TY - JOUR A2 - ZaƂuski, Daniel AU - Zhang, Bin AU - Zhai, Mengen AU - Li, Buying AU - Liu, Zhenhua AU - Li, Kaifeng AU - Jiang, Liqing AU - Zhang, Meng AU - Yi, Wei AU - Yang, Jian AU - Yi, Dinghua AU - Liang, Hongliang AU - Jin, Zhenxiao AU - Duan, Weixun AU - Yu, Shiqiang PY - 2018 DA - 2018/02/20 TI - Honokiol Ameliorates Myocardial Ischemia/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway SP - 3159801 VL - 2018 AB - Reducing oxidative stress is a crucial therapeutic strategy for ameliorating diabetic myocardial ischemia/reperfusion (MI/R) injury. Honokiol (HKL) acts as an effective cardioprotective agent for its strong antioxidative activity. However, its roles and underlying mechanisms against MI/R injury in type 1 diabetes (T1D) remain unknown. Since SIRT1 and Nrf2 are pivotal regulators in diabetes mellitus patients suffering from MI/R injury, we hypothesized that HKL ameliorates diabetic MI/R injury via the SIRT1-Nrf2 signaling pathway. Streptozotocin-induced T1D rats and high-glucose-treated H9c2 cells were exposed to HKL, with or without administration of the SIRT1 inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA, and then subjected to I/R operation. We found that HKL markedly improved the postischemic cardiac function, decreased the infarct size, reduced the myocardial apoptosis, and diminished the reactive oxygen species generation. Intriguingly, HKL remarkably activated SIRT1 signaling, enhanced Nrf2 nuclear translocation, increased antioxidative signaling, and decreased apoptotic signaling. However, these effects were largely abolished by EX527 or SIRT1 siRNA. Additionally, our cellular experiments showed that Nrf2 siRNA blunted the cytoprotective effects of HKL, without affecting SIRT1 expression and activity. Collectively, these novel findings indicate that HKL abates MI/R injury in T1D by ameliorating myocardial oxidative damage and apoptosis via the SIRT1-Nrf2 signaling pathway. SN - 1942-0900 UR - https://doi.org/10.1155/2018/3159801 DO - 10.1155/2018/3159801 JF - Oxidative Medicine and Cellular Longevity PB - Hindawi KW - ER -