Therapeutic Effect Of Troxerutin On Adjuvant-induced Arthritis And Its Mechanisms In Rats

AIM: To observe the therapeutic effect of troxerutin on adjuvant-indced arthritic rats and to investigate its possible mechanisms.METHODS: Furend's complete adjuvant (FCA) was used to induce adjuvant arthritis in rats. The experimental rats were administered with troxerutin (18, 36, 72 mg·kg-1) by ig for 8 days after treatment with FCA for 2 weeks. Aspirin (30 mg·kg-1) was also given as positive control. Secondary paw swelling of adjuvant arthritic rats was measured with volume meter. Polyarthritis index was calculated by five grade scoring method. Histopathological change of joint was observed by light microscope. Hemorheology indexes, including whole blood viscosity (WBV), plasma viscosity (PV), serum viscosity (SV), hematocrit (HCT), fibrinogen and erythrocyte aggregation index, were measured by blood viscometer. Rat joint synoviocytes were cultured in vitro. The levels of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) in supernatants were measured by radioimmunoassay method, respectively.RESULTS: Compared with normal rats, the rat joints in model group were swelling distinctly, and arthritic index was also increasing markedly. Under light microscope, the synovial tissue in inflammatory joints was thickening and showed 3~5 layer synoviocytes, and part of synoviocytes showed villous proliferation. In joint periphery tissue, hyperemia, edema and infiltration of inflammatory cells were seen. Articular cartilage tissue was destructed accompanied with collagen fibre hyperplasia and pannus formation. Hemorheology of arthritic rats was also abnormal markedly, the WBV, PV and SV were increased under different shear rate, and the erythrocyte aggregation index and fibrinogen content were also increased significantly. In vitro, levels of PGE2, IL-1 and TNF-αin cultured synoviocyte supernatants were elevated distinctly.After treatment with troxerutin 36, 72 mg·kg-1 for 8 days (d14-d21), the paw swelling and polyarthritis index of adjuvant arthritic rats were diminished obviously, the synovial hyperplasia was inhibited, the hemorheology index was improved significantly and showed dose-dependent manner. The experimental results demonstrated that troxerutin (36, 72 mg·kg-1) significantly reduced the elevation of PGE2, IL-1 and TNF-αin cultured synoviocyte supernatants. Correlation analysis showed that the effect of troxerutin reducing joint swelling was closely related to its inhibitory effects of PGE2, IL-1 and TNF-αproduction by synoviocytes, and their correlation coefficients were 0.9567, 0.9432 and 0.9258, respectively.CONCLUSIONS: Troxerutin has definite treatment effect for adjuvant-induced arthritis, one of its therapeutic mechanisms might be associated with improving abnormal hemorheology, and inhibition of troxerutin on PGE2, IL-1 and TNF-αproduction by synoviocytes might be an important therapeutic mechanism.