Computational Chemistry, Network Pharmacology, and Computational Biology Integrated with Experimental Assays for Determining the Anti-Diabetic and Kidney-Protecting Effects of Rutoside (rutin) Molecule

Diabetic Nephropathy (DN), a major complication of diabetes mellitus, is a leading cause of end-stage renal disease worldwide. This study explores the therapeutic potential of rutoside (rutin) in combating DN using a streptozotocin (STZ)-induced diabetic rat model. Additionally, we conducted mechanistic evaluations to elucidate the underlying pathways involved in rutin-mediated renoprotection, focusing on network pharmacological analysis and molecular interactions through in silico molecular docking studies, and experimental validation of its antioxidant and anti-inflammatory effects. A network pharmacological approach was used with the initial screening of the pharmacokinetic properties of rutin and toxicity evaluation, which indicated low GI absorption with a bioavailability value of 0.17 and no major toxicity associated with the rutin molecule. Target prediction revealed 97 biological targets of rutin and 858 targets of diabetic nephropathy; among these 35 targets were found to be common between rutin and diabetic nephropathy, and these and KEGG enrichment pathways was also carried out to demonstrate the involvement of different genes, and their functions, besides the signalling pathways, and how these to identify key molecular interactions and the involved amino acid residues of the targets. Rutin treatment exhibited a considerable hypoglycaemic index in comparison to the diabetic group. Treatment with rutin also led to a substantial reduction in raised levels of the cytokines involved in inflammation. The antioxidant enzymes were effectively brought to appropriate levels and under control by rutin treatment. Oral administration of rutin our study provided evidence based on bioinformatics, network pharmacology, as well as experimental data about the protective effects of rutin in diabetic nephropathy, and as such, rutin can be a potential drug candidate for future research in this field.