Objective To explore the effect and mechanism of icariin in improving knee osteoarthritis (KOA) in rats with kidney deficiency and blood stasis based on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods A total of 60 female SD rats were randomly divided into control group, model group, positive control [Xianling Gubao Capsules (仙灵骨葆胶囊, 270 mg/kg)] group and icariin low-, medium-, high-dose (40, 100, 200 mg/kg) groups, with 10 rats in each group. Except for the control group, the other groups were prepared with a combination of “ovariectomy method + hydrocortisone combined with adrenaline method + modified Hulth method” to establish a kidney deficiency and blood stasis KOA rat model. After successful modeling, each group was administered ig continuously for four weeks. The joint inflammation score and joint swelling degree of rats were measured at 0, 1, 2, 3, and 4 weeks after administration. After administration, the levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and IL-10 in serum were detected by ELISA. Hematoxylin-eosin (HE) staining was used to observe pathological changes in knee cartilage. Western blotting was used to detect the expressions of TLR4, myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB (IκB), p-IκB, NF-κB p65 and p-NF-κB p65 proteins in cartilage tissue. Results Compared with control group, the joint inflammation score and joint swelling degree of rats in model group were significantly increased (P < 0.001), the levels of IL-1β, IL-6, TNF-α in serum were significantly increased (P < 0.001), and the level of IL-10 was significantly decreased (P < 0.001). The pathological damage of cartilage tissue was obvious, and the protein expression levels of TLR4, MyD88, p-IκB, p-NF-κB p65 in cartilage tissue were significantly increased (P < 0.05, 0.01, 0.001). Compared with model group, the positive control group and icariin medium-, high-dose groups showed varying degrees of improvement in the above indicators, while some indicators in icariin low-dose group showed an improvement trend. Conclusion Icariin could improve joint inflammation and cartilage damage in KOA rats with kidney deficiency and blood stasis, and its mechanism may be related to inhibiting the activation of TLR4/NF-κB signaling pathway and regulating the balance of inflammatory cytokine network.

knee osteoarthritis  /  icariin  /  kidney deficiency and blood stasis  /  inflammatory response  /  TLR4/NF-κB signaling pathway