title: Paeonol and danshensu combination attenuates apoptosis in myocardial infarcted rats by inhibiting oxidative stress: Roles of Nrf2/HO-1 and PI3K/Akt pathway.
abstract: Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway.
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Lin-Rui
authors.initials: LR
authors.lastname: Duan
authors.affiliation: Department of Aerospace Physiology, School of Aerospace Medicine, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Sheng
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Xie
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Dong
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Bang-Le
authors.initials: BL
authors.lastname: Zhang
authors.affiliation: Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.|Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Si-Wang
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007545:Isoproterenol; D007773:Lactates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D019210:Troponin I / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism
chemical_list: D000098:Acetophenones; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D007773:Lactates; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D019210:Troponin I; D020107:Troponin T; C013638:paeonol; C035055:3,4-dihydroxyphenyllactic acid; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D052279:Creatine Kinase, MB Form; D007545:Isoproterenol