Efficacy of Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rat.

Abstract

To elucidate the protective effects of Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction (MI) through regulating myocardial autophagy. Thirty-one male Sprague-Dawley rats were randomized into five groups (n = 6 or 7 for each). After treatment for 3 weeks, electrocardiogram ( ECG ) and cardiac function were recorded. Hematoxylin and eosin (HE) staining was used to detect pathological changes in the heart. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum B-type brain natriuretic peptide (BNP), cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), and serum inflammatory cytokines. Metabolomic analysis was used to identify differential biomarkers of MI in rats. Immunohistochemistry and western blotting were used to detect BNP, cTnT, TNF-α, LC3B, Beclin-1, p62, and adenosine monophosphate activated protein kinase (AMPK) expression in cardiac tissue. Fuzi (Radix Aconiti Lateralis Preparata) alone or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) markedly ameliorated cardiac dysfunction and abnormal ECGs, demonstrated by decreases in the heart weight/body weight ratio, BNP, and cTnT. Pro-inflammation cytokine interleukin (IL)-1α significantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen (Radix Ginseng) single or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) groups compared with the control group. HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen (Radix Ginseng) or Fuzi (Radix Aconiti Lateralis Preparata) alone. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) reversed these changes to different degrees in MI rats. Furthermore, Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) down-regulated LC3B, Beclin-1, and AMPK expression in cardiac tissue and upregulated p62 expression. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) may have a greater effect on heart injury induced by MI in rats than Fuzi (Radix Aconiti Lateralis Preparata) treatment alone, and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects. These results provide fresh insight into the mechanism of co-treatment with Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) for MI.