Free radical biology & medicine · 2026
Salvianolic acid B ameliorates metabolic dysfunction-associated steatohepatitis in mice by inhibiting hepatocyte ferroptosis via regulation of the SIRT1/p53 axis.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhou Xiaoxi, Lv Jinxin, Liu Wei, Mu Yongping, Chen Gaofeng, Chen Jiamei, Liu Ping, Fu Yadong
Аннотация
BACKGROUND: MASH has become the most prevalent chronic liver disease worldwide. Hepatocyte ferroptosis is a key driver in the progression of MASH. Salvianolic acid B (Sal B), a natural antioxidant active ingredient, has an anti-MASH effect. However, the underlying mechanism by which Sal B inhibits hepatocyte ferroptosis and improves MASH remains unclear.
METHODS: An in vivo MASH model was established by feeding C57BL/6J mice a HFHC diet for 30 weeks. In the 24th week, mice were treated with Sal B, obeticholic acid (OCA) or SRT1720. In vitro, over-expression and knockdown of SIRT1 in hepatocytes were constructed with lentivirus, subsequently, a hepatocyte lipid deposition model induced by palmitic acid/oleic acid (PO) or a hepatocyte ferroptosis model induced by erastin were used to investigate the efficacy and mechanism of Sal B. Furthermore, the interaction and binding kinetics of Sal B and SIRT1 were determined by molecular docking simulation, DARTS, CETSA and SPR assays.
RESULTS: Sal B attenuated hepatic inflammation, lipid deposition and fibrosis in MASH mice. In situ transmission electron microscopy revealed characteristic morphological features of hepatocyte ferroptosis in the livers of MASH mice, which were alleviated by Sal B treatment. Mechanistically, Sal B up-regulated hepatic SIRT1 protein and inhibited p53 acetylation. In vitro, Sal B alleviated PO- or erastin-induced lipid deposition and ferroptosis in hepatocytes, along with up-regulating SIRT1 and inhibiting p53 acetylation. Similar protective effects were observed upon SIRT1 overexpression. Strikingly, SIRT1 knockdown reduced the inhibitory effect of Sal B on hepatocyte ferroptosis. SPR analysis confirmed moderate-affinity binding of Sal B to recombinant human SIRT1 protein, while DARTS and CETSA assays indicated that Sal B enhances SIRT1 enzymatic and thermal stability.
CONCLUSION: Sal B ameliorates MASH in mice via directly regulating SIRT1/p53 signaling to suppress hepatocyte ferroptosis. Targeting hepatocyte ferroptosis through SIRT1 activation is a promising therapeutic strategy for MASH.
METHODS: An in vivo MASH model was established by feeding C57BL/6J mice a HFHC diet for 30 weeks. In the 24th week, mice were treated with Sal B, obeticholic acid (OCA) or SRT1720. In vitro, over-expression and knockdown of SIRT1 in hepatocytes were constructed with lentivirus, subsequently, a hepatocyte lipid deposition model induced by palmitic acid/oleic acid (PO) or a hepatocyte ferroptosis model induced by erastin were used to investigate the efficacy and mechanism of Sal B. Furthermore, the interaction and binding kinetics of Sal B and SIRT1 were determined by molecular docking simulation, DARTS, CETSA and SPR assays.
RESULTS: Sal B attenuated hepatic inflammation, lipid deposition and fibrosis in MASH mice. In situ transmission electron microscopy revealed characteristic morphological features of hepatocyte ferroptosis in the livers of MASH mice, which were alleviated by Sal B treatment. Mechanistically, Sal B up-regulated hepatic SIRT1 protein and inhibited p53 acetylation. In vitro, Sal B alleviated PO- or erastin-induced lipid deposition and ferroptosis in hepatocytes, along with up-regulating SIRT1 and inhibiting p53 acetylation. Similar protective effects were observed upon SIRT1 overexpression. Strikingly, SIRT1 knockdown reduced the inhibitory effect of Sal B on hepatocyte ferroptosis. SPR analysis confirmed moderate-affinity binding of Sal B to recombinant human SIRT1 protein, while DARTS and CETSA assays indicated that Sal B enhances SIRT1 enzymatic and thermal stability.
CONCLUSION: Sal B ameliorates MASH in mice via directly regulating SIRT1/p53 signaling to suppress hepatocyte ferroptosis. Targeting hepatocyte ferroptosis through SIRT1 activation is a promising therapeutic strategy for MASH.