title: Inhibition of glycogen synthase kinase-3β by falcarindiol isolated from Japanese Parsley (Oenanthe javanica).
abstract: A new biological activity of falcarindiol isolated from Japanese parsley (Oenanthe javanica) using the mutant yeast YNS17 strain (zds1Δ erg3Δ pdr1Δ pdr3Δ) was discovered as an inhibitor of glycogen synthase kinase-3β (GSK-3β). Falcarindiol inhibited GSK-3β in an ATP noncompetitive manner with a Ki value of 86.9 μM using a human enzyme and luminescent kinase assay platform. Falcarindiol also both suppressed gene expression of glucose-6-phosphatase (G6Pase) in rat hepatoma H4IIE cells and protected mouse neuroblastoma HT22 cells from glutamate-induced oxidative cell death at 10 μM. During an oral glucose tolerance test (OGTT), the blood glucose level was significantly decreased in the rats treated with oral administration of O. javanica extract containing falcarindiol (15 mg/kg). These findings indicate that Japanese parsley could be a useful food ingredient against type-2 diabetes and Alzheimer's disease.
authors.affiliation: Chemical Biology Laboratory, The United Graduate School of Agricultural Sciences, §Graduate School of Agriculture, and ∥Faculty of Agriculture, Iwate University , Morioka, Iwate 020-8550, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Hiroko
authors.initials: H
authors.lastname: Seino
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Nakano
authors.forename: Takumi
authors.initials: T
authors.lastname: Satoh
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ogane
authors.forename: Saori
authors.initials: S
authors.lastname: Suwa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koshino
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D053280:Diynes / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D031050:Oenanthe / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D051381:Rats
chemical_list: D053280:Diynes; D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D010936:Plant Extracts; C034379:falcarindiol; D038362:Glycogen Synthase Kinase 3; D005952:Glucose-6-Phosphatase; D005947:Glucose