Attenuation of morphine-induced memory deficits by Celosia cristata flower extract: Behavioral and computational insights.

Prolonged opioid use is associated with many complications, including significant memory deficits. Celosia cristata, a traditionally used medicinal plant, exhibits diverse pharmacological activities; however, its neurocognitive potential remains unexplored. This study is designed to investigate the effects of the methanolic extract of C. cristata (MECC) on morphine-induced cognitive impairment in mice. Phytochemical profiling using GC-MS identified 21 bioactive compounds, including fatty acid derivatives, phenolics, and alkaloids. Following behavioral screening to exclude the anxiety- or depression-related bias, behaviorally naive mice were subjected to the Morris Water Maze Test (MWMT) and Novel Object Recognition Test (NORT) to evaluate the learning and memory performance. MECC-treated mice exhibited significantly greater spending time in the targeted quadrant of the MWM apparatus (p < 0.05) compared to the morphine-only control, indicating enhanced spatial memory. On the other hand, in NORT, MECC (250 and 500 mg/kg b.w. of mice) increased the exploration time around the novel object by 1.5-2-fold relative to morphine-only mice (p < 0.05), demonstrating dose-dependent improvement of the recognition memory. In-silico analyses identified methyl 9-cis,11-trans-octadecadienoate, 13-octadecenoic acid methyl ester, and tetradecanoic acid 10,13-dimethyl methyl ester as potential neuroactive constituents with strong affinities for AMPA-R and NMDA-R. These compounds also fulfilled key ADMET criteria, including BBB and Caco-2 permeability, and non-mutagenicity. Hence, the ameliorating effects of MECC may be associated with the presence of these compounds, while the docking results provide preliminary mechanistic hypotheses suggesting possible modulation of glutamatergic receptor pathways that warrant further experimental validation. To our knowledge, this is the first report demonstrating the memory-enhancing effects of MECC. Further studies are warranted to isolate the active compounds and elucidate their molecular mechanisms for potential therapeutic development.