway to alleviate the colitis of DSS mice.
Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that dihydroquercetin (DHQ) exerts anti-oxidative, anti-inflammatory and cell-protective properties as a natural occurring flavonoid compound, but its effects on IBD remain unclear. In this study, the mice were administered DHQ or fecal transplantation (FMT) followed by DSS administration, after which colitis symptoms, inflammation levels and intestinal barrier function were evaluated. Transcriptome and metabolome analysis of colon were conducted to explore the pathogenesis of colitis. Lastly, we analyzed the potential molecular mechanisms of DHQ in treating colitis by integrating network pharmacology, molecular docking technology and molecular biology experiments. DHQ or FMT protected mice from DSS-induced colitis, suppressed the inflammation and restored the weakened epithelial barrier. Transcriptome and metabolome analysis indicated that decreasing phospholipid level generated by phospholipase D signaling pathway (AVPR1A/PLCB1/PLA2) activation in colon mediated the occurrence of DSS-induced colitis. DHQ or FMT reversed the colitis of mice by regulating PPARγ/AVPR1A/PLCB1/PLA2 pathway. This research firstly discovers that increased phospholipid breakdown caused by PPARγ/AVPR1A/PLCB1/PLA2 leads to the disruption of the intestinal barrier and the occurrence of DSS-induced colitis. This research also provides new perspectives for understanding the pathogenesis of colitis and the protective effects of DHQ.