Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps
OBJECTIVE To explore the improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis(RA)rats by regulating neutrophil extracellular traps(NETs).METHODS Establishment of rat RA model using bovine type Ⅱ collagen and Freund's complete adjuvant.The model rats were randomly divided into model group and low-dose,middle-dose and high-dose groups(55,110,220 mg/kg)of petroleum ether extract of S.divaricata;the normal group without modeling was also established,with 10 rats in each group.Each group was given corresponding drugs or constant volume of 2%Tween-80 solution intragastrically,once a day,for consecutive 28 days.The toe swelling degree in rats was observed,and the arthritis index(AI)was scored.The serum levels of interleukin-1β(IL-1β),IL-10,IL-17,tumor necrosis factor-α(TNF-α),25-hydroxyvitamin D3[25(OH)D3],myeloperoxidase(MPO),neutrophil elastase(NE)and NETs in rats were detected.The histopathological changes in ankle joint were observed.The expression of citrullinated histone H3(CitH3)in ankle joint as well as the expressions of cytochrome P450 24A1(CYP24A1),cytochrome P450 27B1(CYP27B1),vitamin D receptor(VDR)and peptidyl arginine deiminase 4(PAD4)in synovium were all determined.RESULTS Compared with the model group,the toe swelling degree and AI score in the middle-dose and high-dose groups of petroleum ether extract of S.divaricata decreased significantly from day 14 to day 28 after administration(P＜0.05 or P＜0.01).The serum levels of IL-1β,IL-17,TNF-α,MPO,NE and NETs decreased significantly,while the levels of IL-10 and 25(OH)D3 increased significantly(P＜0.05 or P＜0.01).The widened ankle joint space and the improved structure were found;the expression of CitH3 in ankle joint,and the expressions of CYP24A1 and PAD4 in synovium were down-regulated significantly,while the expressions of CYP27B1 and VDR were up-regulated significantly in synovium(P＜0.05 or P＜0.01).CONCLUSIONS The petroleum ether extract of S.divaricata may inhibit the production of NETs and improve the symptoms of RA by regulating the vitamin D system.
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