五苓散治疗骨关节炎潜在分子机制及网络药理学与分子对接.

BACKGROUND: Wuling power has an effective effect in the clinical treatment of knee arthritis, but its pharmacological effects, but its molecular mechanisms and drug active components are not yet clear. OBJECTIVE: Based on the network pharmacology method, the potential molecular mechanism of Wuling powder in the treatment of osteoarthritis was explored, and the role of these molecules and related signaling pathways was elaborated, providing a theoretical basis for further extraction of key drug compounds. METHODS: TCMSP was used to screen the active components and corresponding targets of Wuling powder, and Gene Cards, OMIM and DigSee disease databases were integrated to obtain the related targets of osteoarthritis. The potential targets of Wuling powder in the treatment of osteoarthritis were obtained by mapping and intersection on the Venny platform. The network of “single drug-active component-interaction target” and protein-protein interaction network of Wuling powder in the treatment of osteoarthritis were constructed by using the software of Cytoscape, and the functional enrichment analysis of GO and the enrichment analysis of KEGG pathway of Wuling powder in the treatment of osteoarthritis were carried out by using David database. Finally, the key active components and key targets of Wuling powder were verified through molecular docking by using PyMOL and other software. RESULTS AND CONCLUSION: A total of 52 active ingredients including β-sitosterol, catechin and taxifolin were screened. The protein-protein interaction analysis indicated that there were 26 key targets of Wuling powder in the treatment of osteoarthritis, including estrogen receptor 1 (ESR1), which can promote the proliferation of chondrocytes and inhibit the expression of related inflammatory cytokines, tumor protein p53 (tumor protein), which is involved in the inflammatory reaction of osteoarthritis p53, and ubiquitin ligase CUL3 (cullin3) that mediates apoptosis. The results of molecular docking showed that catechin with the lowest affinity and NTRK1 had a good molecular docking, indicating that the predicted key active components of Wuling powder have a good binding activity with the key targets of osteoarthritis treatment. There were 709 GO items in total, including 649 biological processes, 22 cell components and 38 molecular functions, which are mainly involved in the response to estrogen, inflammation and lipopolysaccharide. KEGG pathway enrichment analysis showed that the related pathways of key protein modules included AGE-RAGE signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, p53 signaling pathway, and estrogen signaling pathway, which are involved in the process of oxidative stress, inflammatory response and apoptosis of chondrocytes. The results showed that the active compounds β-sitosterol, catechin, taxifolin and hederagenin in Wuling powder could regulate relevant signaling pathways by regulating the expression of ESR1, TP53, CUL3 and MCM2 related protein targets, which can slow down the apoptosis of chondrocytes, strengthen the proliferation and repair of chondrocytes, and reduce the inflammatory response. [ABSTRACT FROM AUTHOR]