Exploring the Potential Mechanisms of Zuo Gui Pill for the Treatment of Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking Techniques

Background: Zuo Gui pill (ZGP) is a herbal compound formulation used to treat knee osteoarthritis (KOA), but its underlying mechanisms are still unclear. This study aimed to initially elucidate the molecular mechanisms of ZGP in treating KOA using network pharmacology and molecular docking techniques. Methods: We collected information on the drug compounds and targets from TCMSP, HERB, BATMANTCM, and UniProt databases, as well as the KOA-related targets from DisGeNET, GeneCards, OMIM, and GEO databases. Afterward, we obtained the hub targets of ZGP and KOA. The biological processes and major pathways of the hub targets were analyzed by GO and KEGG, and three networks were constructed to illustrate the mechanisms of ZGP for the treatment of KOA. Finally, molecular docking was carried out to verify the binding of the main compounds to the key targets. Results: Through the network pharmacological analysis, we screened important compounds in ZGP, such as quercetin, kaempferol, wogonin, isorhamnetin, and 138 hub targets, including PTGS2, NOS3, AKT1, MAPK1, which are enriched in PI3K-Akt, MAPK, TNF, IL-17, HIF-1, and other signaling pathways. The molecular docking results showed that the main compounds and key targets have high affinity, which further demonstrated the molecular mechanisms and provided a basis for the clinical application of ZGP. Conclusion: This study illustrates the specific mechanisms of ZGP in the treatment of KOA using network pharmacology and molecular docking techniques, which lays the foundation for further research on its pharmacological mechanisms.