Inhibition by an extract of Ocimum sanctum of DNA-binding activity of 7,12-dimethylbenz[a]anthracene in rat hepatocytes in vitro.

Ocimum sanctum is a traditional medicinal plant. Previous studies have shown that extracts of O. sanctum inhibit the induction of skin papillomas in mice by 7,12-dimethylbenz[a]anthracene (DMBA). In the present study, primary cultures of rat hepatocytes were treated with 0-500 microg of O. sanctum extract for 24 h and then with DMBA (10 or 50 microg) for 18 h. Cells were then harvested and their DNA was isolated and analyzed by 32P-postlabelling. A significant reduction in the levels of DMBA-DNA adducts was observed in all cultures pretreated with O. sanctum extract. This effect was more pronounced at the lower dose of DMBA (10 microg). Hepatocytes which were treated with the highest dose of extract (500 microg) showed a maximum reduction of 93% in the mean values of DMBA-DNA adducts. The viability of the cells was not adversely affected by pretreatment with extract. Our findings suggest that O. sanctum leaf extract blocks or suppresses the events associated with chemical carcinogenesis by inhibiting metabolic activation of the carcinogen.

Chemopreventive action of Liv. 52 on DMBA-induced papillomagenesis in skin of mice.

DMBA (195 nmol/50 microliters of acetone/animal) was applied topically over the dorsal skin of the mice and tumors were promoted by repeated applications of croton oil (1% in acetone, three times per week) after two weeks of DMBA application. Skin papillomas appeared in 100% animals in control as well as in groups treated orally with Liv. 52 at post-initiational stages and continuously at peri-initiational and post-initiational stages of papillomagenesis. When Liv. 52 was given orally at the peri-initiational stage of papillomagenesis, the percentage of mice bearing tumors was 75% and the tumor mean per mouse was reduced to 4.0 +/- 1.63 as compared to 7.5 +/- 3.54 in the control group after 15 weeks of observation. The tumor mean per mouse was observed to be 4.75 +/- 0.55 and 2.5 +/- 0.57 in the groups treated orally with Liv. 52 at the post-initiational stages and continuously at peri-initiational and post-initiational stages of papillomagenesis respectively. Similarly, the cumulative number of papillomas after 15 weeks was 30 in the control group, which was reduced to 10 in the animals treated with Liv. 52 continuously at peri-initiational and post-initiational stages. The cumulative number of papillomas was also reduced to 16 and 19 in animals treated with Liv. 52 at peri-initiational and post-initiational stages, respectively.

Modulatory influence of Brassica compestris Linn var sarson on phase-II carcinogen metabolizing enzymes and glutathione levels in mice.

The present study reports the modulatory influence of 95% ethanolic extract from the seeds of B. compestris on the activity of phase-II enzymes such as glutathione S-transferase (GST), DT-diaphorase (DTD) and reduced glutathione (GSH) level in the skin, lung, kidney and forestomach of the mouse. Oral treatment with the seed extract at 800 mg/kg body wt. for 15 days significantly elevated GST in lung and forestomach and DT-diaphorase in forestomach and skin and GSH level in lung, kidney forestomach and skin. The lower dose 400 mg/kg body wt was effective only in inducing GST and DT-diaphorase activity in forestomach and reduced glutathione level in lung. The findings suggest that B. compestris seed extract may block or suppress the events associated with chemical carcinogenesis at least in part, by inducing metabolic detoxification of the carcinogen.

Chemopreventive action by an extract from Ocimum sanctum on mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid soluble sulfydryl level.

We report the chemopreventive property of an ethanolic extract of the leaves of Ocimum sanctum (a traditional medicinal plant) on 7,12-dimethylbenz[a]anthracene induced skin papillomagenesis in male Swiss albino mice. A significant reduction in the values of tumor incidence, average number of tumors per tumor bearing mice and the cumulative number of papillomas was observed in mice treated topically with the leaf extract of O. sanctum at either the peri-initiational, post-initiational stages or continuously at peri- and post-initiational stages of papillomagenesis as compared to the corresponding control group. Topical application of Ocimum leaf extract for 15 days resulted in significant 2-fold elevation of reduced glutathione content in the skin of mice (p < 0.05). Similarly, glutathione S-transferase activity was also observed to be significantly elevated by 25% compared with the control group (p < 0.05) following Ocimum extract treatment.

Modulatory influence of alcoholic extract of Ocimum leaves on carcinogen-metabolizing enzyme activities and reduced glutathione levels in mouse.

The present study reports the modulatory influence of alcoholic extract from the leaves of Ocimum sanctum on the activities of cytochrome p-450, cytochrome b5, and aryl hydrocarbon hydroxylase enzymes in the liver and glutathione-S-transferase and reduced glutathione level in the liver, lung, and stomach of the mouse. Oral treatment with the leaf extract at 400 and 800 mg/kg body wt for 15 days would significantly elevate the activities of cytochrome p-450 (p < 0.05), cytochrome b5 (p < 0.01, p < 0.001), aryl hydrocarbon hydroxylase (p < 0.05), and glutathione S-transferase (p < 0.05, p < 0.01), all of which are important in the detoxification of carcinogens as well as mutagens. Moreover treatment with 400 and 800 mg/kg body wt of Ocimum extract for 15 days also significantly elevated extrahepatic glutathione-S-transferase (p < 0.05, p < 0.01). The reduced glutathione level was also elevated by treatment with the leaf extract in liver, lung, and stomach tissues (p < 0.01, p < 0.001). Mice fed a diet containing 0.75% butylated hydroxyanisole (positive control) revealed no alteration in the basal hepatic cytochrome p-450 and aryl hydrocarbon hydroxylase level, but hepatic cytochrome b5 and glutathione S-transferase activity in hepatic and extrahepatic organs were elevated in a time-responsive manner (p < 0.05, p < 0.001). The observations suggest further exploitation of the Ocimum leaf extract or its active principle(s) for the chemoprevention of chemical carcinogenesis in different animal model systems.