Multitarget Neuropharmacological Actions of Drimycarpus racemosus Hook. f. GC–MS‐Guided In Vivo and In Silico Evidence of Anxiolytic and Antidepressant Potential
TL;DR
The combined in vivo and in silico findings indicate that D. racemosus exerts multitarget neuropharmacological effects, primarily through modulation of GABAergic and serotonergic systems, which highlight the phytochemical richness and therapeutic promise of MEDR as a potential source for developing safe, plant‐based neurotherapeutics for anxiety and depression.
Abstract
Anxiety and depression are significant neurological disorders with limited treatment efficacy and notable side effects associated with conventional synthetic drugs. This study investigated the anxiolytic and antidepressant potential of the methanolic leaf extract of Drimycarpus racemosus Hook. f. (MEDR) using both in vivo behavioral models and in silico molecular docking approaches. GC–MS analysis of MEDR identified 39 phytochemical constituents, including bioactive terpenoids, phenolic compounds, and fatty acid esters. In vivo experiments were conducted (n = 5 per group) on Swiss albino mice randomly divided into control, standard (diazepam 1 mg/kg), and treatment groups receiving MEDR (200 and 400 mg/kg) using the elevated plus maze (EPM), hole‐board test (HBT), light–dark box (LDB), and forced swim test (FST). MEDR exhibited significant dose‐dependent effects. At 400 mg/kg, MEDR significantly increased time spent in the open arms of the EPM by approximately 89% (140.0 ± 1.79 s vs. 74.2 ± 2.71 s in control, ∗p < 0.05) and number of open‐arm entries (17.2 ± 1.43 vs. 10.4 ± 1.57) while markedly reducing immobility time in the FST by ~44% (102.2 ± 1.16 s vs. 182.6 ± 1.94 s in control, ∗p < 0.05). These effects were comparable to the standard drug diazepam (1 mg/kg). Molecular docking studies against the potassium channel (PDB ID: 4UUJ), GABAA receptor (PDB ID: 6X3X), and human serotonin transporter (hSERT, PDB ID: 5I6X) revealed that β‐sitosterol acetate and 2‐[4‐cyclohexylbutanoylamino]‐3‐chloro‐1,4‐naphthoquinone exhibited higher binding affinities than diazepam across all three targets. The combined in vivo and in silico findings indicate that D. racemosus exerts multitarget neuropharmacological effects, primarily through modulation of GABAergic and serotonergic systems. These results highlight the phytochemical richness and therapeutic promise of MEDR as a potential source for developing safe, plant‐based neurotherapeutics for anxiety and depression.