Therapeutic Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate on Collagen-Induced Arthritis in Rats

Objective:To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate(DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis(CIA).Methods:Wistar rat model of CIA was set up using bovine collagen type Ⅱ.Fifty rats were divided into five groups randomly:normal,CIA model,DDB treatment,methotrexate(MTX) treatment,and combined DDB+MTX treatment.Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints.Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining.Plasma levels of vascular endothelial growth factor(VEGF),platelet derived growth factor,interleukin-8(IL-8),IL-4,tumor necrosis factor α(TNF-α),and cyclooxygenase-2(COX-2) were quantified by enzyme-linked immunosorbent assay.Nitric oxide levels were detected by Griess reagent.Results:Compared with the CIA model group,a remarkable reduction in various angiogenic(VEGF and IL-8) and inflammatory mediators(TNF-α,IL-4 and COX-2) after treatment with DDB either alone or combined with MTX(P<0.05 or P<0.01).Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect.The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.Conclusion:Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis(RA) compared with a choice drug(MTX) and it may be offered as a second-line drug in the treatment of RA.