Effects of Roselle (Hibiscus sabdariffa Linn.), a Thai Medicinal Plant, on the Mutagenicity of Various Known Mutagens in Salmonella typhimurium and on Formation of Aberrant Crypt Foci Induced by the Colon Carcinogens Azoxymethane and 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine in F344 rats

Abstract

The 80% ethanol extract of roselle ( Hibiscus sabdariffa Linn.), a medicinal plant in Thailand, was examined for antimutagenic and chemopreventive activity in a colon carcinogenesis model. It reduced about 60–90% of the mutagenicity induced by 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) and other heterocyclic amines 2-amino-3-methylimidazo[4,5- f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5- f]quinoline(MeIQ),2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline(MeIQx),3-amino-1,4-dimethyl-5 H-pyrido[4,3- b]indole (Trp-P-1), 3-amino-1-methyl-5 H-pyrido[4,3- b]indole (Trp-P-2),2-amino-6-methyldipyrido[1,2- a:3′,2′- d]imidazole (Glu-P-1),2-aminodipyrido[1,2- a:3′,2′- d]imidazole (Glu-P-2), at a concentration of 12.5 mg/plate in the Salmonella mutation assay. The extract showed no mutagenicity and no antibacterial activity below this dose. Mutagenicity of methylazoxymethanol (MAM) acetate, which, like PhIP, is a colon carcinogen,was also efficiently inhibited by the roselle extract. To investigate chemoprevention by roselle in a colon carcinogenesis model, we examined the inhibitory effects of the roselle extract in F344 rats in which aberrant crypt focus (ACF) formation was induced by azoxymethane (AOM) and PhIP. In the initiation stage, the number of AOM-induced ACF in the colon was significantly decreased by roselle (17–25%) compared with that in rats treated with AOM alone. The amount of O 6-methylguanine in the colonic mucosa tended to be decreased in the roselle-treated rats. The number of PhIP-induced ACF was also significantly decreased by roselle treatment (22%) at a concentration of 1.0 g/kg body weight in the initiation stage. However, in the post-initiation stage of AOM-induced ACF formation, roselle increased the number of ACF, especially the number of foci which had more than three crypts/focus. These results indicate that roselle has antimutagenic activity against MAM acetate and heterocyclic amines and that it decreases the number of AOM- and PhIP-induced ACF in the initiation stage, although it rather increased the number of ACF in the post-initiation stage.