Akinleye_2026_Curr.Res.Physiol_9_100185

Neurotoxicity induced by environmental pollutants such as phenanthrene, a polycyclic aromatic hydrocarbon (PAH), has been linked to oxidative stress, inflammatory responses and cholinergic crisis contributing hugely to neurodegenerative conditions. In this light, this study explored neuroprotective potentials of Aspilia africana (AA) against phenanthrene-induced neurotoxicity in rats. Seven bioactive phytochemicals in AA were evaluated by elucidating their binding dynamics P2X7 and predict their pharmacokinetic properties using molecular docking and ADMET prediction. Neurotoxicity was induced by oral administration of phenanthrene for 26 days, followed by oral treatment with aqueous extract of AA (500 mg/kg or 750 mg/kg) or Chrysin (25 mg/kg) for 18 days. Interleukin-1 beta (IL-1beta), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Inducible Nitric Oxide Synthase (iNOS), Nuclear Factor kappa B (NF-kappaB) Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), Catalase (CAT) Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Acetylcholinesterase AChE levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. Molecular docking and ADMET prediction were done using CB-Dock, mcule and SwissADME servers. Phenanthrene administration significantly elevated pro-inflammatory cytokines and, (p < 0.05), and reduced IL-10. Conversely, antioxidant enzymes activity was markedly reduced, along with decreased AChE activity. AA significantly downregulated the pro-inflammatory cytokines and upregulated anti-inflammatory cytokine (IL-10) and restored antioxidant levels in a dose-dependent manner. AChE activity was also normalized, and Nrf2 expression was significantly upregulated. The seven identified most bioactive compounds of AA including chrysin docked favourably with P2X7 receptor with binding affinities between -9.9 and -5.6 kcal/mol. The ADMET profiles showed drug ability, GI absorptions, and moderate or no toxicity for all. AA confers neuroprotection against phenanthrene-induced toxicity by attenuating inflammation, enhancing antioxidant responses via Nrf2 pathway activation, and modulating cholinergic imbalance.