Stilbene derivatives as human 5-HT6 receptor antagonists from the root of Caragana sinica

Dong Hyuk Kim, Soon Hee Kim, Hyoung Ja Kim, Changbae Jin, Kwang Chul Chung, Hyewhon Rhim

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12 Citations (Scopus)

Abstract

The 5-HT6 receptor (5-HT6R) is a member of the class of recently discovered 5-hydroxytryptamine (5-HT) receptors. Due to the lack of selective 5-HT6R ligands, the cellular signaling mechanisms of the 5-HT6R are poorly understood. We previously developed a cell-based high-throughput screening (HTS) method for the 5- HT6R and screened synthetic chemical compounds. In the present study, we expanded our screening into natural products to find novel 5-HT6R ligands. We found that the ethyl acetate fraction from the root of Caragana sinica (537-18BE) produced the most potent antagonistic activity. After further isolation of 537-18BE, we found that three stilbene derivatives, (+)-α-viniferin, miyabenol C and pallidol, are active constituents of 537-18BE inhibiting the 5-HT6R. Among them, (+)-α-viniferin showed the most potent inhibition, and miyabenol C also produced a considerable inhibition. When examined effects on other neurotransmitters for selectivity, 537-18BE and three stilbene derivatives did not produce any notable effects on 5-HT4, 5-HT7, or muscarinic acetylcholine M1 (M1) receptors. Furthermore, 5-HT6R antagonistic effects of (+)-α-viniferin, miyabenol C and pallidol were confirmed on extracellular signal-regulated kinase 1 and 2 (ERK1/2) which exerts effects in downstream pathways of 5-HT6R activation.

Original languageEnglish
Pages (from-to)2024-2028
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume33
Issue number12
DOIs
Publication statusPublished - 2010 Dec 1

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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