title: YiXin-Shu, a ShengMai-San-based traditional Chinese medicine formula, attenuates myocardial ischemia/reperfusion injury by suppressing mitochondrial mediated apoptosis and upregulating liver-X-receptor α.
abstract: Positive evidence from clinical trials has fueled growing acceptance of traditional Chinese medicine (TCM) for the treatment of cardiac diseases; however, little is known about the underlying mechanisms. Here, we investigated the nature and underlying mechanisms of the effects of YiXin-Shu (YXS), an antioxidant-enriched TCM formula, on myocardial ischemia/reperfusion (MI/R) injury. YXS pretreatment significantly reduced infarct size and improved viable myocardium metabolism and cardiac function in hypercholesterolemic mice. Mechanistically, YXS attenuated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway (as reflected by inhibition of mitochondrial swelling, cytochrome c release and caspase-9 activity, and normalization of Bcl-2 and Bax levels) without altering the death receptor and endoplasmic reticulum-stress death pathways. Moreover, YXS reduced oxidative/nitrative stress (as reflected by decreased superoxide and nitrotyrosine content and normalized pro- and anti-oxidant enzyme levels). Interestingly, YXS upregulated endogenous nuclear receptors including LXRα, PPARα, PPARβ and ERα, and in-vivo knockdown of cardiac-specific LXRα significantly blunted the cardio-protective effects of YXS. Collectively, these data show that YXS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and oxidative stress and by upregulating LXRα, thereby providing a rationale for future clinical trials and clinical applications.
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Longwei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Lingchen
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Song
authors.initials: S
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Ben
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. 160 PuJian Road, Shanghai 200127, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Pu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000096:biosynthesis; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D000071518:Liver X Receptors / Q000096:biosynthesis* / Q000235:genetics; D008516:Medicine, Chinese Traditional; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D000071518:Liver X Receptors; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D053453:Caspase 9