Zi-Kuan Wang1, Rui-Rui Chen1, Jing-Hua Li1, Jing-Yuan Chen2, Wei Li1, Xiao-Lin Niu1, Fang-Fang Wang1, Jing Wang1, Jing-Xiao Yang3. 1. Department of Cardiology, Tangdu Hospital, Air Force Medical University, Xi'an 710000, China. 2. Department of the Second Outpatient, Air Force 986 Hospital, Xi'an 710025, China. 3. Department of Cardiology, Tangdu Hospital, Air Force Medical University, Xi'an 710000, China. Electronic address: yangjingxiaowby@163.com.
Abstract
AIMS: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. MAIN METHODS: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway. RESULTS: Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1β, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation. CONCLUSION: Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.
AIMS: The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury. MAIN METHODS: C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway. RESULTS:Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1β, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation. CONCLUSION:Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.