title: A new flavonoid glycoside (APG) isolated from Clematis tangutica attenuates myocardial ischemia/reperfusion injury via activating PKCε signaling.
abstract: Clematis tangutica has been shown to be beneficial for the heart; however, the mechanism of this effectremains unknown. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new flavonoid glycoside isolated from Clematis tangutica. This study investigates the effects of APG on myocardial ischemia/reperfusion (IR) injury (IRI). An IRI model of primary myocardial cells and mice was used in this study. Compared with the IR group, APG preconditioning is protective against IRI in primary myocardial cells and in mice hearts in a dose-dependent manner. The cardioprotective mechanisms of APG may involve a significant PKCε translocation into the mitochondria and an activation of the Nrf2/HO-1 pathway, which respectively suppressesmitochondrial oxidative stress and inhibits apoptosis. In addition, PKCε-targeted siRNA and a PKCε specialized inhibitor (ε-V1-2) were used to inhibit PKCε expression and activity. The inhibition of PKCε reversed the cardioprotective effect of APG, with an inhibition of Nrf2/HO-1 activation and increased mitochondrial oxidative stress and cardiomyocyte apoptosis. In conclusion, PKCε activation plays an important role in the cardioprotective effects of APG. PKCε activation induced by APG preconditioning reduces mitochondrial oxidative stress and promotes Nrf2/HO-1-mediated anti-apoptosis signaling.
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China; Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, Jiangsu, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169, Changle West Road, Xi'an 710032, China; Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1, Xinsi Road, Xi'an 710038, China.
authors.forename: Shouyin
authors.initials: S
authors.lastname: Di
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: Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, 169, Changle West Road, Xi'an 710032, China.
authors.forename: Yingda
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, Jiangsu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, Jiangsu, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, Jiangsu, China.
authors.forename: Xinlong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
authors.forename: Juntian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Xi
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169, Changle West Road, Xi'an 710032, China.
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
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 Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, Jiangsu, China. Electronic address: yang200214yy@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China. Electronic address: aidongwenxijing@163.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002478:Cells, Cultured; D039324:Clematis / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D010936:Plant Extracts; C057792:apigetrin; D047310:Apigenin; D051744:Protein Kinase C-epsilon
keywords: Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside; Hemeoxygenase 1; Mitochondrial oxidative stress; Nuclear factor erythroid 2 p45 related factor 2; Protein kinase Cε