Antioxidative and modifying effects of a tropical plant Azadirachta indica (Neem) on azoxymethane-induced preneoplastic lesions in the rat colon.

The purpose of the present study was to examine whether Neem leaf (Azadirachta indica) has short-term chemopreventive effects on endpoint preneoplastic lesions involved in rat colon carcinogenesis and might also exert antioxidative activity. Forty- two male F344 rats were randomly divided into 6 experimental groups. Groups 1 to 4 were given a subcutaneous injection of azoxymethane (AOM, 20 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of AOM, rats in groups 2 to 4 received an aqueous extract of Neem leaf (20, 100, and 250 mg/kg, respectively) by gavage 3 times per week, for 5 weeks. Rats in group 5 also were given the Neem extract by gavage feeding 3 times per week for 5 weeks, while group 6 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary feeding of the Neem extract at all dose levels significantly inhibited the induction of aberrant crypt foci (ACF) (P<0.0002), when compared to the AOM-treated group (group 1). In groups 2 to 4, treatment of rats with the Neem extract also significantly decreased the proliferating cell nuclear antigen (PCNA) labeling indices (P<0.0006) of colon epithelium and ACF. Moreover, the Neem extract also showed antioxidative activity. The finding that dietary Neem has possible chemopreventive effects in the present short-term colon carcinogenesis bioassay suggests that longer-term exposure may cause suppression of tumor development.

Growth inhibitory activities of crude extracts obtained from herbal plants in the Ryukyu Islands on several human colon carcinoma cell lines.

There is increasing interest in the use of herbs for the treatment of human diseases including cancer. Therefore, the purpose of this study was to determine whether crude extracts obtained from 44 herbal plants in the Ryukyu Islands might contain components capable of inhibiting the growth of a variety of human colon carcinoma cell lines. Leaves, roots and other parts of the plants were extracted with chloroform, and the crude extracts were dissolved in dimethylsulfoxide and used for the experiments. Extracts of Hemerocallis fulva, Ipomoea batatas, Curcuma longa, and Nasturium officinale caused marked dose-dependent growth inhibition, with IC(50) values in the range of 10-80 mug/ml. With the HCT116 cell line, the extracts of Hemerocallis fulva and Ipomoea batatas induced G1 cell cycle arrest after 48 h of treatment. In addition, we found that extracts of Curcuma longa, and Nasturium officinale induced apoptosis in these cells after 48 h of treatment. The present studies are the first systematic examination of the growth inhibitory effects of crude extracts obtained from herbal plants in the Ryukyu Islands. The findings provide evidence that several plants in the Ryukyu Islands contain components that may have anticancer activity.

Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat.

The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin. This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.