Development of Phytoactive-Based Therapeutics from Cyamopsis Tetragonoloba for Targeting Inflammation and Neuroinflammation: A Computational Approach Integrating Receptor Interaction and Formulation Strategies

Abstract

This study presents a comprehensive in silico evaluation of phytochemicals derived from Cyamopsis tetragonoloba (guar), aimed at assessing their pharmacokinetic profiles, therapeutic potential, and formulation feasibility. A multifaceted computational approach was employed, incorporating ADME profiling, network pharmacology, molecular docking, molecular dynamics simulations, and lipid-based formulation modeling. ADME analysis indicated that all selected compounds conformed to major drug-likeness criteria and lacked PAINS alerts, though most exhibited low gastrointestinal absorption and poor solubility. Network pharmacology identified AKT1 as a key hub protein associated with inflammation, alongside other notable targets such as PPARG and STAT3, suggesting potential for multi-targeted anti-inflammatory action. Molecular docking revealed strong binding affinities between lead compounds—particularly quercetin, kaempferol, and beta-sitosterol—and target proteins, with stable interactions confirmed through molecular dynamics simulations. Kaempferol, in particular, demonstrated minimal structural deviation, highlighting its binding stability. Free energy landscape analyses further supported the formation of energetically favorable protein-ligand complexes. To address solubility limitations, in silico compatibility studies with lipid-based excipients indicated that quercetin forms stable interactions with phospholipids and fatty acids, supporting the feasibility of lipid-based delivery systems for improved bioavailability.

Overall, the findings highlight the therapeutic promise of Cyamopsis tetragonoloba phytochemicals and propose viable strategies for overcoming pharmacokinetic challenges. This integrative in silico approach not only accelerates early-stage drug discovery but also lays a strong foundation for future experimental validation and clinical development of plant-based anti-inflammatory therapeutics.