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HPLC-based activity profiling for GABAA receptor modulators from the traditional Chinese herbal drug Kushen (Sophora flavescens root)

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Abstract

An EtOAc extract from the roots of Sophora flavescens (Kushen) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes transiently expressing GABAA receptors with subunit composition, α 1 β 2 γ 2S. HPLC-based activity profiling of the extract led to the identification of 8-lavandulyl flavonoids, kushenol I, sophoraflavanone G, (−)-kurarinone, and kuraridine as GABAA receptor modulators. In addition, a series of inactive structurally related flavonoids were characterized. Among these, kushenol Y (4) was identified as a new natural product. The 8-lavandulyl flavonoids are first representatives of a novel scaffold for the target.

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Abbreviations

TOFMS:

Time of flight mass spectrometry

PDA:

Photodiode array

HMBC:

Heteronuclear multiple-bond correlation

HSQC:

Heteronuclear single quantum coherence

CD:

Circular dichroism

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Authors and Affiliations

  1. Institute of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland

    Xinzhou Yang, Inken Plitzko & Matthias Hamburger

  2. Institute of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria

    Igor Baburin & Steffen Hering

Authors
  1. Xinzhou Yang
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  2. Igor Baburin
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  3. Inken Plitzko
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  4. Steffen Hering
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  5. Matthias Hamburger
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Corresponding author

Correspondence to Matthias Hamburger.

Additional information

Xinzhou Yang and Igor Baburin are equally contributed to this work.

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Yang, X., Baburin, I., Plitzko, I. et al. HPLC-based activity profiling for GABAA receptor modulators from the traditional Chinese herbal drug Kushen (Sophora flavescens root). Mol Divers 15, 361–372 (2011). https://doi.org/10.1007/s11030-010-9297-7

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