Honokiol Ameliorates Myocardial Ischemia/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway.

Abstract

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.

• Authors: Bin Zhang, Mengen Zhai, Buying Li, Zhenhua Liu, Kaifeng Li, Liqing Jiang, Meng Zhang, Wei Yi, Jian Yang, Dinghua Yi, Hongliang Liang, Zhenxiao Jin, Weixun Duan, Shiqiang Yu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2018 Pg. 3159801 ( 2018) ISSN: 1942-0994 [Electronic] United States
• PMID: 29675132 (Publication Type: Journal Article)

Chemical References

• Biphenyl Compounds
• Lignans
• NF-E2-Related Factor 2
• honokiol
• Superoxide Dismutase
• Sirtuin 1

Topics

• Animals
• Apoptosis (drug effects)
• Biphenyl Compounds (therapeutic use)
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Echocardiography
• In Situ Nick-End Labeling
• Lignans (therapeutic use)
• Myocardial Reperfusion Injury (drug therapy, genetics, metabolism)
• Myocardium (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Oxidative Stress (drug effects)
• Rats
• Signal Transduction (drug effects)
• Sirtuin 1 (genetics, metabolism)
• Superoxide Dismutase (genetics, metabolism)