Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems

Abstract

Numerous laboratory studies reveal that various naturally occurring dietary substances can modify the patho-physiological process of various metabolic disorders and can be an effective preventive strategy for various diseases, including cancer. Indian Neem tree, Azadirachta indica A. Juss. (family: Meliaceae), contains at least 35 biologically active principles and is widely grown all over the tropics. The effect of two different doses (250 and 500 mg per kilogram body weight) of 80% ethanolic extract of the leaves of Azadirachta indica were examined on drug metabolizing Phase-I and Phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase, and lipid peroxidation in the liver of 7-week-old Swiss albino mice. Also anticarcinogenic potential of Azadirachta indica leaf extract was studied adopting protocol of benzo(a)pyrene-induced fore-stomach and 7,12-dimethyl benz(a)anthracene (DMBA)-induced skin papillomagenesis. Our primary findings reveal its potential to induce only the Phase-II enzyme activity associated mainly with carcinogen detoxification in liver of mice. The hepatic glutathione S-transferase ( P<0.005) and DT-diaphorase specific activities ( P<0.01) were elevated above basal level. With reference to antioxidant enzymes the investigated doses were effective in increasing the hepatic glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) activities significantly (from P<0.005 to P<0.001). Reduced glutathione measured as non-protein sulphydryl was found to be significantly elevated in liver ( P<0.005) and in extrahepatic organs (from P<0.005 to P<0.001) examined in our study. Glutathione S-transferase (GST) and DT-diaphorase (DTD) showed a dose-dependent increase in extrahepatic organs. Chemopreventive response was measured by the average number of papillomas per mouse, as well as percentage of tumor-bearing animals. There was a significant inhibition of tumor burden, in both the tumor model system studied (from P<0.005 to P<0.001). Tumor incidence was also reduced by both the doses of Azadirachta indica extract.