Unraveling the Multi-Target Mechanisms of Cosmos sulphureus in Diabetic Neuropathy Through Network Pharmacology

AbstractDiabetic neuropathy is a common and severe complication of diabetes mellitus characterizedby progressive nerve damage resulting from chronic hyperglycemia, oxidative stress,inflammation, and metabolic dysfunction. The present study aimed to investigate thetherapeutic potential and underlying molecular mechanisms of six phytoconstituents ofCosmos sulphureus—oleic acid, arachidic acid, linolenic acid, linoleic acid, stearic acid, andpalmitic acid—against diabetic neuropathy using a network pharmacology approach. Thepotential targets of these phytoconstituents were identified and intersected with diabeticneuropathy-related genes to obtain common therapeutic targets. Protein–protein interactionnetwork analysis, Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomespathway analysis, and OMIM disease enrichment were performed to elucidate the biologicalsignificance of the identified targets. The results obtained revealed that the common targetswere primarily involved in lipid metabolism, inflammatory responses, oxidative stressregulation, apoptosis, and cellular survival processes. GO enrichment analysis highlightedsignificant roles in receptor-mediated signaling, mitochondrial function, and metabolicregulation, while KEGG analysis identified pathways related to insulin resistance, PPARsignaling, Toll-like receptor signaling, and lipid metabolism. OMIM disease enrichmentdemonstrated strong associations with diabetes, type 2 diabetes mellitus, obesity, and othermetabolic disorders. These findings suggest that the selected phytoconstituents of Cosmossulphureus exert therapeutic effects through a multi-component, multi-target, and multi-pathway mechanism by modulating oxidative stress, inflammation, apoptosis, and metabolicdysfunction. The study provides a scientific basis for the potential use of thesephytoconstituents as natural therapeutic candidates for the prevention and management ofdiabetic neuropathy and supports further experimental validation.