Md Azzaat Ahsanie Lokman, Md. Liakot Ali, Qurratul Ain Sadia, Saad Ahmed Sami, Md Ashraful Alam, Nawreen Monir Proma, Mohammad Rashedul Islam, Mohammed Kamrul Hossain
ABSTRACT Artocarpus chama , a widely known fruit‐bearing plant in Asia and locally referred to as Chapalish in Bangladesh, has been traditionally used for various medicinal purposes. However, its neuropharmacological potential remains largely unexplored in current scientific literature. This research aims to investigate the in vitro antioxidant and in vivo neuropharmacological properties of the methanolic extract of A. chama leaves (MEAC) along with its n‐hexane (NHAC) and ethyl acetate (EAAC) fractions. The DPPH assay revealed strong antioxidant activity, with MEAC displaying an IC₅₀ of 24.30 ± 1.04 μg/mL, while NHAC and EAAC showed IC₅₀ values of 45.18 ± 2.4 μg/mL and 30.46 ± 1.15 μg/mL, respectively. In in vivo models, MEAC, NHAC, and EAAC exhibited significant anxiolytic effects in the elevated plus maze and hole‐board test at both doses (200 and 400 mg/kg). Notable sedative effects were observed in the open field test at 200 and 400 mg/kg doses, but only in the hole cross test at the 400 mg/kg dose. Additionally, all three extracts demonstrated significant antidepressant activity in behavioral despair tests at all investigated doses. GC–MS analysis identified a total of 40 phytoconstituents, several of which exhibited notable binding affinities to key drug target proteins involved in oxidative stress, anxiety, sedation, and depression, as shown through molecular docking studies. Furthermore, ADMET predictions supported their drug‐likeness and favorable pharmacokinetic and toxicity profiles. These findings suggest that A. chama leaves may serve as a promising source of bioactive compounds with neuropharmacological potential. However, further extensive studies are warranted.