白头翁汤通过抑制亮氨酸相关mTORC1信号和减少氧化应激缓解DSS诱导的溃疡性结肠炎

Abstract

Ethnopharmacological relevance Baitouweng decoction (BTW) has been used for hundreds of years to treat ulcerative colitis (UC) in China and has produced remarkable clinical results. However, the knowledge in protective mechanism of BTW against UC is still unclear. Aim of the study The present study was designed to investigate the anti-UC effects of BTW and the underlying mechanisms involved. Methods 3.5% dextran sulfate sodium (DSS)-induced experimental colitis was used to simulate human UC and the mice were treated with BTW (6.83 g/kg), leucine (200 mg/kg, Leu) or rapamycin (2 mg/kg, RAPA) as a positive control for 7 days. The clinical symptoms, serum myeloperoxidase (MPO) and malondialdehyde (MDA) levels were evaluated. Biological samples were collected to detect the effects of BTW on mechanistic target of rapamycin complex 1 (mTORC1) pathway and Leu metabolism. Results In our study, BTW notably improved the clinical symptoms and histopathological tissue damage and reduced the release of proinflammatory cytokines, including IL-6, IL-1β and TNF-α in UC mice. BTW also alleviated oxidative stress by decreasing serum MPO and MDA levels. Additionally, BTW significantly suppressed mTORC1 activity in the colon tissues of UC mice. Serum metabolomics analysis revealed that the mice receiving BTW had lower Leu levels, which was in line with the decreased expression of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in the colon tissues. Furthermore, oral administration of Leu aggravated DSS-induced acute colitis and enhanced mTORC1 activity in the colon. Conclusion These data strongly demonstrated that BTW could ameliorate DSS-induced UC by regulating the Leu-related mTORC1 pathway and reducing oxidative stress.