Abstract: BACKGROUND: Yanghe Decoction is an effective prescription for the clinical treatment of knee osteoarthritis. Our previous basic studies have shown that the mechanism of Yanghe Decoction to prevent and treat knee osteoarthritis is related to the protection of articular cartilage. It is still not unclear about the effect of Yanghe Decoction on early synovial inflammation of knee osteoarthritis. 
OBJECTIVE: To investigate the effect of Yanghe Decoction on the pain and synovial inflammation in a rabbit model of early knee osteoarthritis, and to further clarify the efficacy and mechanism of Yanghe Decoction in the treatment of early osteoarthritis.
METHODS: Twenty-four 4-month-old New Zealand rabbits were randomly divided into blank control group, model group, Yanghe Decoction group and positive control group, with six rabbits in each group. Except for the blank control group, the rabbits in the other groups were injected with papain into the joint cavity for modeling. Two weeks after modeling, the blank control and model groups were given the same amount of normal saline by gavage, the Yanghe Decoction group was given 6 g/kg/d Yanghe Decoction, and the positive control group was given 24 mg/kg/d Celebrex. Administration in each group lasted for 2 weeks. At 4 hours after final administration, the knee joint skin temperature and circumference were measured, and Lequesne MG score was used to evaluate knee joint function. At 2 days after final intragastric administration, ELISA was used to detect the levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2 in the synovial fluid. Synovial tissue morphology was observed using hematoxylin-eosin staining. Immunohistochemical detection was conducted to detect the expression of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 proteins in synovial tissue. 
RESULTS AND CONCLUSION: Compared with the blank control group, the knee joint circumference in the model group was widened (P < 0.05), and the local skin temperature, Lequesne MG score, and the levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2 in the synovial fluid were all increased (P < 0.05), synovial membrane morphology and inflammatory changes were obvious, and the expressions of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 proteins in synovial tissue were all increased (P < 0.05). Compared with the model group, the knee joint circumference in the Yanghe Decoction group and positive control group decreased (P < 0.05), local skin temperature, Lequesne MG score, and the levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2 in the synovial fluid were all decreased (P < 0.05), synovial membrane morphology and inflammatory changes were alleviated, and the expressions of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 proteins in synovial tissue were all downregulated (P < 0.05). In conclusion, Yanghe Decoction can inhibit the expression of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2, reduce synovial inflammation, and improve joint function, thereby delaying the progression of knee osteoarthritis.

Key words: Yanghe Decoction, early knee osteoarthritis, synovium, pain, inflammation, mechanism of action, New Zealand rabbit