(3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one attenuates cardiac dysfunction via the apelin/APJ signaling pathway

Abstract

Myocardial infarction (Mi) is associated with a high risk of mortality and is a major global health concern. The present study aimed to investigate the protective effects of (3r)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TiM) against Mi induced by isoproterenol (iSo) in a rat model and the underlying mechanisms. Wistar rats were assigned to 4 groups (n=10): The control group received saline treatment; the iSo group received an intraperitoneal injection of iSo (100 mg/kg); and the TiM (low) and TiM (high) groups received an intraperitoneal injection of iSo, plus a 1 and 2 mg/kg dose of TiM orally, respectively. TiM rats were treated with TiM daily for 12 days and received iSo injections on the final 2 days to induce MI. Cardiac function, apoptosis index and protein expression were subsequently determined. The levels of oxidative stress markers were determined by eliSas, whereas dna damage was detected using a cell death detection eliSa kit. Gene and protein expression were determined via reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. Following treatment with iSo, the maximum left ventricular contraction/relaxation velocity and left ventricular systolic pressure were significantly decreased, whereas the left ventricular end-diastolic pressure was increased; however, treatment with TIM significantly ameliorated ISO-induced cardiac dysfunction. Additionally, TIM treatment significantly decreased oxidative stress and inhibited the apoptosis of cardiomyocytes, as determined by a decrease in caspase activities, increased expression of B-cell lymphoma 2 (Bcl-2) and reduced expression of cleaved caspase-3, cleaved caspase-9 and Bcl-2-associated X. Furthermore, treatment with TiM upregulated the levels of apelin in the plasma and myocardium of iSo-treated rats. The results indicated that TiM protected cardiomyocytes against iSo-induced Mi, potentially via the apelin/apelin receptor signaling pathway. The results of the present study suggested that TiM may be a potential novel therapy for the treatment of Mi.