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Scopolin isolated from Erycibe obtusifolia Benth stems suppresses adjuvant-induced rat arthritis by inhibiting inflammation and angiogenesis

scopolinrheumatoidarthritisangiogenesisinflammationvegf

摘要:Objective To study the effects and mechanisms of scopolin isolated from the stems of Erycibe obtusifolia Benth in arthritis-associated inflammation and angiogenesis.Methods Adjuvant-induced arthritic rat,an animal model for human RA was used in this study for examining the potential remedial effect of scopolin.The swelling in both inoculated and non-inoculated paws,body weights and articular index(AI)scores were detected to evaluate the severity of the arthritis.Histologic assessment of tissue sections from rat ankles was also performed.Furthermore,the blood vessel density in the synovial tissues was quantitatively evaluated.In addition,expressions of VEGF,FGF-2,TNF-α,IL-1β and IL-6 in rat synovial tissues were determined by immunohistochemistry assay in an attempt to explain the mechanisms of scopolin for suppressing arthritis.Results Scopolin dose-dependently inhibited both inoculated and non-inoculated paw swelling in rat AIA.The mean AI scores of scopolin treated groups were also dose-dependently lower than that of model group.In addition,compared with the weights of model group,the mean body weights of rats treated with scopolin(50,100 mg·kg-1)were higher from day 13 to 22,perhaps indicative of healthier animals.The histologic architecture of the joint was highly abnormal in the model group rats,while high dose of scopolin treated rats preserved a nearly normal histologic architecture of the joint.Moreover,the new blood vessels were reduced dose-dependently in the synovial tissue of rat AIA treated with scopolin.Further,scopolin reduced the overexpression of IL-6,VEGF and FGF-2 in rat synovial tissues.Conclusions Scopolin is capable of reducing clinical symptoms of rat AIA by inhibiting inflammation and angiogenesis,and this compound may be a potent therapeutic agent for angiogenesis related diseases and can serve as structural base for screening for more potent synthetic analogs.

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