Planta Med 2011; 77(7): 692-697
DOI: 10.1055/s-0030-1270920
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© Georg Thieme Verlag KG Stuttgart · New York

hERG Channel Inhibitors in Extracts of Coptidis Rhizoma

Anja Schramm1 [*] , Igor Baburin2 [*] , Steffen Hering2 , Matthias Hamburger1
  • 1Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
  • 2Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
Further Information

Publication History

received Nov. 19, 2010 revised February 11, 2011

accepted February 18, 2011

Publication Date:
16 March 2011 (online)

Abstract

Inhibition of the hERG channel delays repolarization and prolongs the QT interval and cardiac action potential which can lead to sudden death. Several drugs have been withdrawn from the market due to hERG channel inhibition. In the search of hERG channel inhibitors of natural origin, we established an HPLC-based profiling approach which combines HPLC-microfractionation and bioactivity testing on Xenopus laevis oocytes. The methanolic extract of the TCM herbal drug Coptidis rhizoma (Coptis chinensis Franch., Ranunculaceae) reduced the peak tail hERG current by 31.7 ± 2.0 % at 100 µg/mL. HPLC-based activity profiling pointed towards berberine as the active constituent. However, hERG inhibition by 100 µM of a reference sample of berberine (16.3 ± 1.6 %) was less pronounced than previously reported. Subsequent LC‐PDA‐MS analysis showed that berberine collected by microfractionation of the Coptis extract had been, in part, transformed to active dihydroberberine. Formic acid added to the HPLC mobile phase to reduce peak tailing of protoberberine alkaloids acted as a reducing reagent according to the mechanism of the Leuckart-Wallach reaction. Among other structurally related protoberberines tested, dihydroberberine (30.1 ± 10.1 % at 100 µM) was the most potent hERG inhibitor.

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1 The authors contributed equally to this work.

Prof. Dr. Matthias Hamburger

Department of Pharmaceutical Sciences
Division of Pharmaceutical Biology
University of Basel

Klingelbergstrasse 50

4056 Basel

Switzerland

Phone: +41 6 12 67 14 25

Fax: +41 6 12 67 14 74

Email: Matthias.Hamburger@unibas.ch