Cardioprotective mechanisms of Jiangfu Decoction against myocardial ischemia may involve regulation of the AMPK/PINK1/Parkin mitochondrial autophagy pathway.

Abstract

BACKGROUND: Jiangfu Decoction (JFD) is a classical traditional herbal medicine used to clinically treat ischemic heart disease (IHD). Nonetheless, the influence of JFD on myocardial ischemia (MI), along with its precise underlying mechanism, is still unclear. The objective of this research was to investigate the potential mechanisms by which JFD exerts cardioprotective effects on MI induced by isoproterenol (ISO). METHODS: An acute MI model was established by subcutaneous injection of ISO (85 mg/kg/d). To evaluate alterations in myocardial structure, electrocardiogram recordings and heart histology examinations were employed. The myocardial ultrastructure was observed by transmission electron microscopy (TEM). Using specific kits, the levels and activities of oxidative stress markers as well as inflammatory cytokines were separately assessed. Western blotting was employed to assess the expression levels of proteins related to adenosine monophosphate-activated protein kinase (AMPK), PTEN-induced putative kinase 1 (PINK1), Parkin, Nod-like receptor protein 3 (NLRP3), and Caspase-1. RESULTS: The findings show that JFD treatments markedly diminished heart rate, pathological alterations in cardiac tissue, chondriosome injury, and serum concentrations of creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, malondialdehyde, interleukin-1β, and interleukin-18. Concurrently, these treatments augmented the activation of superoxide dismutase, catalase, and glutathione peroxidase in the serum of animals subjected to ISO treatment. Additionally, JFD also reversed the ISO-induced changes in the levels of AMPK, PINK1, Parkin, NLRP3, and Caspase-1. CONCLUSION: JFD exhibits a notable safeguarding influence on MI via a mechanism that involves regulation of the AMPK/PINK1/Parkin mitochondrial autophagy pathway, inhibition of pyroptosis, and reduction of oxidative stress and inflammation.