title: Identification of CB1/CB2 ligands from Zanthoxylum bungeanum.
abstract: In order to study cannabinoid receptor ligands, a novel plate-based assay was developed previously to measure internalization of CB1/CB2 receptors by determining the change in the intracellular levels of the radiolabeled agonists. This plate-based assay was also used for screening against complex matrices, specifically, in the present study screening for CB1/CB2 receptor activity of extracts for several species of the plant genus Zanthoxylum. The objective of this screen was to identify novel antagonists of the CB1 receptor, which simultaneously displayed agonist activity against the CB2 receptor, since compounds matching this criterion could be potential candidates for the treatment of type-1 diabetes. As a result, two Z. bungeanum extracts were deemed active, leading to the identification of eight compounds, of which compound 7 [(2E,4E,8E,10E,12E)-N-isobutyl-2,4,8,10,12-tetradecapentaenamide, γ-sanshool] was obtained as a promising lead compound.
authors.affiliation: Biomedical Research Center, National Institute on Aging, National Institutes of Health , 251 Bayview Boulevard, Suite 100, Baltimore, Maryland 21224, United States.
authors.forename: Katina S S
authors.initials: KS
authors.lastname: Dossou
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Devkota
authors.forename: Cynthia
authors.initials: C
authors.lastname: Morton
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Guanghua
authors.initials: G
authors.lastname: Lu
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.forename: Ruin
authors.initials: R
authors.lastname: Moaddel
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D008024:Ligands; D015394:Molecular Structure; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D000577:Amides; D063387:Cannabinoid Receptor Antagonists; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C100574:sanshool