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.