Neuroprotective effects of Moringa oleifera leaf extract via potential NF-κB modulation in cuprizone-induced demyelination in rats: Integrated in vivo and in silico evidence

Myelin sheath impairment is linked to several neurological disorders; however, effectively counteracting its pathological consequences remains a formidable challenge. Herein, we investigate the neuroprotective potential of Moringa oleifera leaf extract (MOLE) against cuprizone (CPZ)-instigated demyelination in the corpus callosum (CC) of rats. Phytochemical profiling of MOLE was analyzed using gas chromatography-mass spectrometry (GC-MS). For in vivo investigations, adult male Wistar albino rats were assigned into four groups: Group I (control) received corn oil 0.5 mL and distilled water (1 mL) daily by oral gavage for three weeks; Group II (MOLE) received MOLE (300 mg/kg/day) in 1 mL distilled water orally for three weeks; Group III (CPZ) received CPZ (600 mg/kg/day) in 0.5 mL corn oil for one week, followed by 200 mg/kg/day for the next two weeks; Group IV (CPZ + MOLE) received both CPZ and MOLE according to the regimens described for Groups II and III. Neurobehavioral assessments using the rotarod and inverted screen tests revealed notable aberrations in CPZ-treated rats compared to control rats, whereas MOLE administration markedly ameliorated these deficits. Biochemically, CPZ treatment markedly deregulated oxidative stress markers in the CC, increasing malondialdehyde (MDA) and nitric oxide (NO), while reducing reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Consistently, it elevated inflammatory biomarkers, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB), accompanied by histological and ultrastructural anomalies compared with controls and those treated only with MOLE, suggesting its safety profile. Interestingly, co-administration of MOLE normalized oxidative stress and inflammatory markers, potentially through NF-κB orchestration, and correlated with histopathological and ultrastructural improvements. Molecular docking investigations further showed robust binding of bioactive compounds in MOLE within TNF-α and NF-κB active sites, substantiating in vivo findings. Collectively, our findings accentuate the potential prophylactic potency of MOLE against CPZ-induced demyelination.