Total glucosides of paeony alleviates Sjogren syndrome through inhibiting inflammatory responses in mice

OBJECTIVE To study the therapeutic effects of TGP on SS both in C57BL/6J mice immunized by immu⁃nological induction(SS mice)and NOD/ShiltJNju(NOD)mice.METHODS TGP(180,360,720 mg·kg^-1)was intragastri⁃cally administered for 6 or 16 weeks for SS mice and NOD mice,respectively.Weekly food and water intake,saliva flow,submandibular gland(SMG)and spleen index,and SMG pathology were measured.ELISA was used to evaluate serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and autoantigens(SSA/Ro,SSB/La,andα-fodrin).Real-time PCR and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA TNF-α,IL-17A,CXCL9,CXCL13,and B-cell activating factor(BAFF)and protein(IL-1β,IL-6,TNF-α,and IFN-γ)expres⁃sion.RESULTS Compared with SS mice,TGP(720 mg·kg^-1)treatment increased saliva flow,reduced organ indexes,and decreased serum IL-6 and IFN-γ concentration.TGP(360 mg·kg^-1)treatment decreased serum IFN-γ concentra⁃tion.TGP(180,360,720 mg·kg^-1)treatment improved SMG pathological damage.Compared with NOD mice,the saliva flowincreased from 9 to 15 weeks of administration.After 2 weeks of administration,TGP(720 mg·kg^-1)treatment decreased serum SSA/Ro,SSB/La and a-fodrin concentration,increased SMG index,inhibited SMG IFN-γ concentra⁃tion,and down-regulated SMG TNF-α,IL-17A,CXCL9,CXCL13 and BAFF mRNA expression.TGP(360 mg·kg^-1)treat⁃ment decreased serum SSB/La and a-fodrin,and SMG TNF-α and IFN-γ concentration,and down-regulated SMG TNF-α,IL-17A,CXCL9 and BAFF mRNA expression.TGP(180 mg·kg^-1)treatment decreased serum SSB/La,a-fodrin,and SMG IL-1β concentration,and down-regulated SMG TNF-α,IL-17A and BAFF mRNA expression.After 8 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment increased SMG index,and decreased serum a-fodrin concentra⁃tion.TGP(720 mg·kg^-1)treatment down-regulated mRNA expression of SMG TNF-α,IL-17A,CXCL9,CXCL13,and BAFF.TGP(360 mg·kg^-1)treatment reduced mRNA expression of TNF-α,CXCL9,CXCL13 and BAFF,and concentra⁃tion of IL-6 and TNF-α.TGP(180 mg·kg^-1)treatment down-regulated mRNA expression of TNF-α,CXCL9,and CXCL13,and decreased IL-6 and TNF-αconcentration in SMG.After 16 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment reduced serum SSA/Ro and a-fodrin concentration,increased SMG index,and decreased SMG CXCL13 and BAFF mRNA expression.TGP(360,720 mg·kg^-1)treatment decreased serum SSB/Laconcentration and SMG TNF-α,IL-17A and CXCL9 mRNA expression.Besides,TGP(180,360,720 mg·kg^-1)treatment alleviated the pathological damage of SMG after 2 and 16 weeks of administration.CONCLUSION TGP has a certain therapeutic effect onmice through inhibiting inflammatory responses.