1.School of Pharmacy，Anhui University of Chinese Medicine，Hefei 230012，China;2.Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China
Objective To explore the intervention effect of Yuxuebi tablet （YXB） on collagen-induced arthritis （CIA） in rats and its anti-inflammatory mechanism.Method Following CIA modeling， the rats in the drug administration groups were separately treated with intragastric administration of YXB （0.1， 0.2， and 0.4 g·kg-1） and methotrexate （MTX， 0.4 mg·kg-1）， once a day. The incidence of CIA， mechanical pain threshold （MPT） and cold pain threshold （CPT） were evaluated once every three days. After continuous administration for 30 days， the peripheral blood of rats was collected for the determination of platelet （PLT） count and fibrinogen （FIB） content. The hematoxylin-eosin （HE） staining was conducted to analyze the pathological changes in joint tissues. The protein expression levels of interleukin （IL）-1β， IL-8， nuclear transcription factor-κB （NF-κB） p65， phosphorylated NF-κB （p-NF-κB） p65， Ras， and Raf-1 in joint tissues of CIA rats were detected by immunohistochemistry （IHC） and Western blot. The rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were induced by tumor necrosis factor-α （TNF-α， 10 μg·L-1） in vitro and then subjected to transwell migration/invasion assay， followed by the detection of protein expression levels of Ras， Raf-1， and p-NF-κB p65 in RA-FLS by Western blot.Result Compared with the control group， the model group exhibited an increased incidence of CIA， significantly decreased MPT （P<0.05，P<0.01）， elevated CPT （P<0.01） and PLT and FIB in the peripheral blood， worsened histopathological score of joints， enhanced RA-FLS migration and invasion， and up-regulated inflammatory factors （P<0.01）. The comparison with the model group revealed that YXB at different doses obviously reduced the incidence of CIA， increased MPT， down-regulated CPT and PLT and FIB in the peripheral blood （P<0.05，P<0.01）， ameliorated the pathological changes like synovial hyperplasia and bone and cartilage destruction （P<0.05，P<0.01）， and inhibited RA-FLS migration and invasion. Besides， the low-， medium-， and high-dose YXB reversed the IL-1β， IL-8， Ras， Raf-1， and p-NF-κB p65 expression in joint tissues of CIA rats to different extents， as well as the protein expression of Ras， Raf-1 and p-NF-κB p65 in RA-FLS （P<0.05，P<0.01）.Conclusion YXB reduces the incidence of CIA， ameliorates the clinical symptoms of RA and the pathological changes in joint tissues， and inhibits the formation of synovium， which may be attributed to its inhibition against Ras/Raf-1/NF-κB signaling pathway.
® 2021 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.