Effect of multiple doses of N-methyl-N-nitrosourea, an end product of methylguanidine (found in processed food), on the fertility of female Swiss albino mice.

Methylguanidine, an originator of carcinogenic methylnitrosourea, has been found in many animal meats and processed stored food often in high concentration. The present study was designed to understand the multiple dose effect of N-methyl-N-nitrosourea (MNU), an end product of methylguanidine, in Swiss albino mice fertility as well as cancer induction. Accordingly, a total of five experimental groups of animal (female Swiss albino mice) were taken, considering group-I as vehicle control and group-II-V as treatment groups (whereas group-II-Vwere treated with single to quadruple doses of 50 mg/kg of MNU respectively in a three weeks interval). After accomplishment of MNU injection, each female mice was mated with male mice to check the fertility efficiency. The results of the study indicated that, mice treated with highest number of MNU doses were 42.85% less efficient in getting pregnant than the control mice. There were noted changes in body weight, food and water intake upon MNU-exposure compared to control group. A significant increase in cumulative weight of vital female organs like uterus and ovary were also observed in mice injected with quadruple doses of MNU (50 mg/kg) compared to control mice. The findings of the study suggest the direct effect of MNU in pregnancy, without any cancer incidence in the vital female organs of Swiss albino mice.

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability.

Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.

Mahanine, A dietary phytochemical, represses mammary tumor burden in rat and inhibits subtype regardless breast cancer progression through suppressing self-renewal of breast cancer stem cells.

Mahanine (MH), a carbazole alkaloid isolated from an edible plant (Murraya koenigii), potentially inhibits the growth of altered subtypes of breast cancer cells in vitro and significantly reduced the mammary tumor burden in N-Methyl-N-nitrosourea (MNU) induced rat. The experimental results showed that 20-25 µM of MH for 24 h of treatment was very potent to reduce the cell proliferation through apoptosis with arresting the cells in G0/G1 in both ER+/p53WT MCF-7 and triple negative/p53Mut MDA-MB-231 cells. On the other hand, 10-15 µM of MH exposure to those two cell lines, caused inhibition of mammosphere formation and reduction of CD44high/CD24low/epithelial-specific antigen-positive (ESA+) population, which ultimately led to loss of self-renewal ability of breast cancer stem cells. Further, in vivo observation indicated that intraperitoneal injection of MH for four weeks with a dose of 50 mg/kg body weight thrice in a week, significantly (P =  0.03) reduced the mammary tumor weight in MNU induced rat. In conclusion, this study provides the novel insight into the mechanism of MH mediated growth arrest in subtype irrespective breast cancer progression.