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Biochim Biophys Acta Mol Basis Dis. 2017 Mar;1863(3):701-711. doi: 10.1016/j.bbadis.2016.12.013. Epub 2016 Dec 24.

A new flavonoid glycoside (APG) isolated from Clematis tangutica attenuates myocardial ischemia/reperfusion injury via activating PKCε signaling.

Author information

1
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.
2
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.
3
Department of Biomedical Engineering, The Fourth Military Medical University, 169, Changle West Road, Xi'an 710032, China.
4
Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, 169, Changle West Road, Xi'an 710032, China.
5
Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, Jiangsu, China.
6
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China.
7
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1, Xinsi Road, Xi'an 710038, China.
8
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.
9
Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127, Changle West Road, Xi'an 710032, China. Electronic address: aidongwenxijing@163.com.

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.

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

PMID:
28024940
DOI:
10.1016/j.bbadis.2016.12.013
[Indexed for MEDLINE]
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