Combination of the ginsenosides Rb3 and Rb2 exerts protective effects against myocardial ischemia reperfusion injury in rats

Abstract

Ginsenoside Rb3 (G-Rb3) has been demonstrated to alleviate myocardial ischemia reperfusion injury (MIRI); however, it is difficult to separate G-Rb2 from its isomer G-Rb3. The current study aimed to compare the cardioprotective effects of G-Rb3 and the concomitant use of G-Rb3 and G-Rb2 (G-Rb3/Rb2) on MIRI in rats. A rat model of MIRI was established by ligation of the left anterior descending coronary artery and the rats were randomly divided into five groups. Prior to MIRI, G-Rb3/Rb2 (20 mg/kg), G-Rb3 (20 mg/kg) and diltiazem (DLZ; 20 mg/kg, as a positive control) were orally administered to the rats once a day for 3 consecutive days. After 30 min of ischemia and 120 min of reperfusion, cardiac function, infarct size, cardiac marker enzymes, antioxidative parameters, inflammatory factors, histopathological changes, cardiomyocyte apoptosis, and B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein and caspase-3 expression were determined using a multi-channel physiological recording system, nitrotetrazolium blue chloride, biochemical kits, radioimmunoassay kits, hematoxylin and eosin, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay, immunohistochemistry and reverse transcription-quantitative PCR, respectively. The results indicated that treatment with G-Rb3/Rb2 significantly protected rats against MIRI, as shown by improved cardiac function, reduced myocardial ischemic area, decreased serum activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase MB, decreased serum concentrations of interleukin-6 and tumor necrosis factor-α, decreased malondialdehyde concentration in myocardial tissues, increased activities of superoxide dismutase, glutathione peroxidase and catalase in myocardial tissues, reduced histopathological changes in myocardial tissues, reduced number of apoptotic cardiomyocytes, and changes in the expression levels of caspase-3, Bcl-2 and Bax. In addition, the effects of treatment with G-Rb3/Rb2, G-Rb3 or DLZ were equivalent. The protective effects of G-Rb3/Rb2 on MIRI were similar to those of G-Rb3 in terms of oxidative stress, inflammatory factors and inhibition of cardiomyocyte apoptosis. Therefore, G-Rb3/Rb2 may be developed as a concomitant treatment for MIRI.

Baicalin Prevents Myocardial Ischemia/Reperfusion Injury Through Inhibiting ACSL4 Mediated Ferroptosis

“…Diltiazem was purchased from Tianjin Tianyu Pharmaceutical Co., Ltd. (Tianjin, China). Diltiazem (20 mg/kg), a specific L-type calcium channel blocker, was selected as positive control based on previous studies (Zhu et al, 2015;Liu et al, 2020). It has been widely used in the treatment of ischemic heart disease and hypertension (Moukarbel et al, 2004;Liu et al, 2020).…”

“…Diltiazem (20 mg/kg), a specific L-type calcium channel blocker, was selected as positive control based on previous studies (Zhu et al, 2015;Liu et al, 2020). It has been widely used in the treatment of ischemic heart disease and hypertension (Moukarbel et al, 2004;Liu et al, 2020). Beneficial effects such as infarct size reduction and myocardial performance improvement have been reported following diltiazem treatment (Moukarbel et al, 2004).…”

Ginsenoside Re Improves Inflammation and Fibrosis in Hepatic Tissue by Upregulating PPARγ Expression and Inhibiting Oxidative Stress in db/db Mice

“…Our group is currently undertaking a long-term study assessing the effects of various ginsenosides, including Re, in various animal models of chronic disease, such as hypertension [3,4], CHD [5][6][7], and T2DM. Especially, we had demonstrated that Re improves acute myocardial ischemiamediated myocardial injury, myocardial fibrosis, and heart failure.…”

20(S)-Protopanaxadiol Alleviates Myocardial Ischemia/Reperfusion Injury in Rats Through Suppression of Oxidative Stress and Apoptosis

“…Our previous studies has showed that protopanaxadioltype ginsenosides exert significant cardioprotective effects. 6,9,10 In this study, PPD as the active metabolite of protopanaxadioltype ginsenosides significantly attenuated I/R-induced myocardial infarction and improved left ventricular function with decreased LVIDs, LVIDd, and increased EF%, FS%. Elevation of cardiac enzyme, including AST, LDH, and CKMB, indicated the presence of myocardial injury.…”

“…6,7 Furthermore, the cardioprotective effects of Rb1, Rb2 and Rb3 were proved by our studies. [8][9][10] But as the active metabolite of these ginsenosides, the effects on myocardial ischemia-reperfusion injury of PPD are still unclear.…”