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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Peroxisome proliferator-activated receptor gamma ligands isolated from adlay seed (Coix lacryma-jobi L. var. ma-yuen

Hiroshi Yokoi¹, Hajime Mizukami, Akito Nagatsu

¹Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, Japan.

Biological & Pharmaceutical Bulletin

|April 2, 2009

Abstract:

Through screening for natural ligands against peroxisome proliferator-activated receptor gamma (PPARgamma) using the PPARgamma luciferase reporter assay, 6 hydroxy unsaturated fatty acids were isolated from adlay seed (Coix lacryma-jobi L. var. ma-yuen STAPF.) extracts with acetone and 70% ethanol. The structures of these compounds were determined via spectral analysis as 13-hydroxy-(9E,11E)-octadecadienoic acid (13-E,E-HODE) (1), 9-hydroxy-(10E,12E)-octadecadienoic acid (9-E,E-HODE) (2), 9-hydroxy-(10E)-octadecenoic acid (3), 10-hydroxy-(8E)-octadecenoic acid (4), 8-hydroxy-(9E)-octadecenoic acid (5), 11-hydroxy-(9Z)-octadecenoic acid (6). 9-E,E-HODE (2) exhibited the most potent PPARgamma agonist activity of the isolated hydroxy unsaturated fatty acids. 9-E,E-HODE (2) and 13-E,E-HODE (1) are the respective geometrical isomers of 9-hydroxy-(10E,12Z)-octadecadienoic acid and 13-hydroxy-(9Z,11E)-octadecadienoic acid, both of which are likely to be natural PPARgamma agonists produced in various mammalian cells, suggesting that 9-E,E-HODE may also act as PPARgamma agonist.

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