Mechanistic insights into <i>Moringa oleifera</i> leaf bioactive against cytotoxic stress: an integrative approach

Exposure to ionizing radiation during medical diagnostics and cancer therapy often results in collateral damage to healthy cells, primarily due to the generation of free radicals. <i>Moringa oleifera</i> (MO), known for its rich antioxidant profile, may offer protective effects against such damage. This study investigates the radioprotective potential of MO leaf extract against DNA damage induced by bleomycin and X-irradiation. The antioxidant capacity of the extract was evaluated using DPPH radical scavenging assays, which revealed a dose-dependent increase in free radical inhibition, from 21.51% at 0.2 mg/mL to 51.07% at 1 mg/mL. UV-Vis spectral analysis showed strong absorbance around 370 nm, indicating the presence of flavonoid compounds. HPLC profiling further confirmed the phytochemical composition, with prominent peaks corresponding to kaempferol and related flavonoids, indicating their substantial abundance in the extract. <i>In vitro</i> experiments using human peripheral blood lymphocytes treated with MO demonstrated a significant (<i>p</i> < 0.0001) reduction in chromosomal aberrations and DNA strand breaks following exposure to bleomycin (40 µg/mL) and X-irradiation (2 Gy). Furthermore, molecular docking and 200 ns molecular dynamics simulations revealed that kaempferol, a major MO constituent, exhibited strong binding affinity with the Keap1-Nrf2 complex, suggesting activation of antioxidant gene expression. Overall, the findings support MO's role as a natural, low-toxicity radioprotective agent and highlight the complementary value of computational approaches alongside cytogenetic assays in validating therapeutic potential.