Inhibition of MEK/ERK/STAT3 signaling in oleuropein treatment inhibits myocardial ischemia/reperfusion

Studies have shown that oleuropein has antifungal, anti-inflammatory, antiviral, antioxidant, anticancer and hypoglycemic functions. TTC solution staining was used to measure myocardial infarction size. A commercial kit was used to measure lactate dehydrogenase (LDH), creatinine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL 6, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase levels. Western blot analysis was used to measure p53, p-MEK p-ERK and p-I kappa B alpha protein expression. The present study reports that the protective effect of oleuropein also prevents against myocardial ischemia/reperfusion (myocardial I/R). The aim of this retrospective study was to evaluate this protective effect of oleuropein and the mechanisms by which myocardial I/R is prevented. Oleuropein inhibited myocardial infarction size, CK-MB and LDH serum levels in a myocardial I/R rat model. Moreover, oleuropein also attenuated caspase-3 activity, and p53, phosphorylated (p)-mitogen-activated protein kinase kinase (MEK), p-extracellular signal-regulated protein kinase (ERK) and p-I kappa B alpha protein expression. TNF-alpha, IL-1 beta, IL-6 and MDA were decreased; SOD, GSH and catalase levels inhibited TNF-alpha, IL-1 beta, IL-6 and MDA levels, and increased SOD, GSH and catalase levels in myocardial I/R rats treated with oleuropein. Rats orally administered the MEK inhibitor PD0325901, in addition to oleuropein, exhibited inhibited myocardial infarction size, CK-MB and LDH serum levels compared with rats treated with oleuropein only. Rats treated with MEK inhibitor also exhibited suppressed caspase-3 activity, p53, p-MEK p-ERK and p-I kappa B alpha protein expression, TNF-alpha, IL-1 beta, IL-6, SOD, GSH, MDA and catalase levels, and induced p-signal transducer and activator of transcription 3 (STAT3) protein expression compared with rats treated with oleuropein only. Taken together, these results suggest that MEK/ERK/STAT3 signaling regulates the inhibition of myocardial I/R in rats treated with oleuropein.