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Planta Med 2013; 79(14): 1289-1297
DOI: 10.1055/s-0033-1350671
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Clematichinenoside Attenuates Myocardial Infarction in Ischemia/Reperfusion Injury both In Vivo and In Vitro

Rui Zhang   *
1   State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Weirong Fang   *
1   State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Dan Han
1   State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Lan Sha
1   State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Jie Wei
1   State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Lifang Liu
2   Department of Pharmacognosy and the Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, P. R. China
,
Yunman Li
1   State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
› Author Affiliations
Further Information

Publication History

received 08 June 2013
revised 28 June 2013

accepted 05 July 2013

Publication Date:
08 August 2013 (online)

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Abstract

Clematichinenoside is a triterpenoid saponin isolated from the roots of Clematis chinensis. Oxidative stress and excessive nitric oxide production are thought to play considerable roles in ischemia/reperfusion injury that impairs cardiac function. The present study investigated the protective effect of clematichinenoside on regional and global ischemia/reperfusion injury and ventricular myocytes. In vivo, regional myocardial ischemia/reperfusion injury of rats was induced by the occlusion of the left anterior descending coronary artery, and isolated guinea pigs heart using Langendorff apparatus served as a global ischemia/reperfusion injury model ex vivo. Primary cultured neonatal ventricular myocytes were further applied to explore the anti-ischemia/reperfusion injury property in vitro. Infarct size was measured with TTC stain; enzyme activities such as lactate dehydrogenase, creatine kinase, superoxide dismutase, malondialdehyde, and nitric oxide were analyzed with assay kits; inducible nitric oxide synthase and endothelial nitric oxide synthase expressions were determined by Western blot. Clematichinenoside attenuated infarct size, decreased lactate dehydrogenase, creatine kinase, and malondialdehyde levels and enhanced superoxide dismutase activity. Clematichinenoside improved hemodynamics indexes, such as left ventricular developed pressure, maximum left ventricular developed pressure, and increase/decrease rate (± dp/dtmax) in the isolated guinea pig heart after reperfusion. Clematichinenoside also inhibited excessive production of nitric oxide through downregulating inducible nitric oxide synthase as well as upregulating endothelial nitric oxide synthase during ischemia/reperfusion injury. Clematichinenoside attenuates ischemia/reperfusion injury in vivo, ex vivo, and in vitro via an antioxidant effect and by restoring the balance between inducible nitric oxide synthase and endothelial nitric oxide synthase.

Key words

clematichinenoside - myocardial ischemia/reperfusion - ventricular myocytes - oxidative stress - nitric oxide - Clematis chinensis - Ranunculaceae

* These two authors contributed equally to this work.


 

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