Baitouweng decoction regulates ferroptosis-mediated mitophagy and apoptosis through the SLC7A11/GPX4/FTH1 pathway in ulcerative colitis.

[BACKGROUND] The prevalence of ulcerative colitis (UC) has increased recently, with severe cases potentially progressing to colon cancer. The classic herbal formula Baitouweng Decoction (BTW) has a centuries-long clinical application in UC treatment, but its underlying mechanism remains unclear.

[PURPOSE] This study aimed to investigate BTW's efficacy against Dextran Sodium Sulfate (DSS)-induced UC and clarify its mechanisms.

[RESULTS] Proteomic analysis identified ferroptosis as a key pathogenic mechanism in UC. In vitro and in vivo experiments showed that BTW reduced UC-associated inflammatory symptoms, normalized the levels of inflammatory factors, and maintained intestinal barrier integrity. Notably, BTW inhibited ferroptosis and restored the antioxidant capacity of the SCL7A11/GSH/GPX4 system, thereby suppressing UC inflammation. Transcriptomic analysis revealed apoptosis and ferroptosis as core pathways for BTW's intervention in UC, with mitophagy serving as a pivotal hub connecting these processes. BTW regulated the PINK1/PARKIN-mediated mitophagy pathway and apoptosis, and this regulation was closely linked to ferroptosis.

[CONCLUSION] BTW alleviates UC-related inflammation and intestinal barrier damage by modulating apoptosis, mitophagy, and ferroptosis, while mitigating oxidative stress.