Identification of Coumarins from the Fruit of Citrus hystrix DC as Inhibitors of Nitric Oxide Generation in Mouse Macrophage RAW 264.7 Cells
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- 作者：Akira Murakami ; Guanxin Gao ; Oe Kyung Kim ; Mitsuo Omura ; Masamichi Yano ; Chihiro Ito ; Hiroshi Furukawa ; Suratwadee Jiwajinda ; Koichi Koshimizu ; and Hajime Ohigashi
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：1999
- 出版时间：January 1999
- 年：1999
- 卷：47
- 期：1
- 页码：333 - 339
- 全文大小：197K
- 年卷期：v.47,no.1(January 1999)
- ISSN：1520-5118
文摘
Three known coumarins have been isolated from Citrus hystrix DC as inhibitors of both lipopolysaccharide (LPS) and interferon-
(IFN-)-induced nitric oxide (NO) generation in RAW 264.7 cells.The inhibitory activity of bergamottin (IC50 = 14 
M) was comparable to that of N-(iminoethyl)-L-ornithine (L-NIO) (IC50 = 7.9 M), 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 coumarinsinto groups A-C: (A) bearing an isoprenyl (IP) or a geranyl (GR) group, highly active; (B) bearingan IP group cyclized to a coumarin ring, moderately active; (C) bearing an IP group modified withhydroxyl 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 poorpermeability to the cell membrane.Keywords: Citrus hystrix DC; psoralen; coumarin; nitric oxide; RAW 264.7 cells; structure-activityrelationships
(IFN-)-induced nitric oxide (NO) generation in RAW 264.7 cells.The inhibitory activity of bergamottin (IC50 = 14 M) was comparable to that of N-(iminoethyl)-L-ornithine (L-NIO) (IC50 = 7.9 M), 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 coumarinsinto groups A-C: (A) bearing an isoprenyl (IP) or a geranyl (GR) group, highly active; (B) bearingan IP group cyclized to a coumarin ring, moderately active; (C) bearing an IP group modified withhydroxyl 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 poorpermeability to the cell membrane.Keywords: Citrus hystrix DC; psoralen; coumarin; nitric oxide; RAW 264.7 cells; structure-activityrelationships