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Planta Med 2010; 76(6): 572-582
DOI: 10.1055/s-0029-1240602
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Cardiac and Electrophysiological Effects of Primary and Refined Extracts from Leonurus cardiaca L. (Ph.Eur.)

Malte Ritter1 [*] , Kerstin Melichar1 [*] , Sabine Strahler2 , Kenny Kuchta2 , Jan Schulte1 , Laura Sartiani3 , Elisabetta Cerbai3 , Alessandro Mugelli3 , Friedrich-Wilhelm Mohr1 , Hans Wilhelm Rauwald2 , Stefan Dhein1
  • 1Clinic for Cardiac Surgery, University of Leipzig, Leipzig, Germany
  • 2Department of Pharmaceutical Biology, University of Leipzig, Leipzig, Germany
  • 3Department of Pharmacology, University of Florence, Florence, Italy
Further Information

Publication History

received June 9, 2009 revised October 14, 2009

accepted October 18, 2009

Publication Date:
16 November 2009 (online)

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Erratum for: Cardiac and Electrophysiological Effects of Primary and Refined Extracts from Leonurus cardiaca L. (Ph.Eur.)Planta Med 2010; 76(06): E11-E11
DOI: 10.1055/s-0029-1240698

Abstract

Although several antiarrhythmic drugs of chemical origin are in clinical use since decades, their application is often limited by their adverse effects and especially by their inherited proarrhythmic risk, which can lead to a significantly increased mortality in patients receiving these compounds. On the other hand, aqueous extracts from the aerial parts of the European Lamiaceae Leonurus cardiaca (Ph.Eur.) have been used for centuries as a remedy against tachyarrhythmia and other cardiac disorders. Nevertheless, a scientific basis for the claim of direct cardiac electrophysiological, antiarrhythmic, or functional effects of Leonurus cardiacae herba (LCH) preparations has not been established until now. In order to enrich the active constituents from the primary extract which was tested as the most cardioactive, namely the aqueous Soxhlet extract, and to eliminate undesired substances such as the dichloromethanic fraction or potassium, a bioassay guided fractionation procedure was applied, resulting in the development of a Leonurus cardiaca refined extract (LCRE) which was characterised together with Leonurus crude extracts by a newly developed gradient elution HPLC fingerprint analysis for separation and quantification of six major phenolics as well as by qNMR for determining the stachydrine content. This refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased. In addition, voltage-clamp measurements were performed on the following cell models in order to characterise the electrophysiological profile of LCRE: neonatal rat ventricular cardiomyocytes to investigate the effect on INa and ICa.L, sinoatrial node cells and ventricular myocytes isolated from adult guinea pigs to test effects on If and action potential (AP) duration, as well as HERG-transfected HEK 293 cells to analyse the influence on the IK.r. In these voltage clamp experiments LCRE exerted a calcium-antagonistic activity by ICa.L blockade, reduced the repolarising current IK.r, and prolonged the AP-duration, while INa was not affected. Although LCRE displayed only weak effects on the If amplitude and voltage dependence, it significantly prolonged the activation time constant of If. Thus, LCRE acts on multiple electrophysiological targets, specifically ICa.L, IK.r, and If, observed both at whole organ and single cell level.

Key words

Leonurus cardiaca - Lamiaceae - refined extract - plant analysis - antianginal and antiarrhythmic effects - voltage clamp - epicardial mapping

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1 These two authors contributed equally.

Prof. Dr. Stefan Dhein

Clinic for Cardiac Surgery
University of Leipzig

Struempellstrasse 39

04289 Leipzig

Germany

Phone: + 49 34 18 65 16 51

Fax: + 49 34 18 65 14 52

Email: dhes@medizin.uni-leipzig.de

Prof. Dr. Hans Wilhelm Rauwald

Chair of Pharmaceutical Biology
University of Leipzig

Johannisallee 21–23

04103 Leipzig

Germany

Phone: + 49 34 19 73 69 51

Fax: + 49 34 59 73 69 59

Email: rauwald@rz.uni-leipzig.de