Exploring the Anti-psoriatic Potential of Bioactive Compounds from <i>Rhinacanthus nasutus</i> and <i>Solanum nigrum</i> Leaves through Molecular Docking and Dynamics Simulation Studies

Background: Ethnomedicinal plants have long been recognized for their therapeutic potential in managing inflammatory and skin-related disorders, with several species demonstrating promising bioactivity through both traditional use and modern pharmacological investigations. Aim: To investigate the anti-psoriatic potential of bioactive compounds from Rhinacanthus nasutus and Solanum nigrum leaves through molecular docking and dynamics simulation studies. Methods:We investigated two ethnomedicinal plants, R. nasutus and S. nigrum, which have been used traditionally for healing skin diseases that mimic psoriasis. A parallel in silico study was performed for assessing the activity of their bioactive molecules (Rhinacanthin D and Trihydroxyflavone) on molecular targets linked with psoriasis such as Tyk2, PDE4D and S1P1 Receptor (S1P1R). Molecular docking studies were conducted using Auto Dock Vina, followed by 100 ns molecular dynamics simulations using GROMACS to verify the stability of ligand-protein complexes. Results: Analysis of the binding energies indicated favorable binding for both compounds, with rhinacanthin D showing high favorable interactions with these key inflammatory molecules. Molecular dynamics simulations confirmed the stability of the ligand-protein complexes, as evidenced by Root-Mean-Square Deviation (RMSD), Fluctuation (RMSF), and hydrogen bond occupancy analyses. The Binding Free Energy (BFE) results further corroborated the strength of interaction, especially for rhinacanthin D-included complexes. Conclusion: The findings are indicative of the potential use of R. nasutus and S. nigrum compounds as lead compounds against anti-psoriatic agents, thus providing a scientific foundation for the traditional use of these plants for treatment of psoriasis. However, comprehensive in vitro and in vivo studies are essential to validate these computational insights and translate them into viable therapeutic applications. Major Findings: Rhinacanthin D demonstrated strong and stable interactions with key psoriasis-related targets (Tyk2, PDE4D, and S1P1R) across docking and molecular dynamics analyses. The computational outcomes support its potential as a lead anti-psoriatic compound, warranting further experimental validation