Chronic excess ethanol exacerbates post-ischaemic vascular dementia in rats: the potential of Ficus platyphylla Delile to reverse motor and behavioral sequelae

• 30-days treatment with 35% ethanol (5 mL/kg, EtOH) significantly exacerbates ischaemic stroke-induced damage. • Ficus platyphylla effectively reversed memory impairment sequelae induced by EtOH + CIS across all administered doses. • Ficus platyphylla also reversed motor impairment sequelae induced by EtOH + CIS at all tested doses. • Ficus platyphylla demonstrated anticholinesterase activity at doses of 200 and 300 mg/kg, antioxidant effects at doses of 100, 200, and 300 mg/kg, and anti-inflammatory properties at all administered doses. • At therapeutic doses (200mg/kg), the aqueous extract of Ficus platyphylla is safe and non-toxic. Ficus platyphylla Delile (Moraceae) is traditionally used in Africa to treat cognitive disorders, epilepsy, and psychosis. To evaluate the effect of Ficus platyphylla (FP) trunk bark aqueous extract on ischaemic stroke-induced vascular dementia, exacerbated by chronic and excessive ethanol exposure in adult rats. Fifty-eight male rats were divided into nine groups: Normal group received distilled water (DW) at 10 mL/kg (n=4), SHAM group received ethanol (EtOH) 35% at 5 mL/kg (n=10), Negative group 1 underwent the CIS procedure (n=4), Negative group 2 underwent the CIS procedure and received EtOH (n=10), positive group 1 received Aspirin at 30 mg/kg (n=6), Positive group 2 received Piracetam at 200 mg/kg (n=6) and Experimental groups (3 groups) treated with FP aqueous extract at doses of 100, 200, and 300 mg/kg (n=6 each). Rats were pretreated with ethanol for 30 days, followed by the CIS procedure. Four rats from the first four groups were randomly selected and sacrificed to validate the model. The remaining rats underwent 14 days of treatment with FP extract or reference substances. Memory impairment was evaluated using the Y-maze test (YMT) and novel object recognition test (NORT). Motor activity was assessed through the grid suspension test (GST) and Raised Beam Test (RBT). Oxidative and nitrosative stress markers, pro-inflammatory cytokine levels, and acetylcholinesterase (AchE) activity were measured in brain homogenates after euthanasia. Histological analysis of the hippocampus and cortex was conducted. Acute and sub-acute toxicological studies of FP extract were carried out in accordance with OECD guidelines (425 for acute toxicity and 407 for sub-acute toxicity). Model validation showed that combined EtOH and CIS increased neurological scores (p < 0.01), IL-1β levels (p < 0.05), NO levels (p < 0.01), and MDA levels (p < 0.001), while reducing SOD (p < 0.001) and GPx activity (p < 0.05) compared to rats subjected only to the CIS procedure. Treatment with FP aqueous extract (100, 200, and 300 mg/kg) improved (p < 0.001) spontaneous alternation in the YMT and discrimination index in the NORT, compared to the EtOH + CIS group. At 200 and 300 mg/kg, FP extract significantly (p < 0.001) increased grip time in the GST and reduced latency time (p < 0.01) in the RBT, reduced (p < 0.01) AchE activity, MDA concentration, and NO levels, while enhancing SOD and GPx activity, compared to the EtOH + CIS group. The extract also decreased (p < 0.001) IL-1β, TNF-α, and IL-6 levels across all doses, compared to the EtOH + CIS group. No signs of toxicity were observed at therapeutic doses of FP extract. The aqueous extract of Ficus platyphylla trunk bark (100, 200, and 300 mg/kg) reversed memory impairment and motor deficits induced by cerebral ischaemic surgery and exacerbated by chronic excessive ethanol consumption, with the 200mg dose as the most active dose. These neuroprotective effects may be attributed to the extract’s anticholinesterase, antioxidant, and anti-inflammatory properties.