Effect of 20 (S)-protopanaxatriol and its epimeric derivatives on myocardial injury induced by isoproterenol

Abstract

Objective: It was reported Panax ginseng had diverse components and multifaceted pharmacological functions. This study aims to investigate the effect of 20 (S)-protopanaxatriol (PT, CAS 179799-20-3) and its epimeric derivatives (20S, 24R-epoxy-dammarane-3β, 6α, 12β, 25-tetraol, PTD1 and 20S, 24S-epoxy-dammarane-3β, 6α, 12β, 25-tetraol, PTD2) on myocardial injury induced by isoproterenol in rats.

Methods: Male Wistar rats were administered orally 20 (S)-protopanaxatriol or its epimeric derivatives for 7 days. Four days after treatment, all rats, except those in the control group, were subcutaneously injected with isoproterenol (20 mg/kg) for 3 consecutive days. Two hours after the last isoproterenol injection, the rats were anaesthetized and sacrificed. The biochemical parameters were assayed and pathological examination of the heart tissues was performed.

Results: Administration of PT and PTD1 resulted in a reduction in creatine kinase and lactate dehydrogenase. PT and PTD1 inhibited not only the elevation of malondialdehyde content, but also the reduction of superoxide dismutase activity, glutathione peroxidase and total antioxidant capacity. The pathohistological changes induced by isoproterenol were also ameliorated by PT and PTD1.

Conclusion: The present findings suggest that PT and PTD1 exerted cardioprotective effects against myocardial ischemic injury by enhancing the anti-free-radical actions of heart tissues. Furthermore the results indicated that the configuration of C-24 of the funan ring was involved in the pharmacological action of the epimeric derivatives of 20(S)-protopanaxatriol.

Key words

CAS 179799-20-3 - Isoproterenol - Myocardial ischemia - Panax ginseng - Protopanaxatriol

• References

• 1 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999; 58: 1685-93
• 2 Xie JT, Shao ZH, Vanden Hoek TL, Chang WT, Li J, Mehendale S et al. Antioxidant effects of ginsenoside Re in cardiomyocytes. Eur J Pharmacol. 2006; 532: 201-7
• 3 Kwok HH, Ng WY, Yang MS, Mak NK, Wong RN, Yue PY. The ginsenoside protopanaxatriol protects endothelial cells from hydrogen peroxide-induced cell injury and cell death by modulating intracellular redox status. Free Radic Biol Med. 2010; 48: 437-45
• 4 Yu C, Fu F, Yu X, Han B, Zhu M. Cardioprotective effect of ocotillol, a derivate of pseudoginsenoside F11, on myocardial injury induced by isoproterenol in rats. Arzneimittelforschung. 2007; 57: 568-72
• 5 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193: 265-75
• 6 Karthick M, Stanely Mainzen Prince P. Preventive effect of rutin, a bioflavonoid, on lipid peroxides and antioxidants in isoproterenol-induced myocardial infarction in rats. J Pharm Pharmacol. 2006; 58: 701-7
• 7 Remiao F, Carmo H, Carvalho F, Bastos ML. Copper enhances isoproterenol toxicity in isolated rat cardiomyocytes: effects on oxidative stress. Cardiovasc Toxicol. 2001; 1: 195-204
• 8 Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans. 2007; 35: 1147-50
• 9 Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS. Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol. 2002; 34: 379-88
• 10 Lewis SE, Boyle PM, McKinney KA, Young IS, Thompson W. Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril. 1995; 64: 868-70