Integrative network and structural analysis of Pinus derived phytosterols in diabetes associated pathways

Diabetes mellitus, a chronic metabolic disorder with its prevalence rising rapidly has emerged as major global health concern. Although Pinus species are abundant in bioactive phytosterols, little is known about how these compounds interact molecularly with targets linked to diabetes. The interaction potential of two phytosterols derived from Pinus, β-sitosterol and 24-nor-cholest-5,22E-dien-3β-ol, with important endocrine-related protein targets found in diabetes was examined in this study using an integrative computational workflow. ESR1, AR, SHBG, and CYP17A1 were found to be central nodes in pathways linked to endocrine resistance by network pharmacology analysis. Favorable binding interactions were predicted by molecular docking, especially with CYP17A1 and SHBG, whereas ESR1 and AR showed moderate affinities. The structural stability of representative protein-ligand complexes was further reinforced by Protein flexibility analysis, which also offered molecular-level understanding of their behaviour. Using publicly available biological databases and bioinformatics platforms, network pharmacology and protein-protein interaction studies were conducted before functional enrichment analysis was conducted to identify significant biological pathways. Molecular docking was performed using SwissDock to evaluate the interaction energies and binding modalities between specific protein targets and phytosterols. Protein-ligand complexes' flexibility and behaviour were assessed using the CABS-flex 2.0 web server. Structural visualization and interaction analysis were conducted using standard molecular graphics and trajectory analysis tools.

The online version contains supplementary material available at 10.1007/s40203-026-00682-9.