In vitro anti-mutagenic effect of magnolol against direct and indirect mutagens.
Magnolol, a component of the bark of Magnolia obovata, has been reported to possess various biological activities, such as anti-carcinogenicity, anti-promotion activity and anti-oxidative activity. These findings suggest potential for this compound in cancer chemoprevention. Interestingly, there have been no reports to date on the potential anti-mutagenic activity of magnolol, involving inhibition of initiation processes of the primary stage of carcinogenicity. In this study, anti-mutagenic activity of magnolol against mutagenicity induced by direct mutagens [1-nitropyrene (1-NP), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)] and indirect mutagens [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), benzo(a)pyrene (B(a)P), 2-aminoanthracene (2-AA) and 7,12-dimethylbenz[a]anthracene (DMBA)] were investigated using the bacterial mutagenicity test (Ames test). Results show that magnolol strongly inhibits mutagenicity induced by indirect mutagens, but does not affect direct mutagens. To elucidate the mechanism of this effect against indirect mutagens, effect of magnolol on CYP1A1- and CYP1A2-related enzyme activities of ethoxyresorufin-O-deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) were investigated. Magnolol strongly and competitively suppressed these enzyme activities, suggesting it inhibited mutation induced by indirect mutagens through suppression of CYP1A1 and CYP1A2 activity.
Saito
Junichiro
J
Drug Safety Research Laboratories, Astellas Pharma Inc. 1-8, Azusawa 1-chome, Tokyo 174-8511, Japan. junichiroh.saitoh@jp.astellas.com
Sakai
Yoshimichi
Y
Nagase
Hisamitsu
H
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity; D007700:Kinetics; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives / Q000633:toxicity; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011810:Quinoxalines / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
C432523:2-amino-3-methylimidazo(4,5-f)quinoxaline; D000873:Anthracenes; D016587:Antimutagenic Agents; D001713:Biphenyl Compounds; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D017705:Lignans; D009153:Mutagens; D011810:Quinoxalines; C005498:magnolol; D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; C013525:ENNG; D015127:9,10-Dimethyl-1,2-benzanthracene; C006593:2-anthramine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C023847:Glu-P-2