Bioinformatics-based analysis of Cordyceps Sinensis in the treatment of diabetic nephropathy-associated depression

Background Diabetic nephropathy (DN) and depression exhibit complex pathological association; yet western medicine shows limited efficacy with notable side effects. Cordyceps sinensis (CS), a traditional Chinese medicine, demonstrates advantages in improving renal function and regulating neuroimmunity, but its mechanism for treating DN with depression remains unclear. Methods Active components of CS were screened via TCMSP, disease-related targets were identified from GeneCards and OMIM, and potential targets were determined by intersection analysis. PPI network, GO/KEGG enrichment analyses, and "drug-component-target-pathway" network were constructed. Molecular docking and molecular dynamics simulations were employed to verify binding affinity and stability. Results Seven active ingredients (e.g.β-sitosterol, ergosterol) and 40 key targets were identified, with PIK3CA, AKT1, and MAPK1 as core hubs. CS primarily modulated PI3K-Akt, MAPK-ERK, and androgen receptor pathways. Molecular docking revealed binding energies < -7.0 kcal/mol, and MD simulations confirmed complex stability within 50 ns. Conclusion CS treats DN with depression via multi-component and multi-target synergism, targeting PIK3CA/AKT1/MAPK1 to regulate signaling pathways, thereby offering mechanistic molecular bases for clinical intervention.