HPLC-based Activity Profiling – Discovery of Sanggenons as GABAA Receptor Modulators in the Traditional Chinese Drug Sang bai pi (Morus alba Root Bark)

Hyun Jung Kim; Igor Baburin; Janine Zaugg; Samad Nejad Ebrahimi; Steffen Hering; Matthias Hamburger

doi:10.1055/s-0031-1298229

Planta Medica, Inhaltsverzeichnis

Planta Med 2012; 78(5): 440-447
DOI: 10.1055/s-0031-1298229

Biological and Pharmacological Activity

Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

HPLC-based Activity Profiling – Discovery of Sanggenons as GABA_A Receptor Modulators in the Traditional Chinese Drug Sang bai pi (Morus alba Root Bark)

Hyun Jung Kim¹ [*] , Igor Baburin² [*] , Janine Zaugg¹ , Samad Nejad Ebrahimi¹ ^, ³ , Steffen Hering² , Matthias Hamburger¹

¹Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
²Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
³Department of Phytochemistry, Medicinal Plant and Drugs Research Institute, Shahid Beheshti University, G. C., Tehran, Iran

Abstract

EtOAc extracts from two batches of Morus alba root bark (Sang bai pi) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes, which transiently expressed GABA_A receptors of the subunit composition α ₁ β ₂ γ _2S. With the aid of HPLC-based activity profiling of the extract from the first batch, activity was traced to a peak subsequently identified as sanggenon G (3). The second batch had a different phytochemical profile, and HPLC-based activity profiling led to the identification of sanggenon C (4) and a stereoisomer of sanggenon D (2) as positive GABA_A receptor modulators. The structurally related compound kuwanon L (1) was inactive. The sanggenons represent a new scaffold of positive GABA_A receptor modulators.

Key words

GABA_A receptor modulator - Xenopus oocytes - HPLC-based activity profiling - sanggenon - Morus alba - Moraceae

Volltext

Referenzen

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1 These authors contributed equally to this work.

Prof. Matthias Hamburger

Department of Pharmaceutical Sciences
University of Basel

Klingelbergstrasse 50

4056 Basel

Switzerland

Telefon: +41 (0) 6 12 67 14 25

Fax: +41 (0) 6 12 67 14 74

eMail: matthias.hamburger@unibas.ch

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