Multi-omics analysis reveals TCA cycle and mitochondrial metabolic remodeling associated with astragaloside IV-mediated cardioprotection

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and is closely related to metabolic dysfunction. Astragaloside IV (ASIV), as an effective component of Astragalus membranaceus (Fisch.) Bunge, which is both edible and medicinal, plays an important role in the prevention and treatment of DCM. However, the potential regulatory mechanisms underlying its cardioprotective effects have not been fully elucidated. In this study, high glucose-induced AC16 cardiomyocytes were used as an in vitro model, and integrated transcriptomic and metabolomic analyses were performed to investigate the interventional effects of ASIV. The results showed that ASIV partially reversed high glucose-induced transcriptional and metabolic abnormalities. Pathway enrichment analysis highlighted pyruvate metabolism, the tricarboxylic acid (TCA) cycle, and mitochondrial energy metabolism. PDHA1 was identified as a candidate transcriptional node associated with pyruvate metabolism, while evaluation of six detectable TCA cycle-associated metabolites revealed heterogeneous changes rather than a uniform restoration pattern. Gene–metabolite association analysis further indicated coordinated transcriptional and metabolic alterations. Collectively, these findings suggest that ASIV-associated cardioprotection is accompanied by partial remodeling of mitochondrial energy metabolism and TCA cycle-related metabolic homeostasis.