Lantana camara L. (Verbenaceae) attenuates Ischemia-induced olfactory dysfunction by targeting the α7 nAChR allosteric site and mitigating oxidative-inflammatory cascades in the rat olfactory-memory axis.

Authors

Symphorien Talom Mabou, Claude Danielle Bilanda, Bernes Rivaldo Tadah Kahou, Ferdinand Tameu Meuladje, Antoine Kavaye Kandeda

Published in

IBRO neuroscience reports. Volume 21. Pages 238-263. Epub Jul 01, 2026.

Abstract

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.
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.
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 560 mg/kg), minocycline (100 mg/kg), or piracetam (250 mg/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).
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 560 mg/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.
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.

PMID:
42437013
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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