title: Cardioprotection by combination of three compounds from ShengMai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission.
abstract: GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index. Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3 activity, normalization of Bcl-2/Bax levels and improved mitochondrial function. Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated AMPKα phosphorylation. Interestingly, AMPK activation prevented hypoxia and reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions were significantly attenuated by knockdown of AMPKα. Collectively, these data show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission, thereby providing a rationale for future clinical applications and potential therapeutic strategy for MI/R injury.
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Fan
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Pang
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Ma
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Meijia
authors.initials: M
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P.R. China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D034242:Cyclooctanes / Q000008:administration & dosage; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D034281:Dynamins / Q000378:metabolism; D036145:Ginsenosides / Q000008:administration & dosage; D017705:Lignans / Q000008:administration & dosage; D008297:Male; D008813:Mice, Inbred ICR; D063154:Mitochondrial Dynamics / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011083:Polycyclic Compounds / Q000008:administration & dosage; D013150:Spirostans / Q000008:administration & dosage
chemical_list: D002316:Cardiotonic Agents; D034242:Cyclooctanes; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D017705:Lignans; D011083:Polycyclic Compounds; D013150:Spirostans; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; C442759:ginsenoside Rb1; C012541:ruscogenin; D055372:AMP-Activated Protein Kinases; C486391:Dnm1l protein, mouse; D034281:Dynamins; C011105:schizandrin