title: Identification of coumarins from the fruit of Citrus hystrix DC as inhibitors of nitric oxide generation in mouse macrophage RAW 264.7 cells.
abstract: Three known coumarins have been isolated from Citrus hystrix DC as inhibitors of both lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) generation in RAW 264.7 cells. The inhibitory activity of bergamottin (IC(50) = 14 microM) was comparable to that of N-(iminoethyl)-L-ornithine (L-NIO) (IC(50) = 7. 9 microM), whereas oxypeucedanin and 5-[(6',7'-dihydroxy-3', 7'-dimethyl-2-octenyl)oxy]psoralen, structurally different from bergamottin only in their side-chain moieties, were notably less active. Using 21 coumarins, we structurally classified various types of coumarins into groups A-C: (A) bearing an isoprenyl (IP) or a geranyl (GR) group, highly active; (B) bearing an IP group cyclized to a coumarin ring, moderately active; (C) bearing an IP group modified with hydroxyl group(s) and/or having other functional groups except for the IP, completely inactive. Cellular uptake studies suggested that coumarins in group C are inactive because of poor permeability to the cell membrane.
authors.affiliation: Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita, Wakayama 649-6493, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Murakami
authors.forename: G
authors.initials: G
authors.lastname: Gao
authors.forename: O K
authors.initials: OK
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Omura
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: C
authors.initials: C
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
authors.forename: S
authors.initials: S
authors.lastname: Jiwajinda
authors.forename: K
authors.initials: K
authors.lastname: Koshimizu
authors.forename: H
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D009569:Nitric Oxide