<i>In Silico</i> and Network Pharmacology Approach for Mechanistic Exploration of <i>Rhododendron arboreum</i> Sm. Leaf in Nonalcoholic Fatty Liver Disease

Rhododendron arboreum Sm. (Burans) (family Ericaceae) has traditionally been used in Indian medicine to treat liver disorders. However, its mechanism against non-alcoholic fatty liver disease (NAFLD) remains elusive. This study utilized in silico methods — network pharmacology, ADMET prediction, molecular docking and molecular dynamics (MD) simulations for mechanistic exploration of Rhododendron arboreum leaves (RAL) in NAFLD. Bioactive compounds were sourced from open databases and assessed for drug-likeness and ADMET profiles. Network pharmacology identified key protein interactions using the STRING platform. GO analysis identified galactose metabolism, pentose and glucuronate interconversions and other processes in treating NAFLD. Molecular docking revealed that amyrin and pectolinarigenin had the highest binding affinities, with dock scores of −12.2 kcal/mol (AKR1C3-amyrin), −10.2 kcal/mol (PI3K-amyrin), −9.3 kcal/mol (AKR1C3-pectolinarigenin) and −9.6 kcal/mol (HSD17B1-pectolinarigenin). MD simulations, focusing on RMSD and RMSF analyses, confirmed the stability of these interactions. The RMSD graphs revealed stable binding pocket regions, highlighted in pink. Notably, the RMSF values for PHE (B:306) in the AKR1C3-amyrin complex and ARG (A:294) in the PI3K-amyrin interaction were 0.623 nm and 0.1586 nm, respectively, indicating stable ligand interactions. Our findings holistically clarify toxicity data, potential bioactives targets and molecular mechanisms of RAL against NAFLD, paving the way for future research.