The paper aimed to investigate the therapeutic effect of eleutheroside E (EE) on knee osteoarthritis and analyze the mechanisms of EE,to clarify the interaction sites and binding modes of EE and MMPs.The ACLT method was adopt to establish a rabbit model of knee osteoarthritis,and EE was given by injection into the joint cavity for therapeutic intervention.Further using molecular docking technology and molecular dynamics methods to analyze the interaction sites and binding modes of EE with MMPs.These results indicated that EE could significantly improve inflammatory cell infiltration,fibrous tissue hyperplasia and cartilage surface destruction in osteoarthritis,and reduce the content levels of inflammatory factors (IL-1β and PGE₂) and MMP-3 and MMP-9 in joint fluid.In addition,molecular docking and molecular dynamics experiments found that EE ligands could bind to the grooves of the catalytic sites of MMP-3 and MMP-9,and the multiple hydroxyl groups on the sugar ring of EE could form hydrogen bonds with multiple amino acids in the MMP-3 and MMP-9 receptors,which play an important role in the binding of ligands.The study lays a foundation for the development of novel MMPs inhibitors with the mother nucleus of lignan glycosides and candidate therapeutic drugs for osteoarthritis from natural sources.