Potential antigenotoxicity assessment of Ziziphus jujuba fruit

Abstract

Ziziphus jujuba Mill. fruits are nutritionally rich and have a broad spectrum of health benefits. In this work we hypothesized that this natural product rich in polyphenols might protect humans against DNA damage and its consequences. This has led to our investigation to find out if the fruit extract showed an ability to decrease the frequency of DNA damage (antigenotoxicity) induced by two known genotoxins namely an alkylating agent methyl methane sulphonate (MMS) and a reactive oxygen species (ROS) inducer hydrogen peroxide (H2O2).Human lymphocytes were incubated with the Ziziphus fruit ethanol extracts (ZFE) or betulinic acid (BA) followed by an exposure to either 50 μM of MMS or 250 μM of H2O2. Results suggest that ZFE (250, 500, 1000 μg/ml) and BA (10, 20, 40 μg/ml) were able to inhibit the DNA damaging effect caused by MMS and H2O2 indicative of their protection against the genotoxin. This could be attributed to the interactions of the phenolics, flavonoid and BA present in the fruits.Additional in vivo experiments were carried since BA is an important phytochemical detected in ample amounts in the fruit extract. Mice were primed with BA (2.5, 5.0 and 10 mg/kg body weight) for a period of 6 days. The animals were injected with MMS (10 mg/kg body weight) 24 h later and sacrificed. The genotoxic activity of MMS was inhibited in a dose – related manner by BA. BA reduced the frequency of MMS – induced DNA damage in liver, kidney and bone marrow cells of mice thereby exhibiting its antigenotoxic properties. It could also reduce total glutathione level, lipid peroxidation and hydrogen peroxide content in liver cells of mice through the up-regulation of antioxidant enzymes. Therefore taking into account the antioxidant and antigenotoxic properties, the consumption of the Ziziphus fruit should be more popularized worldwide.