The inhibitory effects of mangiferin, a naturally occurring glucosylxanthone, in bowel carcinogenesis of male F344 rats
Introduction
Cancer chemoprevention is a very promising means to control cancer [1], [2]. The minor dietary constituents are very important as chemopreventive agents [2]. In our search for effective cancer chemopreventive agents, we have focused on an Asian-transitional medicine using herbs with an anti-oxidant activity. We have previously reported the inhibitory effects of some oriental herbs in rat colon carcinogenesis [3]. In this study, we now demonstrate the inhibition of colon tumorigenesis in rats by mangiferin, which is extracted from the bark of Mangifera indica.
Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-beta-d-glucoside, is one of xanthone derivatives and C-glucosylxanthones [4]. This chemical is widely distributed in higher plants such as Anacardiaceae and Gentianaceae families, especially in the leaves and the bark. In the Philippines, the mangos leaves are prepared as a tea, and the juice of the leaf is considered to be useful in bleeding dysentery [5]. The bark and seeds are astringent. In the traditional Indian system of medicine, mangiferin is also used for melancholia and nervous debility [6]. Furthermore, one of traditional Chinese medicines, sann-Joong-kuey-jian-tang, also includes the mangiferin [7]. Recently, Sato et al. [8] reported that mangiferin had a strong antioxidative potency as scavengers of free radicals.
Aberrant crypt foci (ACF) were identified as preneoplastic markers in rat colon carcinogenesis [9]. This has allowed ACF to be used as short-term markers in chemoprevention studies [10]. Therefore, to determine whether mangiferin might work as a chemopreventive agent, we first performed a short-term assay, which examines ACF induced by azoxymethane (AOM) in rat colonic mucosa. Next we conducted a long-term experiment to investigate the inhibitory effects of mangiferin in AOM-induced colon carcinogenesis in rats.
Section snippets
Chemicals
Mangiferin was extracted from Mangifera indica Linn in our laboratory. In brief, the bark of mango was extracted in hot water for 3 h. After the filtered solution was cooled down and dried up, it was dissolved in methanol. Mangiferin in the solution was purified by silica gel column chromatography. The extracted mangiferin was identified by comparison to an authentic standard by nuclear magnetic resonance. The purity was more than 99.5%. The molecular structure of mangiferin is shown in Fig. 1.
Results
Table 1 summarizes body weight, liver weight, and the relative ratio of liver weight to body weight in both experiments at the termination of the experiments. There were no differences of those among groups in Experiment I (Table 1). In Experiment II, although the body and liver weights in groups 8–10 treated with mangiferin for a long duration were lower than those in other groups, the relative ratios were not significantly different among groups (Table 1). Food consumption in all groups was
Discussion
Xanthone derivatives, including mangiferin, are present in common used folk medical preparations in the world. However, little is known about the scientific and medical mechanisms and even toxicological properties. Mangiferin is one of xanthone derivatives and consists of glucose as C-glucosylxanthone. Some xanthone derivatives are mutagenic in Salmonella typhimurium TA100 and TA98 [15], [16], but mangiferin is non-mutagenic [17]. Mangiferin is also used in traditional alternative medicine but
Acknowledgements
We thank K. Takahashi, K. Sato, C. Usui, and T. Kajita in our laboratory for technical support, and Dr H. Kleiner, MD Anderson Cancer Center, for a good advice and editing a manuscript. This work was supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture, Japan, a Grant-in-Aid from the Ministry of Health and Welfare, Japan, and the Program for Promotion of Fundamental Studies in Health Science from the Organization for Pharmaceutical Safety and Research (OPSR),
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