Essawy_2026_Metab.Brain.Dis_41_

Although a variety of antiepileptic medications are available, their administration often leads to undesirable side effects. In the present study, we investigated the effect of Moringa oleifera leaf extract (MOLE) against neurodegenerative pathophysiology relevant to PTZ-induced epilepsy-like neurobehavior in the hippocampus of rats. Forty male rats were allocated into four groups: control group, MOLE group, PTZ group, and PTZ plus MOLE group. MOLE (300 mg/kg) was administered orally for 35 days, while PTZ (40 mg/kg) was injected intraperitoneally in nine doses on alternate days, commencing on the 18th day. Phytochemical analysis using GC-MS and molecular docking was performed. Animals were behaviorally assessed using open field and elevated plus maze tests. The hippocampal tissue was evaluated for malondialdehyde, nitric oxide, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, tumor necrosis factor-alpha, interleukin-1beta and 6, acetylcholine, acetylcholinesterase, gamma-aminobutyric acid, glutamate, and monoamine oxidase. NF-kB expression, histopathological alterations, caspase-3, and GFAP immunoreactivity were investigated. The GC-MS analysis revealed the presence of various phytochemicals. MOLE attenuated PTZ-induced behavioral changes and improved the oxidant/antioxidant status of the hippocampus. MOLE also reduced the pro-inflammatory cytokines, modulated the neurochemicals, and regulated the expression of NF-kappaB. Furthermore, MOLE improved the histopathological and the immunohistochemical deteriorations in the hippocampus. Molecular docking analysis showed robust binding affinities for the major phytochemicals to proteins involved in neuroinflammation, oxidative stress, and regulation of neurotransmission. These findings highlight the efficacy of MOLE as a potential multi-target approach against PTZ-induced epilepsy-like neurobehavior, attributed to its diverse bioactive phytochemicals with antioxidative, anti-inflammatory, neuromodulator, and NF-kappaB regulatory properties.