Archives of biochemistry and biophysics · 2026
Mitochondria-targeted cardioprotection of Gentianella acuta xanthones in doxorubicin-induced heart failure through AMPK/PGC-1α activation.
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.
Wei Yuxin, Yuan Huiyue, Wu Lihong, Yang Deqiang, Wang Meng, Sun Yanping, Wang Zhenyue, Kuang Haixue, Wang Zhibin
Аннотация
BACKGROUND: Heart failure (HF) is closely associated with mitochondrial dysfunction and impaired energy metabolism. Doxorubicin (DOX)-induced cardiomyopathy is a well-established model for investigating mitochondrial-driven HF. Gentianella acuta (GA), a traditional medicinal herb, has shown cardioprotective potential, yet the mechanisms of its major bioactive constituents, xanthones, in HF remain incompletely understood.
METHODS: A combined strategy integrating network pharmacology, in vitro cardiomyocyte injury models, and an in vivo DOX-induced HF rat model was employed to elucidate the cardioprotective mechanisms of GA-derived xanthones (XAN). Network pharmacology analysis was used to predict key targets and signaling pathways. Mitochondrial function, cardiomyocyte apoptosis, cardiac function, ultrastructural changes, energy metabolism indices, and AMPK/PGC-1α pathway-related proteins were systematically evaluated using H9c2 cells and HF rats.
RESULTS: Network pharmacology identified the AMPK signaling pathway as a key target of XAN in HF. In H9c2 cardiomyocytes, XAN attenuated DOX-induced mitochondrial membrane potential loss and apoptosis, accompanied by increased AMPK phosphorylation and upregulation of PGC-1α and SIRT1. In DOX-induced HF rats, XAN improved cardiac diastolic function, alleviated electrocardiographic abnormalities, reduced myocardial apoptosis, and preserved mitochondrial ultrastructure. XAN also restored myocardial energy metabolism by increasing ATP production and mitochondrial enzyme activities while reducing HF-related biomarkers. These effects were dose-dependent and closely associated with activation of the AMPK/PGC-1α pathway.
CONCLUSION: XAN confer mitochondria-targeted cardioprotection against DOX-induced HF by reprogramming myocardial energy metabolism via activation of the AMPK/PGC-1α pathway. These findings provide mechanistic evidence supporting XAN as promising natural candidates for metabolic intervention in HF.
METHODS: A combined strategy integrating network pharmacology, in vitro cardiomyocyte injury models, and an in vivo DOX-induced HF rat model was employed to elucidate the cardioprotective mechanisms of GA-derived xanthones (XAN). Network pharmacology analysis was used to predict key targets and signaling pathways. Mitochondrial function, cardiomyocyte apoptosis, cardiac function, ultrastructural changes, energy metabolism indices, and AMPK/PGC-1α pathway-related proteins were systematically evaluated using H9c2 cells and HF rats.
RESULTS: Network pharmacology identified the AMPK signaling pathway as a key target of XAN in HF. In H9c2 cardiomyocytes, XAN attenuated DOX-induced mitochondrial membrane potential loss and apoptosis, accompanied by increased AMPK phosphorylation and upregulation of PGC-1α and SIRT1. In DOX-induced HF rats, XAN improved cardiac diastolic function, alleviated electrocardiographic abnormalities, reduced myocardial apoptosis, and preserved mitochondrial ultrastructure. XAN also restored myocardial energy metabolism by increasing ATP production and mitochondrial enzyme activities while reducing HF-related biomarkers. These effects were dose-dependent and closely associated with activation of the AMPK/PGC-1α pathway.
CONCLUSION: XAN confer mitochondria-targeted cardioprotection against DOX-induced HF by reprogramming myocardial energy metabolism via activation of the AMPK/PGC-1α pathway. These findings provide mechanistic evidence supporting XAN as promising natural candidates for metabolic intervention in HF.