Mechanisms underlying the cardio-protection of total ginsenosides against myocardial ischemia in rats in vivo and in vitro: Possible involvement of L-type Ca2+ channels, contractility and Ca2+ homeostasis.

Abstract

Here we aimed to observe the effects of total ginsenosides (TG) against isoproterenol (ISO) induced myocardial ischemia (MI) and to explore its underlying mechanisms based on L-type Ca2+ current (ICa-L), intracellular Ca2+ ([Ca2+]i) and contraction in isolated rat myocytes. Rat model of MI was induced by subcutaneously injection of ISO (85 mg/kg) for 2 consecutive days. J-point elevation, heart rate, serum levels of creatine kinase (CK) and lactated dehydrogenase (LDH), and heart morphology changes were observed. Influences of TG on ICa-L, [Ca2+]i and contraction in isolated rat myocytes were observed by the patch-clamp technique and IonOptix detection system. TG significantly reduced J-point elevation, heart rate, serum levels of CK and LDH, and improved heart pathologic morphology. TG decreased ICa-L in concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of 31.65 μg/mL. TG (300 μg/mL) decreased ICa-L of normal and ischemic ventricular myocytes by 64.33 ± 1.28% and 61.29 ± 1.38% respectively. At 30 μg/mL, TG reduced Ca2+ transient by 21.67 ± 0.94% and cell shortening by 38.43 ± 6.49%. This study showed that TG displayed cardioprotective effects on ISO-induced MI rats and the underlying mechanisms may be related to inhibition of ICa-L, damping of [Ca2+]i and decrease of contractility.

• Authors: Xue Han, Mengying Li, Zhifeng Zhao, Yuanyuan Zhang, Jianping Zhang, Xuan Zhang, Ying Zhang, Shengjiang Guan, Li Chu
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 139 Issue 3 Pg. 240-248 (Mar 2019) ISSN: 1347-8648 [Electronic] Japan
• PMID: 30826245 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Calcium Channels, L-Type
• Cardiotonic Agents
• Ginsenosides
• Isoproterenol
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channels, L-Type (drug effects, metabolism)
• Cardiotonic Agents (pharmacology)
• Disease Models, Animal
• Ginsenosides (administration & dosage, pharmacology)
• Homeostasis (drug effects)
• Inhibitory Concentration 50
• Isoproterenol (toxicity)
• Male
• Myocardial Contraction (drug effects)
• Myocardial Ischemia (prevention & control)
• Myocytes, Cardiac (drug effects)
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley