Potential Mechanisms Underlying the Therapeutic Roles of Gancao fuzi Decoction in Cold-dampness Obstruction Syndrome-type Knee Osteoarthritis

Background: The key active components and potential molecular mechanism of Gancao Fuzi decoction (GFD) in the treatment of cold-dampness obstruction-type knee osteoarthritis (KOA) remain unclear. Objective: To explore the mechanism of GFD in the treatment of cold-dampness obstruction syndrome-type KOA by network pharmacology. Methods: The potential active components and targets of the four herbs in GFD (Fuzi, Guizhi, Baizhu, and Gancao) were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The targets of KOA were obtained with the Comparative Toxicogenomics Database (CTD), the GeneCards database, and the DisGeNET database, and the common targets of the drugs and disease were ultimately obtained. Cytoscape (v.3.7.1) was used to draw the active component-target network, and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) (v.11.0) database was used to construct the protein interaction network. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the intersecting targets. Results: A total of 102 potential active components and 208 targets of GFD in the treatment of cold-dampness obstruction syndrome-type KOA were screened. GFD treatment was found to be closely related to many inflammatory signalling pathways in the treatment of KOA. Conclusion: The effect of GFD on cold-dampness obstruction syndrome-type KOA is mediated by multicomponent, multitarget, and multichannel mechanisms, which provides the basis for further experimental study of its pharmacodynamic material basis and mechanism.