Anticlastogenic and anticarcinogenic potential of Thai bitter gourd fruits.

Thai bitter gourd fruits (Momordica charantia Linn., TBG) has been previously demonstrated to possess phase II detoxificating enzymes inducing properties, as well as the ability to reduce phase I carcinogen activating enzyme activity in rat liver. In addition, it was partially inhibited 7,12-dimethylbenz(a)anthracene (DMBA)- induced mammary gland carcinogenesis in female Sprague-Dawley rats. In this study, we therefore examined the anticlastogenic and anticarcinogenic effect of TBG against clastogens, cyclophosphamide (CYP) and DMBA, in mice using the in vivo erythrocyte micronucleus assay and azoxymethane (AOM)-induced colon carcinogenesis in rats, respectively. For anticlastogenicity test, male mice were fed with modified AIN-76 diets containing 6.25% and 12.5% of ground freeze-dried TBG for 2 weeks prior to administration of clastogens till the end of experiment. Blood samples were collected and counted for reticulocytes by using the fluorescent microscope. For anticarcinogeicity test, male Wistar rats were fed with modified AIN-76 diets containing 5% and 10% ground freeze-dried TBG for 2 weeks prior to, during and 1 week after the completion of AOM administration (15 mg/kg once a week for 2 weeks). It was found that TBG at 6.25% resulted in a significant reduction in micronucleated peripheral reticulocytes (MNRETs) induced by only CYP. Study on anticarcinogenic potential demonstrated that rats fed with TBG diets at the concentration tested developed significantly higher incidence as well as the multiplicities of colon tumors than the control group. These results demonstrated that Thai bitter gourd fruits possesses anticlastogenic potential against clastogen in the mouse. Interestingly, it had no preventive potential against AOM-induced colon carcinogenesis in rat, rather increasing the incidence of colonic neoplasm when giving during the initiation stage.

Quinone reductase inducers in Azadirachta indica A. Juss flowers, and their mechanisms of action.

We have previously shown that the flowers of neem tree (Azadirachta indica A. Juss, family Meliaceae), Thai variety, strongly induced the activity of glutathione S-transferase (GST) while resulting in a significant reduction in the activities of some cytochrome P(450)-dependent monooxygenases in rat liver, and possess cancer chemopreventive potential against chemically-induced mammary gland and liver carcinogenesis in rats. In the present study, 2 chemicals possessing strong QR inducing activity were fractionated from neem flowers using a bioassay based on the induction of QR activity in mouse hepatoma Hepa 1c1c7 cultured cells. Spectroscopic characteristics revealed that these compounds were nimbolide and chlorophylls, having CD (concentration required to double QR specific activity) values of 0.16 and 3.8 mug/ml, respectively. Nimbolide is a known constituent of neem leaves, but was found for the first time here in the flowers. Both nimbolide and chlorophylls strongly enhanced the level of QR mRNA in Hepa 1c1c7 cells, as monitored by northern blot hybridization, indicating that the mechanism by which these constituents of neem flowers induced QR activity is the induction of QR gene expression. These findings may have implication on cancer chemopreventive potential of neem flowers in experimental rats previously reported.