Gypenoside A protects ischemia/reperfusion injuries by suppressing miR-143-3p level via the activation of AMPK/Foxo1 pathway.

Abstract

Ischemia-reperfusion (I/R) injury is a major side effect associated with coronary heart disease (CHD). Gypenoside A (GP) is one of the dominant active components of Gynostemma pentaphyllum and has the potential to attenuate myocardial I/R injuries. The major purpose of this study was to explore the mechanism driving the protective effect of GP on myocardial tissue by focusing on the interaction between GP and miR-143-3p. Cardiomyocytes were pre-treated with GP and subjected to oxygen-glucose deprivation/re-oxygenation (OGD/R). Changes in cell viability, apoptosis, and expression levels of factors involved in the adenosine monophosphate activated protein kinase (AMPK)/Foxo1-mediated miR-143-3p pathway were detected. The levels of AMPK and miR-143-3p were then modulated using an inhibitor and a mimic, respectively, to confirm their central roles in the effect of GP. The administration of GP attenuated OGD/R-induced injuries by increasing cell viability and suppressing apoptosis, which was associated with the activation of AMPK/Foxo1 signaling and the decreased level of miR-143-3p. The down-regulation of AMPK and up-regulation of miR-143-3p both counteracted the function of GP on cardiomyocytes. The role of miR-143-3p suppression in the anti-I/R effect of GP was also verified with rat model. The injection of miR-143-3p agomir inhibited the cardio-protective effect of GP in a manner similar to that in the in vitro assays. Our results confirm the cardio-protective effect of GP, which is exerted by suppressing the level of miR-143-3p via the activation of AMPK signaling.