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

Research output: Contribution to journalArticle

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

Fingerprint

Caragana
Stilbenes
High-Throughput Screening Assays
Ligands
Mitogen-Activated Protein Kinase 3
Serotonin Receptors
Mitogen-Activated Protein Kinase 1
serotonin 6 receptor
Biological Products
Cholinergic Agents
Acetylcholine
Neurotransmitter Agents

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Kim, Dong Hyuk ; Kim, Soon Hee ; Kim, Hyoung Ja ; Jin, Changbae ; Chung, Kwang Chul ; Rhim, Hyewhon. / Stilbene derivatives as human 5-HT6 receptor antagonists from the root of Caragana sinica. In: Biological and Pharmaceutical Bulletin. 2010 ; Vol. 33, No. 12. pp. 2024-2028.
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Stilbene derivatives as human 5-HT6 receptor antagonists from the root of Caragana sinica. / Kim, Dong Hyuk; Kim, Soon Hee; Kim, Hyoung Ja; Jin, Changbae; Chung, Kwang Chul; Rhim, Hyewhon.

In: Biological and Pharmaceutical Bulletin, Vol. 33, No. 12, 01.12.2010, p. 2024-2028.

Research output: Contribution to journalArticle

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T1 - Stilbene derivatives as human 5-HT6 receptor antagonists from the root of Caragana sinica

AU - Kim, Dong Hyuk

AU - Kim, Soon Hee

AU - Kim, Hyoung Ja

AU - Jin, Changbae

AU - Chung, Kwang Chul

AU - Rhim, Hyewhon

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