Ginsenoside‑Rb3 protects the myocardium from ischemia‑reperfusion injury via the inhibition of apoptosis in rats

Liu,Xiaomin; Jiang,Yichuan; Yu,Xiaofeng; Fu,Wenwen; Zhang,Hong; Sui,Dayun

doi:10.3892/etm.2014.2007

Ginsenoside‑Rb3 protects the myocardium from ischemia‑reperfusion injury via the inhibition of apoptosis in rats

Authors:
- Xiaomin Liu
- Yichuan Jiang
- Xiaofeng Yu
- Wenwen Fu
- Hong Zhang
- Dayun Sui
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Affiliations: Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: October 7, 2014 https://doi.org/10.3892/etm.2014.2007
Pages: 1751-1756

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Abstract

Ginsenoside‑Rb3 (G‑Rb3) has been previously demonstrated to attenuate myocardial ischemia‑reperfusion injury (MIRI). The aim of the present study was to investigate this further and determine whether G‑Rb3 protects the myocardium from ischemia‑reperfusion injury via the inhibition of apoptosis. Adult male Sprague Dawley rats were randomly divided into four groups: Sham, MIRI, G‑Rb3 treatment (orally, 20 mg/kg) and ischemic postconditioning (as the positive control). The drug or placebo treatment was administered to the rats once a day for three consecutive days, and MIRI was then induced by subjecting the rats to left anterior descending coronary artery ligation for 30 min and reperfusion for 2 h. The results showed that G‑Rb3 treatment significantly reduced the number of apoptotic cells in the myocardium and the expression of B‑cell lymphoma 2‑associated X protein, and increased the expression of B‑cell lymphoma 2. The activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase‑MB in the serum were also reduced significantly by the G‑Rb3 treatment. These findings suggest that G‑Rb3 inhibits apoptosis in the early stage of MIRI, and attenuates MIRI when the reperfusion continues. G‑Rb3 was also shown to significantly reduce the level of malondialdehyde and increase the activity of superoxide dismutase in the myocardium, which suggests that attenuating reactive oxygen species accumulation and oxidative stress may be the major mechanism underlying the anti‑apoptotic effects of G‑Rb3. The release of inflammatory factors was significantly attenuated by G‑Rb3, which may also be associated with its anti‑apoptotic effects.

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1	Chambless L, Keil U, Dobson A, et al: Population versus clinical view of case fatality from acute coronary heart disease: results from the WHO MONICA Project 1985–1990. Multinational MONItoring of Trends and Determinants in CArdiovascular Disease. Circulation. 96:3849–3859. 1997.PubMed/NCBI
2	Buja LM: Myocardial ischemia and reperfusion injury. Cardiovasc Pathol. 14:170–175. 2005. View Article : Google Scholar : PubMed/NCBI
3	Yellon DM and Hausenloy DJ: Myocardial reperfusion injury. N Engl J Med. 357:1121–1135. 2007. View Article : Google Scholar : PubMed/NCBI
4	Fliss H and Gattinger D: Apoptosis in ischemic and reperfused rat myocardium. Circ Res. 79:949–956. 1996. View Article : Google Scholar : PubMed/NCBI
5	Saraste A, Pulkki K, Kallajoki M, et al: Apoptosis in human acute myocardial infarction. Circulation. 95:320–323. 1997. View Article : Google Scholar : PubMed/NCBI
6	Haunstetter A and Izumo S: Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res. 82:1111–1129. 1998. View Article : Google Scholar : PubMed/NCBI
7	Xu H, Yu X, Qu S, Chen Y, Wang Z and Sui D: Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated from Panax quinquefolium, on permanent focal cerebral ischemic injury in rats. Exp Ther Med. 7:165–170. 2014.
8	Lin G, Yu X, Wang J, Qu S and Sui D: Beneficial effects of 20(S)-protopanaxadiol on antitumor activity and toxicity of cyclophosphamide in tumor-bearing mice. Exp Ther Med. 5:443–447. 2013.PubMed/NCBI
9	Wang LC and Lee TF: Effect of ginseng saponins on cold tolerance in young and elderly rats. Planta Med. 66:144–147. 2000. View Article : Google Scholar : PubMed/NCBI
10	Shin JY, Song JY, Yun YS, et al: Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function. Immunopharmacol Immunotoxicol. 24:469–482. 2002. View Article : Google Scholar : PubMed/NCBI
11	Nishijo H, Uwano T, Zhong YM and Ono T: Proof of the mysterious efficacy of ginseng: basic and clinical trials: effects of red ginseng on learning and memory deficits in an animal model of amnesia. J Pharmacol Sci. 95:145–152. 2004. View Article : Google Scholar : PubMed/NCBI
12	Li G and Wang Z, Sun Y, Liu K and Wang Z: Ginsenoside 20(S)-protopanaxadiol inhibits the proliferation and invasion of human fibrosarcoma HT1080 cells. Basic Clin Pharmacol Toxicol. 98:588–592. 2006. View Article : Google Scholar : PubMed/NCBI
13	Wang T, Yu X, Qu S, Xu H, Han B and Sui D: Effect of ginsenoside Rb3 on myocardial injury and heart function impairment induced by isoproterenol in rats. Eur J Pharmacol. 636:121–125. 2010. View Article : Google Scholar : PubMed/NCBI
14	Wang T, Yu XF, Qu SC, Xu HL and Sui DY: Ginsenoside Rb3 inhibits angiotensin II-induced vascular smooth muscle cells proliferation. Basic Clin Pharmacol Toxicol. 107:685–689. 2010. View Article : Google Scholar : PubMed/NCBI
15	Shi Y, Han B, Yu X, Qu S and Sui D: Ginsenoside Rb3 ameliorates myocardial ischemia-reperfusion injury in rats. Pharm Biol. 49:900–906. 2011. View Article : Google Scholar : PubMed/NCBI
16	Zhao ZQ, Corvera JS, Halkos ME, et al: Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 285:H579–H588. 2003.PubMed/NCBI
17	Nachlas MM and Shnitka TK: Macroscopic identification of early myocardial infarcts by alterations in dehydrogenase activity. Am J Pathol. 42:379–405. 1963.PubMed/NCBI
18	Gupta S: Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci. 69:2957–2964. 2001. View Article : Google Scholar : PubMed/NCBI
19	Werns SW and Lucchesi BR: Myocardial ischemia and reperfusion: the role of oxygen radicals in tissue injury. Cardiovasc Drugs Ther. 2:761–769. 1989. View Article : Google Scholar : PubMed/NCBI
20	Bolli R: Oxygen-derived free radicals and postischemic myocardial dysfunction (‘stunned myocardium’). J Am Coll Cardiol. 12:239–249. 1988.
21	Ren G, Dewald O and Frangogiannis NG: Inflammatory mechanisms in myocardial infarction. Curr Drug Targets Inflamm Allergy. 2:242–256. 2003. View Article : Google Scholar
22	Frangogiannis NG, Smith CW and Entman ML: The inflammatory response in myocardial infarction. Cardiovasc Res. 53:31–47. 2002. View Article : Google Scholar : PubMed/NCBI
23	Antonsson B: Bax and other pro-apoptotic Bcl-2 family ‘killer-proteins’ and their victim the mitochondrion. Cell Tissue Res. 306:347–361. 2001.
24	Budihardjo I, Oliver H, Lutter M, Luo X and Wang X: Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 15:269–290. 1999. View Article : Google Scholar : PubMed/NCBI