Prophylactic administration of Kanli granule maintains fatty acid oxidation in the myocardium to prevent heart failure via activating AMPK/PPARα/CPT1A pathway: A network pharmacology-based study.

BACKGROUND

Abnormal energy metabolism plays a crucial role in the pathogenesis of heart failure (HF). Kanli granule (KLG), as an effective herbal medicine for treating HF, has been used in clinical practice for nearly 30 years. However, its underlying mechanisms have not been fully elucidated.

METHODS

This study combined network pharmacology, molecular docking, and in vivo experiments to explore KLG's effect on HF. Wistar rats with AAC-induced HF were orally administered KLG (0.675/1.35/2.7 g/kg) for 32 weeks. Assessments included heart weight index, echocardiography, histopathology, fatty acid metabolism (FAM) targets, and myocardial energy metrics. We focused on fatty acid oxidation (FAO) pathway, measuring AMPK, PPARα, and CPT1A at protein and gene levels.

RESULTS

KLG maintained cardiac function in AAC rats. Network pharmacology identified PPAR and AMPK pathways as key in FAM. Molecular docking showed strong affinity of KLG components to FAO targets PPARα and CPT1A. KLG significantly enhanced myocardial energy metabolism, reduced myocardial FFA levels, and increased ATP/ADP ratios. It activated AMPK and upregulated FAO-related genes, including PPARα and CPT1A.

CONCLUSION

KLG improves FAO in AAC-induced HF rats by activating the AMPK/PPARα/CPT1A pathway, reducing myocardial FFA levels, and improving myocardial microstructure and cardiac function.