Antimutagenic activity of polymethoxyflavonoids from Citrus aurantium.
The methanol extract from Citrus aurantium showed a suppressive effect on umu gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract from C. aurantium was successively re-extracted with hexane, dichloromethane, butanol, and water. A dichloromethane fraction showed a suppressive effect. The suppressive compounds in the dichloromethane fraction were isolated by SiO(2) column chromatography and identified as tetra-O-methylscutellarein (1), sinensetin (2), and nobiletin (3) by EI-MS and (1)H- and (13)C NMR spectroscopy. These compounds suppressed the furylfuramide-induced SOS response in the umu test. Gene expression was suppressed 67%, 45%, and 25% at a concentration of 0.6 micromol/mL, respectively. The ID(50) value (50% inhibition dose) of compound 1 was 0. 19 micromol/mL. These compounds were assayed with other mutagens, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes, activated Trp-P-1, and UV irradiation. These compounds showed of all mutagen-induced SOS response in the umu test. In addition, compounds 1-3 exhibited antimutagenic activity in the S. typhimurium TA100 Ames test.
Miyazawa
M
M
Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka-shi, Osaka 577-8502, Japan. miyazawa@apch.kindai.ac.jp
Okuno
Y
Y
Fukuyama
M
M
Nakamura
S
S
Kosaka
H
H
D016587:Antimutagenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D002957:Citrus; D005419:Flavonoids / Q000494:pharmacology*; D005668:Furylfuramide; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry*; D012486:Salmonella typhimurium
D016587:Antimutagenic Agents; D002273:Carcinogens; D005419:Flavonoids; D010936:Plant Extracts; D005668:Furylfuramide