title: Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1.
abstract: Berberine (BBR) exerts potential protective effect against myocardial ischemia/reperfusion (MI/R) injury. Activation of silent information regulator 1 (SIRT1) signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl) and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91(phox) expression, malondialdehyde (MDA) level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD) level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Yu
authors.affiliation: Beijing Aortic Disease Center, Anzhen Hospital, Capital Medical University, Beijing 100029, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhenxiao
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Weixun
authors.initials: W
authors.lastname: Duan
authors.affiliation: School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Guolong
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Mengen
authors.initials: M
authors.lastname: Zhai
authors.affiliation: College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Dinghua
authors.initials: D
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006334:Heart Function Tests / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009284:Naphthols; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D001549:Benzamides; D001599:Berberine; D053148:Caspase 3; D003402:Creatine Kinase; D051858:Forkhead Transcription Factors; D007770:L-Lactate Dehydrogenase; D009284:Naphthols; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D056564:Sirtuin 1; D051028:bcl-2-Associated X Protein; C439060:sirtinol; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1