Investigating the Phytochemical Constituents, Anti-Inflammatory, and Neuropharmacological Activities of Podocarpus neriifolius Leaves Through FT-IR, GC-MS, Experimental Studies, Molecular Docking, and Molecular Dynamics Simulations

Abstract

Podocarpus neriifolius, a widely distributed medicinal plant in South and Southeast Asia, has traditionally been used to treat rheumatism and joint pain. This study aimed to investigate the phytochemical profile and therapeutic potential of the ethanolic leaf extract of P. neriifolius (EEPN) using integrated in vitro, in vivo, and in silico approaches. Phytochemical analysis via FT-IR and GC-MS revealed the presence of steroidal glycosides, flavonoids, alkenes, aliphatic compounds, steroids, saponins, and other glycosides. In a COX inhibition assay, EEPN demonstrated notable in vitro anti-inflammatory effects, further validated in a mouse paw edema test. In Swiss albino mice, EEPN (200 and 400 mg/kg) showed increased head dipping in HBT (43.4 +/- 1.14 and 69.2 +/- 1.22), where the standard showed (57.5 +/- 1.01), and improved open-arm entries and time in EPM (260.3 and 280.6 s) compared to the standard (245.2 s). EEPN produced a dose-dependent sedative effect both in HCT and OFT. Furthermore, EEPN significantly lowered immobility time in the tail suspension and forced swimming tests, demonstrating its antidepressant effects. According to molecular docking studies, the phytochemicals in EEPN showed a strong affinity for binding to important drug target proteins linked to inflammation, anxiety, and depression. The EEPN had binding affinities of -6.6, -5.4, and -10 kcal/mol with COX2, GABAA, and the serotonin transporter, respectively. Protein-ligand complex stability was validated through molecular dynamics simulations analysis. The pharmacokinetic and safety profile of the compounds in ADMET analysis showed druggable qualities within acceptable ranges, implying the possibility as potential medications in the future. However, further research is necessary to ascertain whether P. neriifolius leaves can be utilized as a therapeutic agent.