In silico evaluation of berberine and silymarin against metabolic targets: a rationale for OMICS technology-based...

Berberine and silymarin are phytochemicals with established pleiotropic effects across glucose, lipid, and inflammatory pathways, making them promising candidates for managing metabolic disorders such as type 2 diabetes mellitus (T2DM) and dyslipidaemia. However, their clinical translation is hindered by poor solubility, low permeability, and metabolic instability. This study aimed to evaluate the pharmacokinetic and pharmacodynamic profiles of berberine and silymarin using in silico tools and propose a rational design for an OMICS technology-based co-formulation to enhance their therapeutic potential. Comprehensive in silico analyses were performed, including molecular docking against DPP4, PTP1B, PCSK9, and P38MAPK, ADMET profiling, CYP450 interaction prediction, toxicity screening, and canonical SMILES-based structural assessment. Berberine showed good GI and BBB permeability with strong target binding (- 7.1 to - 8.0 kcal/mol) but presented liabilities including P-gp efflux and CYP inhibition. Silymarin exhibited stronger docking scores (up to - 9.0 kcal/mol) and favourable safety but limited permeability. Their complementary profiles support co-formulation. Findings support the development of an OMICS technology-based lipid-protein encapsulated formulation to overcome pharmacokinetic barriers and enhance synergistic efficacy. This approach holds promise for optimized multi-target management of T2DM and related metabolic disorders.