Loganin protects against myocardial ischemia-reperfusion injury by modulating oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling

Abstract

BackgroundMyocardial ischemia-reperfusion injury (MIRI) is a pathological process that follows immediate revascularization of myocardial infarction and is characterized by exacerbation of cardiac injury. Loganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, can exert cardioprotective effects in cardiac hypertrophy and atherosclerosis. However, its role in ischemic heart disease remains largely unknown. MethodsConsidering that Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) has a protective effect on the heart, we developed a mouse model of MIRI to investigate the potential role of this pathway in loganin-induced cardioprotection. ResultsOur results showed that treatment with loganin (20 mg/kg) prevented the enlargement of myocardial infarction, myocyte destruction, serum markers of cardiac injury, and deterioration of cardiac function induced by MIRI. Myocardium subjected to I/R treatment exhibited higher levels of oxidative stress, as indicated by an increase in malondialdehyde (MDA) and dihydroethidium (DHE) density and a decrease in total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD), whereas treatment with loganin showed significant attenuation of I/R-induced oxidative stress. Loganin treatment also increased the expression of anti-apoptotic Bcl-2 and reduced the expression of caspase-3/9, Bax, and the number of TUNEL-positive cells in ischemic cardiac tissue. Moreover, treatment with loganin triggered JAK2/STAT3 phosphorylation, and AG490, a JAK2/STAT3 inhibitor, partially abrogated the cardioprotective effects of loganin, indicating the essential role of JAK2/STAT3 signaling in the cardioprotective effects of loganin. ConclusionsOur data demonstrate that loganin protects the heart from I/R injury by inhibiting I/R-induced oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.