Planta Med 2004; 70(11): 1039-1044
DOI: 10.1055/s-2004-832644
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

A Study of the Cardioprotective Effect of Breviscapine During Hypoxia of Cardiomyocytes in vitro and During Myocardial Infarction in vivo

Xiao-Long Li1 , Ying-Qi Li1 , Wei-Min Yan1 , Hai-Yan Li1 , Hao Xu1 , Xiao-Xiang Zheng1 , Dian-Wu Guo2 , Li-Ke Tang2
  • 1Department of Biomedical Engineering, Zhejiang University (Yuquan Campus), Hangzhou, P. R. China
  • 2Hangzhou Minsheng Pharmaceutical Group Co., Ltd, China
Further Information

Publication History

Received: February 13, 2004

Accepted: June 26, 2004

Publication Date:
18 November 2004 (online)

Abstract

Breviscapine is a flavonoid extracted from Erigeron breviscapus. Hand.-Mazz, and it has been reported that breviscapine can activate K+ channels and block Ca2+ channels. In this paper, we studied the cardioprotective effects of breviscapine on electrocardiogram (ECG) changes (ST-segment elevation), infarction size in dog heart subjected to myocardial infarction caused by left coronary artery ligation and lactate dehydrogenase (LDH) leakage, changes of intracellular free Ca2+ levels, apoptosis and necrosis in cultured neonatal rat cardiomyocytes subjected to hypoxia. Additionally, the effect of breviscapine on myocardial oxygen consumption was detected in dog myocardium in vitro. The results showed that breviscapine treatment (1 mg/kg, 2 mg/kg and 4 mg/kg) significantly reduced ST-segment elevation and infarction size in hearts subjected to myocardial infarction, that breviscapine treatment (14.29 μg/mL, 28.57 μg/mL and 57.14 μg/mL) significantly decreased oxygen consumption in myocardium, and that breviscapine treatment (5 μg/mL, 10 μg/mL and 20 μg/mL) significantly reduced LDH leakage, intracellular free Ca2+ levels, apoptosis and necrosis in cardiomyocytes subjected to hypoxia. In conclusion, the present study indicates that breviscapine is in favor of myocardial protection.

Abbreviations

Brdu:bromodeoxyuridine

DMEM:Dulbecco’s modified Eagle’s medium

ECG:electrocardiogram

FITC:fluorescein isothiocyanate

LDH:lactate dehydrogenase

NBT:p-nitroblue tetrazolium chloride

PI:propidium iodide

PS:phosphatidylserine

ROI:regions of interests

References

  • 1 Zhang D -C, Jin J -Q, Liu X -J, Li J -C, Wang J -L. Chemical investigation on Erigeron breviscapus .  Chinese Traditional and Herbal Drugs. 1985;  16 408 [in Chinese]
  • 2 Wang L -J, Wang Y, Li J -M. Effect of breviscapine on delayed outward potassium current in single ventricular cell of guinea pig.  Chinese Pharmacological Bulletin. 2002;  18 326-8 [in Chinese]
  • 3 Wang L -J, Wang Y, Qiu L -P. Inhibition of breviscapine to calcium current in single ventricular cells of guinea pigs.  The Chinese Journal of Modern Applied Pharmacy. 2000;  17 272-4 [in Chinese]
  • 4 Liang B T, Gross G J. Direct preconditioning of cardiac myocytes via opioid receptors and KATP channels.  Circulation Research. 1999;  84 1396-1400
  • 5 Lazdunski M, Felin C, Vigne P. The sodium/hydrogen exchange system in cardiac cells: Its biochemical and pharmacological properties and its role in regulating internal concentration of sodium and internal pH.  Journal of Molecular and Cellular Cardiology. 1985;  17 1029
  • 6 Chan P, Hong C Y, Tomlinson B, Chang N C, Chen J P, Lee S T, Cheng J T. Myocardial protective effect of trilinolein: an antioxidant isolated from the medicinal plant Panax pseudoginseng .  Life Sciences. 1997;  61 1999-2006
  • 7 Schaper W, Frenzel H, Hort W. Experimental coronary artery occlusion. I. Measurement of infarct size.  Basic Research in Cardiology. 1979;  74 46-53
  • 8 Simpson P, Savin S. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells.  Circulation Research. 1982;  50 101-16
  • 9 Wroblewski F, LaDue J. Lactate dehydrogenase activity in blood.  Proceedings of the Society for Experimental Biology and Medicine. 1955;  90 210-3
  • 10 Vermes I, Haanen C, Steffens-Hakken H. et al . A novel assay for apoptosis: Flow cytometric detection of phosphatidylserine expression on early apoptosis cells using fluorescein labeled annexin V.  Journal of Immunological Methods. 1995;  184 39-51
  • 11 Al-Mehdi A B, Song C, Tozawa K, Fisher A B. Ca2+- and phosphatidylinositol 3-kinase-dependent nitric oxide generation in lung endothelial cells in situ with ischemia.  Journal of Biological Chemistry. 2000;  275 39 807-10
  • 12 Fan L L, Sun L H, Li J, Yue X H, Yu H X, Wang S Y, Dong S Q. Protective effect of puerarin against myocardial reperfusion injury: myocardial metabolism and ultrastructure.  Chinese Medical Journal. 1992;  105 451-6
  • 13 Keung W M, Lazo O, Kunze L, Vallee B L. Potentiation of the bioavailability of daidzin by an extract of Radix puerariae.  Proceedings of the Academy of Natural Sciences of Philadelphia.. 1996;  93 4284-8
  • 14 Mallat I, Tedgni A, Fontaliran F, Frank R, Durigon M, Fontaine G. Evidence of apoptosis in arrhythmogenic right ventricular dysplasia.  New England Journal of Medicine.. 1996;  355 1190-6
  • 15 Olivetli G, Quaini F, Sala R, Lagrasta C, Corradi D, Bonalina E, Gambert S R, Gigola E, Anversa P. Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart.  Journal of Molecular and Cellular Cardiology. 1995;  28 2005-16
  • 16 Yeh E TH. Life and death in the cardiovascular system.  Circulation. 1997;  95 782-6
  • 17 Fliss H, Gattinger D. Apoptosis in ischemic and reperfused rat myocardium.  Circulation Research. 1996;  79 949-6
  • 18 Brar B K, Stephanou A, Wagstaff M D, Coffin R S, Marber M S, Engelmann G, Latchman D S. Heat shock proteins delivered with a virus vector can protect cardiac cells against apoptosis as well as against thermal or ischaemic stress.  Journal of Molecular and Cellular Cardiology. 1999;  31 135-46
  • 19 Andree H A, Reutelinger C P, Hauptmann R, Hemker H C, Hermens W T, Willems G M. Binding of vascular anticoagulant alpha (VAC alpha) to planar phospholipid bilayers.  Journal of Biological Chemistry. 1990;  265 4923-8
  • 20 Steenbergen C, Perlman M, London R, Murphy E. Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart.  Circulation Research. 1990;  66 135-46
  • 21 Chen S J, Bradley M E, Lee T G. Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes: modulation by calcium-regulated proteases and protein kinases.  Molecular and Cellular Biochemistry. 1998;  178 141-9

Xiao-Xiang Zheng

Department of Biomedical Engineering

Zhejiang University

Yuquan Campus

Hangzhou 310027

P. R. China

Phone: +86-571-87951091

Fax: +86-571-87951676

Email: zxx@mail.bme.zju.edu.cn