Planta Med 2015; 81(12/13): 1103-1110
DOI: 10.1055/s-0035-1546234
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

GABAA Receptor Binding Assays of Standardized Leonurus cardiaca and Leonurus japonicus Extracts as Well as Their Isolated Constituents[*]

Hans Wilhelm Rauwald
1   Department of Pharmaceutical Biology, Leipzig University, Leipzig, Germany
Alex Savtschenko
1   Department of Pharmaceutical Biology, Leipzig University, Leipzig, Germany
Alexander Merten
1   Department of Pharmaceutical Biology, Leipzig University, Leipzig, Germany
Christian Rusch
1   Department of Pharmaceutical Biology, Leipzig University, Leipzig, Germany
Kurt Appel
2   VivaCell Biotechnology, Denzlingen, Germany
Kenny Kuchta
3   National Institute of Health Sciences, Division of Pharmacognosy, Phytochemistry and Narcotics, Setagaya-ku, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

received 20 March 2015
revised 22 May 2015

accepted 25 May 2015

Publication Date:
28 July 2015 (online)


A main traditional use of European Leonurus cardiaca and East Asian Leonurus japonicus is in the treatment of neurological disorders such as anxiety, depression, nervousness, and as a sedative for insomnia. However, their mechanism of action is still under discussion. As anxiety and depressive disorders are increasingly being recognized as connected to dysfunctions of the gamma-aminobutyric acid system, the in vitro effects of standardized L. cardiaca and L japonicus extracts as well as five of their isolated constituents, namely, the labdane-type isoleosibirin, the novel iridoid 7R-chloro-6-desoxy-harpagide, the phenylethanoid lavandulifolioside, and the N-containing compounds stachydrine and leonurine, on this type of neuronal receptor were investigated for the first time. Extracts of L. cardiaca and L. japonicus, characterized by reversed-phase high-performance liquid chromatography determination, as well as their above named isolated, possible active constituents of different chemical nature were tested in several receptor binding assays at rat GABAA receptors using [3H]-SR95 531 and [3H]-Ro-15–1788 (flumazenil)/diazepam control. The L. cardiaca and L. japonicus extracts as well as leonurine inhibited the concentration-dependent binding of [3H]-SR95 531 to the gamma-aminobutyric acid site of the gamma-aminobutyric acid type A receptor with a high binding affinity: IC50s 21 µg/ml, 46 µg/ml, and 15 µg/ml, respectively. In contrast, binding to the benzodiazepine site of the rat gamma-aminobutyric acid type A receptor had a 15 to 30 times lower binding affinity than to the gamma-aminobutyric acid site. The presented experiments provide hints that the neurological mechanism of action of L. cardiaca and L. japonicus may essentially be based on their interaction to the gamma-aminobutyric acid site of the gamma-aminobutyric acid type A receptor, while the benzodiazepine site most probably does not contribute to this effect. In the case of L. japonicus, these effects can be at least partially explained by its leonurine constituent, whereas the active principle of L. cardiaca, which does not contain leonurine, is subject to further research as none of the other investigated individual constituents displayed significant activity in the applied test system.

* Dedicated to Prof. Dr. Drs. h. c. Adolf Nahrstedt, Münster, on the occasion of his 75th birthday. His earlier report [1] was an essential inspiration for the research project presented in the paper at hand.

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