Abstract: Objective: To investigate the preventive effect and mechanisms of glucosamine (GLU) combined with drynariae rhizome (DR) on osteoarthritis (OA) of rats. Methods: A rat model of chronic arthritis was established by injection of kaolin and carrageen-λ into the articular cavity to induce acute osteoarticular injury combined with run, which was preceded by intragastric administration of GLU (750 mg/kg), DR (150 mg/kg), low-, medium- and high-dose GLU + DR (125 mg/kg GLU + 25 mg/kg DR, 250 mg/kg GLU + 50 mg/kg DR, and 750 mg/kg GLU + 150 mg/kg DR), diclofenac sodium (DS, 2 mg/kg, positive control), and sterile distilled water (10 mL/kg, for control and model groups) until the end of a 6 week run on a threadmill. Arthroncus in rats was measured. Tissue sections of knee joints were prepared by paraffin embedding and staining with hematoxylin eosin and saffron-O-solid green to observe the pathological changes of articular cartilage. The levels of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum were detected with enzyme-linked immunosorbent assay (ELISA) kits. Superoxide dismutase (SOD) activity and nitric oxide (NO) content in serum were measured by xanthine oxidase and nitrate reductase methods, respectively. The expression of type Ⅱ collagen was detected by immunohistochemistry. Results: Compared with the control group, arthroncus in rats in the model group was increased and the cartilage was destroyed. Moreover, MMP-3 and TIMP-1 concentrations and MMP-3/TIMP-1 ratio were significantly increased as well as iNOS activity and of IL-1β, NO and TNF-α concentrations(P < 0.05), while SOD activity and type Ⅱ collagen expression were significantly declined (P < 0.05). Compared with the model group, GLU and DR alone as well as their combination at medium and high doses could reduce arthroncus, improve pathological abnormality in knee joint tissue, significantly inhibit the increase in MMP-3, TIMP-1, IL-1β, NO and TNF-α contents and iNOS activity, and significantly suppress the decrease in SOD activity and type II collagen content (P < 0.05), and the best effect was observed with highdose GLU + DR followed by GLU, DR, and GLU + DR at medium and low doses. Conclusion: Separate and combined GLU and RD can attenuate osteoarticular injury, but an effective dose is required for the combined treatment. The potential mechanism of action may be related to the regulation of MMP-3/TIMP-1 balance, resulting in increased SOD activity and type Ⅱ collagen content as well as decreased iNOS activity and IL-1β, TNF-α and NO contents. This study can provide a theoretical basis for the development of functional foods for the prevention and treatment of OA.

Key words: glucosamine, drynaria rhizome, osteoarthritis, articular cartilage