Analyzing the anti-ischemia–reperfusion injury effects of ginsenoside Rb1 mediated through the inhibition of p38α MAPK

Abstract

Recent studies have demonstrated that ginsenoside Rb1 protects the myocardium from ischemia-reperfusion (I/R) injury. However, the precise mechanisms for this protection have not been determined. This study aimed to determine whether the attenuation of I/R-induced myocardial injury by ginsenoside Rb1 (GS Rb1) is due to inhibition of p38α mitogen-activated protein kinase (MAPK). Sprague-Dawley rats were distributed among 6 treatment groups: sham group; I/R group; p38 MAPK inhibitor SB203580 group (SB + I/R); GS Rb1 group (GS + I/R); p38 MAPK agonist anisomycin group (Ani + I/R); and the GS Rb1 + Ani group (GS + Ani + I/R). All of the anaesthetized rats, except those in the sham group, underwent an open-chest procedure that involved 30 min of myocardial ischemia followed by 2 h of reperfusion. Myocardial infarction size (MIS), caspase-3 activity, and levels of the cytokine tumor necrosis factor alpha (TNF-α) in the myocardium were monitored. The expressions of p38α MAPK, caspase-3, and TNF-α in the myocardium were assayed. GS Rb1 reduced MIS and attenuated caspase-3 activity and the levels of TNF-α in the myocardium. Protein expression of total p38α MAPK was not significantly altered. In the Ani + I/R and I/R groups, the levels of phospho-p38α MAPK were significantly increased compared with the sham group, and these increased levels were reduced with GS Rb1. Hemodynamic parameters were not significantly different between the GS + I/R and SB + I/R groups. GS Rb1 exerts an anti-apoptotic effect that protects against I/R injury by inhibiting p38α MAPK phosphorylation, suggesting that GS Rb1-mediated protection requires the inhibition of p38α MAPK.

Inhibition of p38MAPK potentiates mesenchymal stem cell therapy against myocardial infarction injury in rats

“…Therefore, the expression or activation of TAK1 is an important indicator of the activity of the TGF-β-TAK1-p38MAPK signaling pathway. Several studies have suggested that the p38MAPK pathway is activated in the MI model (5,16) and p38MAPK has become a therapeutic target for heart diseases (17,18). However, other studies have demonstrated the pro-survival function of p38MAPK in MI (19,20).…”

“…Coronary atherosclerosis is elicited by a variety of endogenous and exogenous factors through different intracellular signaling pathways (4). MSC transplantation can promote angiogenesis in the infarct area to ameliorate cardiac function in MI (5). However, the clinical application of MSC transplantation is restricted by low survival rates of MSCs following transplantation (6).…”

The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

“…Moreover, MAPK participated in the regulation of cellular responses to a variety of stimuli, such as mitogens and pro-inflammatory cytokines. Mitogen-activated protein kinases 3, 8 and 14 regulate proliferation, gene expression, cell survival, apoptosis and many other cell functions ( Pearson et al, 2001 ; Li G. et al, 2015 ). The function mechanism of these important proteins might be that they influence the integral network instead of one target alone.…”

Role of ginsenosides, the main active components of Panax ginseng , in inflammatory responses and diseases

“…Cerebral IR injury is also ameliorated by G-Rb1 activating peroxisome proliferator-activated receptor-γ/heme oxygenase-1 (HO-1) or suppressing protease-activated receptor-1 expression in rat hippocampus [64] , [65] . Moreover, G-Rg1 shows a protective effect against cerebral IR injury by modulating the activation of p38 MAPK [66] . These results suggest that G-Rg1 has therapeutic potential for IR injury.…”