Effects of Artocarpus heterophyllus Seed Ethanol Extract on Cognitive and Behavioural Deficits in Aluminum Chloride–treated Mice

Exposure to aluminum chloride is known to induce significant neurocognitive impairment, necessitating the exploration of natural bioactive compounds as potential neuroprotective agents. Consequently, this research investigated whether an ethanol extract of Artocarpus heterophyllus seeds could mitigate impairments in cognition, movement, and anxiety-like behaviour in mice exposed to aluminum chloride (AlCl3). Acute oral toxicity was evaluated using the modified Lorke’s method at doses of 1000–4000 mg/kg. Mice were randomly allocated to six groups (n=5): control (distilled water), negative control (AlCl3-induced, untreated), and four pre-treatment groups receiving donepezil (1 mg/kg), or Artocarpus heterophyllus seed ethanol extract (100, 200, or 400 mg/kg) orally an hour prior to intraperitoneal administration of AlCl3 (100 mg/kg). Cognitive and locomotor activities were assessed after 14 days of pretreatment using T-maze, Morris water maze, and open field tests. The results showed that the extract was safe up to 4000 mg/kg. AlCl3 significantly impaired spatial learning, memory and locomotor activity as observed with the AlCl3-induced, untreated group. However, pretreatment with Artocarpus heterophyllus seed extract significantly (p < 0.05) improved the motor activity, exploration and reduced anxiety-like behaviour dose-dependently. These findings indicate that Artocarpus heterophyllus seed ethanol extract ameliorates aluminum chloride–associated behavioural and cognitive deficits in mice and warrant further mechanistic investigations.