The present study is aimed at investigating whether Qiliqiangxin (QL) could regulate myocardial energy metabolism in heart failure rats after acute myocardial infarction (AMI) and further exploring the underlying mechanisms. AMI was established by ligating the left anterior descending coronary artery in adult male SD rats. AMI rats with ejection fraction (EF) < 50% at two weeks after the operation were chosen as heart failure rats for the main study. Rats were randomized into the sham, MI, MI+QL, and MI+QL+2‐MeOE2 groups. The results showed that compared with the MI group, QL significantly improved cardiac function, reduced serum NT‐proBNP level, and alleviated myocardial fibrosis. QL also increased myocardial capillary density by upregulated protein expressions of vascular endothelial growth factor (VEGF) and CD31 by regulating the HIF‐1α/VEGF pathway. Moreover, QL promoted ATP production, glucose uptake, and glycolysis by upregulating HIF‐1α and a series of glycolysis‐relevant enzymes in a HIF‐1α‐dependent manner. QL also improved myocardial glucose oxidation enzyme expression and free fatty acid uptake by a HIF‐1α‐independent pathway. Our results indicate that QL treatment improves cardiac function through regulating glucose uptake, FFA uptake, and key enzymes of energy metabolism via HIF‐1α‐dependent and independent mechanisms.

Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The present study aims to explore whether Qiliqiangxin (QL) can benefit cardiac diastolic function in spontaneously hypertensive rat (SHR) through enhancement of cardiac glucose metabolism. Fifteen 12‐month‐old male SHRs were randomly divided into QL‐treated, olmesartan‐treated, and saline‐treated groups. Age‐matched WKY rats served as normal controls. Echocardiography and histological analysis were performed. Myocardial glucose uptake was determined by ¹⁸F‐FDG using small‐animal PET imaging. Expressions of several crucial proteins and key enzymes related to glucose metabolism were also evaluated. As a result, QL improved cardiac diastolic function in SHRs, as evidenced by increased E^′/A^′and decreased E/E^′ (P < 0.01). Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and apoptosis (P < 0.01). An even higher myocardial glucose uptake was illustrated in QL‐treated SHR group (P < 0.01). Moreover, an increased CS activity and ATP production was observed in QL‐treated SHRs (P < 0.05). QL enhanced cardiac glucose utilization and oxidative phosphorylation in SHRs by upregulating AMPK/PGC‐1α axis, promoting GLUT‐4 expression, and regulating key enzymes related to glucose aerobic oxidation such as HK2, PDK4, and CS (P < 0.01). Our data suggests that QL improves cardiac diastolic function in SHRs, which may be associated with enhancement of myocardial glucose metabolism.