Abstract: BACKGROUND: Astragalus polysaccharide has a certain role in the treatment of arthritis, and abnormal Toll-like receptor 4/nuclear factor κB pathway plays an important role in the pathogenesis of knee osteoarthritis. 
OBJECTIVE: To investigate the effect of astragalus polysaccharide on osteoarthritis and its mechanism. 
METHODS: Forty SD rats were randomly divided into control group (the same volume of normal saline), model group (the same volume of normal saline), astragalus polysaccharide low-dose group (0.2 mL of 0.1 /L astragalus polysaccharide intervention), astragalus polysaccharide high-dose group (0.2 mL of 0.5 g/L astragalus polysaccharide intervention), and lipopolysaccharide group (0.2 mL of 0.5 g/L astragalus polysaccharide+0.2 mL of 500 µg/kg lipopolysaccharide). Interventions in each group began at 1 week after modeling, once every 3 days, for 6 continuous weeks. After intervention, histopathological changes of the cartilage and synovial membrane were observed by hematoxylin-eosin staining and saffron O-solid green staining. Mankin’s score and Osteoarthritis Research Society International score were performed for histological evaluation. The levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, nitric oxide, malondialdehyde, and superoxide dismutase in synovial tissue were detected by ELISA. The protein levels of Aggrecan, collagen type II, matrix metalloproteinase 3, nuclear factor-κB p65, Toll-like receptors 4 and myeloid differentiation factor 88 in cartilage tissue were detected by western blot assay. 
RESULTS AND CONCLUSION: (1) Compared with the model group, the Mankin’s score, Osteoarthritis Research Society International score, the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, nitric oxide, malondialdehyde, and matrix metalloproteinase 3, and the expressions of nuclear factor-κB p65, Toll-like receptors 4, and myeloid differentiation factor 88 were significantly decreased in the astragalus polysaccharide low- and high-dose groups, while the expression levels of Aggrecan, collagen type II, and superoxide dismutase activity were significantly increased (P < 0.05). Furthermore, the astragalus polysaccharide high-dose group showed better effects than the low-dose group (P < 0.05). (2) Compared with the astragalus polysaccharide high-dose group, the Mankin’s score, Osteoarthritis Research Society International score, the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, nitric oxide, malondialdehyde, matrix metalloproteinase 3 and the expressions of nuclear factor-κB p65, Toll-like receptors 4, and myeloid differentiation factor 88 were significantly increased in the lipopolysaccharide group, while the superoxide dismutase activity and the expressions of Aggrecan and collagen type II were significantly decreased (P < 0.05). (3) To conclude, astragalus polysaccharide can improve extracellular matrix degradation, inflammatory response, and oxidative stress levels, and alleviate joint injury due to knee osteoarthritis by inhibiting the activation of Toll-like receptor 4/nuclear factor κB p65 pathway. 

Key words: astragalus polysaccharides, knee osteoarthritis, inflammation, Toll-like receptor 4, nuclear factor κB p65, rat