Cardioprotective effects of notoginsenoside R1 on myocardial remodeling and cardiac function in restraint stress-induced MI in rats.

Abstract

Myocardial infarction (MI) is one of the leading causes of death globally, and stress-aggravated cardiac injury exacerbates patient prognosis. The study aimed to clarify the role of notoginsenoside R1 (NR) in the myocardial infarction-induced differential gene 2 (CRIF1)/PINK1-Parkin complex by using a restrain stress-exacerbated MI rat model. Male Sprague Dawley rats were subjected to coronary artery ligation followed by treatment with NR (2.5, 5, or 10 mg/kg, p.o.) for 10 days post-surgery. NR significantly enhanced cardiac function (elevated LVEF (left ventricular ejection fraction), LVFS (left ventricular fractional shortening), LVEDD (left ventricular end diastolic diameter), LVESD (left ventricular end systolic diameter)) and attenuated serum markers of myocardial damage (LDH (lactate dehydrogenase), CK-MB (creatine kinase myocardial band), CPK (creatine phosphokinase), cTnT (cardiac troponin T), cTnI (cardiac Troponin I)). It brought the imbalanced electrolyte status back to equilibrium, increased antioxidants, and decreased inflammatory mediators and apoptotic markers. In addition, NR suppressed NF-κB (nuclear kappa B factor) and NOX (NADPH oxidase 1) isoforms but increased the expression of PINK1-Parkin-associated mitochondrial quality control genes and cardiac remodeling markers at mRNA levels. These results indicate that NR exerts cardioprotection by inhibiting oxidative stress, inflammation, and apoptosis via the coordinated regulation of NF-κB/NOX/PINK1-Parkin signaling. However, additional protein-level validation (Western blot) and pathway inhibition studies together with the mechanistic confirmation are warranted in order to promote a causal role and translational potential.