title: Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1.
abstract: Ischemia reperfusion (IR) injury (IRI) is associated with poor prognoses in the settings of both cardiac surgery and ischemic heart disease and causes mitochondrial oxidative stress and cell death. Silent information regulator 1 (SIRT1), a member of the histone deacetylase family, exerts anti-IRI effects. Bakuchiol (BAK), an analog of resveratrol and a monoterpene phenol isolated from the seeds of Psoralea corylifolia (Leguminosae), protects tissues from injury. This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of the pro-apoptotic protein Bax, and decreases in the cleaved Caspase 3 level). However, Sirtinol and SIRT1 siRNA each blocked BAK-induced cardioprotection by inhibiting SIRT1 signaling. Additionally, BAK significantly increased the activities of mitochondrial succinate dehydrogenase, cytochrome c oxidase, and mitochondrial superoxide dismutase and decreased the production of malondialdehyde. These findings suggested that BAK significantly attenuated IR-induced mitochondrial oxidative damage. However, Sirtinol and SIRT1 siRNA abolished BAK-dependent mitochondrial function. In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT1/PGC-1α signaling.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.|Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, China.|Department of Cardiothoracic Surgery, The 94th Hospital of Chinese PLA, 1028 Jingangshan Road, Nanchang, 330000, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Bodong
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Central Hospital of Xi'an, 185 Houzaimen Road, Xi'an, 710033, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China. jianjunxu888@126.com.|Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, China. jianjunxu888@126.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China. zhenxiaojin210@126.com.
authors.forename: Zhenxiao
authors.initials: Z
authors.lastname: Jin
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D010636:Phenols / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016277:Ventricular Function, Left
chemical_list: D051017:Apoptosis Regulatory Proteins; D001549:Benzamides; D009284:Naphthols; D010636:Phenols; C439060:sirtinol; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form; D056564:Sirtuin 1; C012765:bakuchiol
keywords: Bakuchiol; Ischemia reperfusion injury; Mitochondrial oxidative damage; Silent information regulator 1