Computational Evaluation of Phytochemicals from Oxalis corniculata and Oxalis latifolia as Potential Modulators of the Human Pregnane X Receptor
2025-12-30
Ram Lal (Swagat) Shrestha, Shiva M.C., Ashika Tamang, Manila Poudel, Sujan Dhital, Nirmal Parajuli, Safal Adhikari, Aakar Shrestha, Timila Shrestha, Samjhana Bharati, Binita Maharjan, Bishnu Prasad Marasini, Jhashanath Adhikari Subin
The genus Oxalis is known for its diverse medicinal properties, offering phytochemicals with therapeutic applications. This study investigates the potential of these compounds as modulators of human pregnane X receptor (hPXR), a key regulator of genes involved in drug metabolism and detoxification. Its activation affects the body’s response to foreign chemicals (xenobiotics), including drugs, influencing drug-drug interactions, pharmacokinetics, and toxicity. Using molecular docking techniques, 36 compounds selected from Oxalis corniculata and Oxalis latifolia were evaluated for their interaction with hPXR. The phytocomponents, squalene, diosmetin-7-O-beta-D-glucopyranoside, apigenin-7-O-glucoside, rhapontin, and luteolin-7-O-glucoside exhibited stronger binding affinities compared to the receptor's native ligand, suggesting a better role in modulating hPXR activity. Protein-ligand interaction analysis of five ligands revealed hydrophobic, hydrogen bonds, and salt bridges, with key residues, TRP299, HIS407, LEU209, LEU411 and PHE288, stabilizing ligand binding. ADMET analysis predicted favorable drug-like properties for these compounds, supporting their further development. Squalene, diosmetin-7-O-beta-D-glucopyranoside, and apigenin-7-O-glucoside were identified as promising candidates due to their strong binding and acceptable pharmacokinetic profiles. This computational evaluation provides insights into Oxalis phytochemicals as potential natural modulators of hPXR, with implications for therapeutic interventions and future experimental studies.