Combination of Astragalus-Salvia and Ophiopogon-Dendrobium herb pairs alleviates Sj?gren's Syndrome via inhibiting the JAK1/STAT3 and PI3K/AKT pathways in NOD/Ltj mice
摘要Sj?gren's syndrome(SS)is an autoimmune disease characterized primarily by oral and peri-ocular dryness.Astragalus-Salvia(AS)and Ophiopogon-Dendrobium(OD)represent two fre-quently utilized herb pairs in SS treatment.While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms,its underlying mechanism remains unclear.This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic(NOD)/Ltj mice with SS.The study utilized NOD/Ltj mice as SS models,administering AS-0D treatment for 10 weeks at doses of 113.1,226.2,and 339.3 mg·d-1·20 g-1.Results demonstrated that AS-OD improved SS symptoms,evidenced by enhanced salivary flow rate,decreased anti-SSA/Ro and anti-SSB/La antibody levels,increased swimming duration,and reduced lactate(LA)and blood urea nitro-gen(BUN)levels in NOD/Ltj mice.AS-OD reduced lymphocyte infiltration,enhanced Aquaporin-5(AQP5)expression in the submandibular gland,decreased inflammatory cy-tokine levels in the submandibular gland,and reduced the T helper type 17/regulatory T lymphocyte(Th17/Treg)cell ratio in the spleen.Transcriptomic and proteomic analyses in-dicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)and Janus kinase 3/signal transducer and activator of transcription 3(JAK1/STAT3)pathways,with inhibitory effects validated in both NOD/Ltj mice submandibu-lar gland and A-253 cells.Furthermore,AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway.In A-253 cells,AS-OD reduced inflammatory cy-tokine levels,CXC chemokine ligand 9/10(CXCL9/10),and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway.AS-OD mitigates SS by suppressing inflammation and immune re-sponses through the PI3K/AKT and JAK1/STAT3 pathways.
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