Exploration of the potential mechanism of Duhuo Jisheng Decoction in osteoarthritis treatment by using network pharmacology and molecular dynamics simulation

In this study, the active ingredients of 15 Chinese herbal medicines of Duhuo Jisheng Decoction and their corresponding targets were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The microarray data of Osteoarthritis (OA) were obtained through the GEO database for differential analysis and then a drug target-OA-related gene protein-protein interaction (PPI) network was established. The potential targets of Duhuo Jisheng Decoction in the treatment of OA were acquired by intersecting the OA-associated genes with the target genes of active ingredients. Random walk with restart (RWR) analysis of PPI networks was performed using potential targets as seed, and the top 50 genes of affinity coefficients were used as key action genes of Duhuo Jisheng Decoction in the treatment of OA. A drug-active ingredient-gene interaction network was established. AKT1, a key target of Duhuo Jisheng Decoction in the treatment of OA, was obtained by topological analysis of the gene interaction network. Molecular docking and molecular dynamics verified the binding of AKT1 to its corresponding drug active ingredients. CETSA assay demonstrated that the combination of luteolin and AKT1 increased the stability of AKT1, and the combination efficiency was high. In conclusion, the molecular mechanism of Duhuo Jisheng Decoction in treating OA featured by multiple components, targets, and pathways had been further investigated in this study, which is of significance for discovering as well as developing new drugs for this disease. The findings can also offer personalized diagnosis and treatment strategies for patients with OA in clinical practice. [GRAPHICS] .