Protective effects of 18β‐Glycyrrhetinic acid against myocardial infarction: Involvement of PI3K/Akt pathway activation and inhibiting Ca2+ influx via L‐type Ca2+ channels

Abstract

Abstract 18β‐Glycyrrhetinic acid (18β‐GA) is a component extracted from licorice. This study aimed to evaluate the effects of 18β‐GA on isoproterenol (ISO)‐induced acute myocardial infarction in rats and mice. Two consecutive days of subcutaneous injection of ISO (85 mg/kg/day) resulted in acute myocardial infarction. We examined the pathological changes, oxidative stress, inflammatory response, and expression of apoptosis in mouse hearts. The expressions of phosphoinositol‐3‐kinase (PI3K), protein kinase B (Akt), and the phosphorylation levels of PI3K (p‐PI3K) and Akt (p‐Akt) were determined by western blotting. The whole‐cell patch‐clamp technique was applied to observe the L‐type Ca2+ currents, and the Ion Optix detection system was used for cell contraction and Ca2+ transient in isolated rat cardiac ventricular myocytes. In ISO‐induced myocardial infarction, the J‐point, heart rate, creatine kinase, lactate dehydrogenase, superoxide dismutase, catalase, malondialdehyde, glutathion, and reactive oxygen species decreased in mice after 18β‐GA treatment. 18β‐GA improved ISO‐induced morphologic pathology, inhibited the inflammatory pathway response and cardiomyocyte apoptosis, and inhibited PI3K/Akt signaling. 18β‐GA could significantly inhibit ICa‐L, myocardial contraction, and Ca2+ transient. This study demonstrates that 18β‐GA has cardioprotective effects on acute myocardial infarction, which may be related to inhibiting oxidative stress, inflammation, apoptosis via the PI3K/Akt pathway, and reducing cell contractility and Ca2+ concentration via L‐type Ca2+ channels.

Keywords

• 18β‐Glycyrrhetinic acid
• Ca2+ transients
• cell contractility
• L‐type Ca2+ channels
• myocardial infarction
• PI3K/Akt signaling