Evaluation of the Cytotoxic Effect and Antioxidant Potential of Carpolobia lutea Leaf Extract in a Reserpine-Induced Mouse Model of Depression

Abstract

Carpolobia lutea is traditionally used for various CNS disorders, but its multitarget potential in depression-associated genomic and oxidative damage remains poorly understood. This study investigated the antioxidant and cytotoxic effects of Carpolobia lutea (100, 200, and 400 mg/kg) in a reserpine-induced mouse model of depression. Animals (49 mice) were divided into two groups: a basal control group and a reserpine-treated group (0.2 mg/kg for 15 days). On day 16, they were split into seven groups to evaluate the effect of the ethanolic extract of Carpolobia lutea (CL-E) on oxidative stress. In a separate study, the cytotoxic safety of the extract was evaluated using the Allium cepa assay. This study demonstrated that the reserpine-induced group exhibited a marked elevation in intracellular concentrations of superoxide anion (O₂·⁻) and nitric oxide (NO) (P < 0.05) compared to the control group. However, treatment with CL-E (100, 200, and 400 mg/kg) significantly lowered these levels, bringing O₂·⁻ and NO concentrations to near-baseline levels. In contrast, the levels of intracellular peroxynitrite/hydroxyl radicals (ONOO⁻/·OH) did not change between the experimental groups (P > 0.05) when compared to the basal control. This study also showed elevated lipid peroxidation, followed by decreased brain glutathione content (P < 0.05) in reserpine-induced group when compared with the control. This process was attenuated after treatment with CL-E at 100 – 400 mg/kg, comparable to moclobemide and reserpine-induced groups (P < 0.05). The cytological analysis further confirmed that CL-E at low concentrations below 0.6 mg/ml did not affect the mitotic index of Allium cepa roots, but at higher concentrations has the potential to induce cell proliferation by increasing the mitotic index significantly, though with no chromosomal aberrations in the various stages of cell division. In conclusion, CL-E demonstrates significant antioxidant properties by mitigating reserpine-induced oxidative stress, while the reduction in mitotic index suggests potential cytotoxic activity at higher concentrations.