Post-treatment with Cnidoscolus aconitifolius leaf extract ameliorates neurological and behavioral deficits following cerebral ischemia-reperfusion in rats by modulating oxidative, inflammatory, apoptotic, and neurotransmitter pathways

Oxidative and inflammatory pathways underlie the neuropathology of ischemic stroke, a neurological disease responsible for death and disability in many people worldwide. Studies showed Cnidoscolus aconitifolius exhibited antioxidant, anti-inflammatory, and memory-enhancing activities in rodents. However, its neuro-protective activities in post-stroke events remain poorly understood. This study sought to investigate the neuroprotective activities of an aqueous leaf extract of Cnidoscolus aconitifolius in rats after ischemia/reperfusion. Forty rats were assigned to five experimental groups as follows: Groups 1 (sham control) and 2 (ischemia/ reperfusion control) received distilled water (10 mL/kg), respectively. Group 3-5 had Cnidoscolus aconitifolius (50,100, and 200 mg/kg, p.o.) for seven days, following induction of ischemic stroke using bilateral common carotid artery occlusion (BCCAO) procedure. We evaluated neurological, motor, and memory skills on day seven following reperfusion. Oxidative stress/antioxidant biomarkers, myeloperoxidase, pro-inflammatory cytokines (TNF-α, IL-6), nuclear factor kappa B (NF-κB), glutamic acid decarboxylase, apoptotic biomarker (caspase-3) contents, neuropathological alterations, and serum lipid profile were determined. The results show that Cnidoscolus aconitifolius post-treatment significantly attenuated neurological, motor, and memory deficits in rats after reperfusion in the BCCAO model. Furthermore, Cnidoscolus aconitifolius post-treatment significantly reduced brain oxidative stress biomarkers, myeloperoxidase, pro-inflammatory cytokines, NF-κB, and caspase-3, while normalizing serum lipid profiles in rats with ischemic stroke. Cnidoscolus aconitifolius administration reduces brain damage, significantly enhances neuronal viability, increases neuronal antioxidant defenses, and increases glutamic acid decarboxylase activity in ischemic rats after reperfusion. The findings demonstrated that post-treatment with Cnidoscolus aconitifolius enhances functional recovery in ischemic rats after reperfusion. This recovery is driven by the activation of neuroprotective pathways, as evidenced by reduced brain damage, increased glutamic acid decarboxylase activity, and enhanced antioxidant defenses.