Phytochemical Profiling, Computational Analysis and Molecular Docking of <i>Moringa Oleifera</i> Seed Constituents Targeting the Serotonin 1A (5-HT1A) Receptor, Insights into Antidepressant Potential

Native to tropical and subtropical regions, Moringa oleifera, often known as Moringa, is a member of the Moringaceae family. It can be found in Northwest India and Pakistan’s sub-Himalayan regions. The phytochemical makeup of the methanolic extracts of M. oleifera seeds (Met-Ext-M.O.) was examined using gas chromatography-mass spectroscopy (GC-MS) analysis, followed by molecular docking studies for the determination of the most potent ligands. A UV spectrophotometer was used to analyze the extracts for in vitro DPPH scavenging activity at different doses (1000 [Formula: see text]g/mL, 500 [Formula: see text]g/mL, 250 [Formula: see text]g/mL, 125 [Formula: see text]g/mL, 62.5 [Formula: see text]g/mL and 31.05 [Formula: see text]g/mL), with ascorbic acid serving as a reference standard. The extract was further assessed using two in vivo antidepressant tests: The tail suspension test (TST) and the forced swim test (FST). Mice were administered 125 mg/kg and 250 mg/kg body weight of M. Oleifera Met-Ext. In the meantime, the standard group received an oral imipramine dosage of 10 mg/kg/day. An hour before the test began, imipramine and plant extracts were administered orally. The molecular docking study revealed that certain phytoconstituents (50 phytochemicals) identified by GC-MS analysis are capable of binding serotonin 1A receptor with favorable affinity, potentially, ensuring an interaction with neuroreceptor systems, which mediate mood regulation. GC-MS profiling provided a preliminary characterization of the phytochemical components of M. oleiferaseed extract, but some of the compounds identified, e.g. those based on phthalates, could have been due to environmental or laboratory contamination and therefore were handled with care in the context of their possible biological activity. These phytochemicals were grouped based on their molecular weight at various retention periods, and constituents like Benzo[c]phenanthrene, 5-methyl showed the best binding affinity (−8.5 kcal/mol), Benzo[1,2-b:5,4-b[Formula: see text]]difuran-4,8-dione and 1,3,5-Triazin-2(1H)-one derivatives with Serotonin-bound Serotonin 1A receptor-Gi protein complex (7e2y) by molecular docking studies, suggesting potential for antidepressant effects and novel therapeutic agents. M. Oleifera Met-Ext also showed a great in vitro antioxidant activity, which can lead to neuroprotective effects, but this antioxidative activity cannot be directly related to antidepressant effects. Compared to ascorbic acid (91 ± 0.5; IC[Formula: see text] 30 [Formula: see text]g/mL), Met-Ext-M.O. at 1000 [Formula: see text]g/mL (82 ± 1.5***; IC[Formula: see text] 90 [Formula: see text]g/mL) considerably reduced the percentage suppression of DPPH free radicals. Consequently, it was discovered that the extract was a potent antioxidant that also performed well in vivo. Mice administered imipramine and Met-Ext-M.O. in both test models had shorter durations of immobility on days 1, 7 and 14 of the experiment compared to the control group. In contrast to the normal group, which experienced 197.76 ± 4.42 on day 1, 199.08 ± 2.29 on day 7 and 200.28 ± 3.17 on day 14, the immobility period for 125 mg/kg was 131.63 ± 3.79, 117.85 ± 2.47 and 107.09 ± 2.24 on days 1, 7 and 14. The immobility period for 250 mg/kg was 112.19 ± 2.69 on days 1, 7 and 14, 105.49 ± 2.55 and 90.21 ± 2.21 on day 14, respectively. Days 1, 7 and 14 following imipramine injection showed a significant reduction in immobility time (86.64 ± 1.66, 72.35 ± 1.75 and 54.75 ± 1.69). In vivo behavioral studies (TST and FST) demonstrated that there was a significant decrease in immobility time, exhibiting antidepressant-like effects in mice. These findings, when allied, suggest that these behavioral effects can possibly be explained by the active presence of phytochemicals, but there is still a need to conduct further mechanistic and clinical studies to determine a definite antidepressant mechanism. These effects, which could have a major impact on both in vitro and in vivoresearch, could be caused by physiologically active phytonutrients in the plants.