Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions

mice compared to wild-type (WT) mice. In these knockout mice, the content of wogonin was increased in the plasma but decreased in the colon tissues, suggesting that deficiencies in BCRP and MRP2 hinder the efflux of wogonin, resulting in elevated content in the plasma. Moreover, in vitro results showed that after knockout of BCRP and MRP2, the concentration of wogonin increased, and its UGT metabolite wogonoside decreased in both cells and mitochondria. These indicate that inhibiting efflux transporters suppresses cellular and mitochondrial glucuronidation metabolism. Interestingly, proteomic sequencing of mitochondrial subcellular organelles revealed that wogonin exhibited anti-UC effects by inhibiting afamin (AFM), with these effects modulated by BCRP and MRP2. These findings not only suggest a new mechanism for the anti-UC effects of wogonin, but also provide a pharmacological foundation for the clinical use of wogonin in treating UC.