Abstract

Doxorubicin (DOX) is a potent chemotherapeutic drug, whose clinical application is largely restricted by dose-dependent cardiotoxicity (DIC). Dracocephalum moldavica L. is a classic medicinal and edible plant with obvious cardiovascular protective effects; however, the role of its total flavonoids (TFDM) in DIC remains unclear. This study explored the cardioprotective effect of TFDM on DOX-induced myocardial injury and its mechanism related to mitochondrial quality control. We established in vivo and in vitro DIC models and adopted echocardiography, detection of cardiac injury and oxidative stress indicators, transmission electron microscopy, mitochondrial functional assessment and Western blotting, with AMPK knockdown performed for mechanism verification. Results showed that TFDM effectively improved cardiac function, reduced myocardial oxidative stress and apoptosis, and maintained mitochondrial ultrastructure and energy metabolism. TFDM activated the AMPK/PGC1α signaling axis to facilitate mitochondrial biogenesis, and AMPK silencing eliminated the protective effect of TFDM. In conclusion, AMPK/PGC-1α pathway is a primary key pathway involved in TFDM’s protective effects, which provides an experimental basis for the development of Dracocephalum moldavica L. as a functional food and adjuvant agent against DIC.