Amelioration of nicotine-induced neurobehavioral deficits by methanolic extracts of Drymaria cordata (L.) Willd. ex Schult.: an in silico and in vivo study
摘要
Drymaria cordata (L.) Willd. ex Schult. (family: Caryophyllaceae) is an ethnomedicinal plant traditionally used by the tribes of the Dima Hasao district of Assam to treat fever, cough, cold, asthma, headache, sinusitis, wounds, joint pain, stomach ulcers, sleep disturbances, hallucinations, and inflammatory conditions. The present study investigated the neuroprotective potential of the methanolic extract of D. cordata (DCME) against nicotine-induced neurotoxicity using both in silico and in vivo approaches. GC–MS profiling identified 49 phytocompounds, indicating the chemical diversity of the extract. Among these, 11 compounds fulfilled SwissADME drug-likeness criteria, and 10 showed acceptable toxicity profiles in ProTox-3. PASS analysis predicted antioxidant, cytoprotective, anti-inflammatory, and neuroprotective properties for the selected phytoconstituents. Molecular docking was performed against four neurorelevant targets: KcsA potassium channel (4UUJ), GABAA β3 receptor (4COF), 5-HT3 receptor (4PIR), and NMDA GluN1b–2B receptor (7TE6). Docking validation yielded RMSD values below 2.0 Å. Among the prioritized ligands, 13-hexyloxacyclotridec-10-en-2-one exhibited the most consistent binding across all targets. In vivo evaluation using Swiss albino mice showed that nicotine administration (14.69 mg/kg) induced anxiety-like behavior, depression-like behavior, locomotor suppression, and memory impairment (p < 0.001). Treatment with DCME (200 and 500 mg/kg) significantly alleviated these effects. The higher dose improved behavioral outcomes in the Elevated Plus Maze, Open Field Test, Forced Swim Test, and Morris Water Maze test (p < 0.001). DCME also reduced lipid peroxidation and restored antioxidant and cholinergic enzyme activities (p < 0.01). Overall, these findings support the traditional use of D. cordata and highlight its potential as a neuroprotective ethnomedicinal agent.