title: In vitro evaluation of potential bitterness-masking terpenoids from the Canada goldenrod (Solidago canadensis).
abstract: In a screening of extracts of selected plants native to Ohio against the human bitterness receptor hTAS2R31, a chloroform-soluble extract of the aerial parts of Solidago canadensis (Canada goldenrod) was determined to have hTAS2R31 antagonistic activity and, thus, was fractionated for isolation of potential bitterness-masking agents. One new labdane diterpenoid, solidagol (1), and six known terpenoids, including two labdane diterpenoids (2 and 3), three clerodane diterpenoids (6β-angeloyloxykolavenic acid, 6β-tigloyloxykolavenic acid, and crotonic acid), and a triterpenoid (longispinogenin), were isolated. Among these compounds, 3β-acetoxycopalic acid (2) was found to be the first member of the labdane diterpene class shown to have inhibitory activity against hTAS2R31 activation (IC50 8 μM). A homology model of hTAS2R31 was constructed, and the molecular docking of 2 to this model indicated that this diterpenoid binds well to the active site of hTAS2R31, whereas this was not the case for the closely structurally related compound 3 (sempervirenic acid). The content of 2 in the chloroform-soluble portion of the methanolic extract of S. canadensis was up to 2.24 g/100 g dry weight, as determined by HPLC.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 W. 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Fletcher
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.forename: Ye
authors.initials: Y
authors.lastname: Deng
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vincent
authors.forename: Jay P
authors.initials: JP
authors.lastname: Slack
authors.forename: T Scott
authors.initials: TS
authors.lastname: McCluskey
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Jia
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009820:Ohio; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects*; D036624:Solidago / Q000737:chemistry*; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000098706:Taste Receptors, Type 2
chemical_list: D004224:Diterpenes; D043562:Receptors, G-Protein-Coupled; D013729:Terpenes; C433017:labdane; D000098706:Taste Receptors, Type 2