1.Study on mechanism of the effective substance groups from Artemisia ordosica in ameliorating rheumatoid arthritis
HUGEJILE ; Qinghu WANG ; Xiaofeng ZHANG ; Xiurong KANG ; Yingchun BAI ; LIHURICHA ; Mingxia GAO
China Pharmacy 2025;36(13):1604-1609
OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica(Abbreviated as HSH)on rheumatoid arthritis(RA)based on cluster of differentiation 4/lymphocyte cell-specific protein-tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17(CD4/LCK/ZAP70/IL-17)signaling pathway.METHODS The rats were divided into normal group,model group,HSH low-dose,medium-dose and high-dose groups(2.7,10.8,21.6 mg/kg)and positive control group(Tripterygium glycosides tablet,6.3 mg/kg),with 10 rats in each group.Except for normal group,RA rat model was induced by complete Freund's adjuvant in other groups.After modeling,each group was given relevant medicine or normal saline intragastrically,once a day,for 28 consecutive days.The changes in ankle joint swelling and arthritis index in rats were determined;the pathological changes of ankle joint tissue were observed;the levels of inflammatory factors[IL-1β,IL-21,IL-17A,IL-2,interferon-γ(IFN-γ)and IL-6]in serum and joint fluid of rats were determined;the levels of Th1,Th17 and Treg cells in the whole blood and spleen of rats were detected;protein and mRNA expressions of LCK,proto-oncogene tyrosine-protein kinase Fyn(Fyn),ZAP70,CD45,RAR-related orphan receptor γt(RORγt),and forkhead box protein 3(Foxp3)in ankle synovial tissue were determined.RESULTS Compared with normal group,the changes in ankle joint swelling,arthritis index,the levels of IL-1β,IL-21,IL-17A,IL-2,IFN-γ and IL-6 in serum and joint fluid,the levels of Th1,Th17 cells and Th17/Treg value in whole blood and spleen,and the protein and mRNA expression levels of LCK,Fyn,ZAP70,CD45,and RORγt in ankle joint synovium were all significantly increased/elevated(P<0.05).The level of Treg cells in the spleen,as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased(P<0.05).Compared with model group,most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH(P<0.05).The degree of pathological changes in ankle joint tissues was markedly improved,and inflammation was alleviated.CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway,thereby modulating the Th17/Treg balance.This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA.

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