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  • Title: Inhibition of MEK/ERK/STAT3 signaling in oleuropein treatment inhibits myocardial ischemia/reperfusion.
    Author: Jin HX, Zhang YH, Guo RN, Zhao SN.
    Journal: Int J Mol Med; 2018 Aug; 42(2):1034-1043. PubMed ID: 29767261.
    Abstract:
    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‑α (TNF‑α), interleukin‑1β (IL‑1β), 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‑IκBα 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‑IκBα protein expression. TNF‑α, IL‑1β, IL‑6 and MDA were decreased; SOD, GSH and catalase levels inhibited TNF‑α, IL‑1β, 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‑IκBα protein expression, TNF‑α, IL‑1β, 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.
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