Scientific publications
Symphorien Talom Mabou* (Corresponding author)
Claude Danielle Bilanda
Bernes Rivaldo Tadah Kahou
Ferdinand Tameu Meuladje
IBRO Neuroscience Reports
Background Olfactory dysfunction is a debilitating yet under-investigated sequela of ischemic stroke, for which no approved pharmacological intervention currently exists. Despite the documented ethnomedicinal use of Lantana camara L. in Cameroon for post-stroke impairments, its neuroprotective potential against ischemia-induced olfacto-mnemonic axis damage remains unexplored. Purpose To establish a reproducible rat model of post-stroke olfactory dysfunction and evaluate the neuroprotective effects of an aqueous extract of L. camara (AELC) against global cerebral ischemia-reperfusion-induced olfacto-cognitive deficits. Methods A modified transient global cerebral ischemia-reperfusion model was developed in male Wistar rats via bilateral common and internal carotid artery occlusion. Animals were treated with AELC (140, 280, and 560mg/kg), minocycline (100mg/kg), or piracetam (250mg/kg) as reference compounds. Evaluations encompassed neurological recovery, thermoregulatory profiling, olfacto-cognitive behavioral testing, and biochemical and histological analyses of the olfactory bulb, piriform cortex, prefrontal cortex, and hippocampus. Mechanistic insights were sought through LC-MS phytochemical profiling, in silico ADMET analysis, and curvature-based blind molecular docking against the α7 nicotinic acetylcholine receptor (nAChR; PDB: 7KOX). Results Ischemia-reperfusion induced severe thermoregulatory failure, locomotor deficits, and significant olfactory dysfunction (Hedges' g > 2.00), correlating with acetylcholine depletion, oxidative stress (elevated MDA and nitrites; depleted GSH), and neuroinflammation (elevated IL-1β and TNF-α). Histological examination confirmed significant neuronal pyknosis, ghost cell formation, and architectural disorganization across the olfacto-mnemonic axis. AELC at 280 and 560mg/kg effectively reversed these deficits, restoring cholinergic tone (p < 0.001) and preserving neuronal microarchitecture comparably to reference compounds. LC-MS and in silico analyses identified Salvigenin and Kigelinone as promising bioactive leads with favorable drug-likeness and high predicted membrane permeance. Kigelinone exhibited predicted binding interactions at a site topographically consistent with known allosteric modulators of α7 nAChR, forming a hydrogen bond with Ala262 of the M2 transmembrane helix, a mechanistic hypothesis warranting functional validation. Conclusion These findings establish a reliable rat model of post-stroke olfactory dysfunction and demonstrate that L. camara confers significant neuroprotection by modulating the cholinergic-antioxidant-neuroinflammatory axis, validating its ethnomedicinal use and offering a promising natural scaffold for the development of targeted therapeutics against ischemic brain injury.
