Cancer Letters

Cancer Letters

Volume 163, Issue 2, 26 February 2001, Pages 163-170
Cancer Letters

The inhibitory effects of mangiferin, a naturally occurring glucosylxanthone, in bowel carcinogenesis of male F344 rats

https://doi.org/10.1016/S0304-3835(00)00678-9Get rights and content

Abstract

Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-beta-d-glucoside, is one of xanthone derivatives and C-glucosylxanthones, is widely distributed in higher plants and is one of constituents of folk medicines. Recent studies showed that mangiferin has a potential as an anti-oxidant and an anti-viral agent. In this study, we examined the effects of mangiferin in rat colon carcinogenesis induced by chemical carcinogen, azoxymethane (AOM). We performed two experiments: a short-term assay to investigate the effects of mangiferin on the development of preneoplastic lesions by AOM, aberrant crypt foci (ACF), and the following long-term assay for the influence of mangiferin on tumorigenesis induced by AOM. In the short-term assay, 0.1% mangiferin in a diet significantly inhibited the ACF development in rats treated with AOM compared to rats treated with AOM alone (64.6±22.0 vs. 108.3±43.0). In the long-term assay, the group treated with 0.1% mangiferin in initiation phase of the experimental protocol had significantly lower incidence and multiplicity of intestinal neoplasms induced by AOM (47.3 and 41.8% reductions of the group treated with AOM alone for incidence and multiplicity, respectively). In addition, the cell proliferation in colonic mucosa was reduced in rats treated with mangiferin (65–85% reductions of the group treated with AOM alone). These results suggest that mangiferin has potential as a naturally-occurring chemopreventive agent.

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),

References (26)

  • N Yoshimi et al.

    Modifying effects of fungal and herb metabolites on azoxymethane-induced intestinal carcinogenesis in rats

    Jpn. J. Cancer Res.

    (1992)
  • E Quisumbing

    Medicinal Plants of the Philippines

    Katha Publishing Co & JMC Press, Quezon

    (1978)
  • S.K Bhattacharya et al.

    Monoamine oxidase-inhibiting activity of mangiferin isolated from canscora decussata

    Naturwissenschaften

    (1972)
  • Cited by (0)

    View full text