Combination of Astragalus-Salvia and Ophiopogon-Dendrobium herb pairs alleviates Sjögren’s Syndrome via inhibiting the JAK1/STAT3 and PI3K/AKT pathways in NOD/Ltj mice

Sjögren's syndrome (SS) is an autoimmune disease with primary clinical manifestations of oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) are the two most common herb pairs for SS treatment. Combination of AS-OD herb pairs is clinically effective in relieving SS, but the underlying action mechanism remains elusive. This study aimed to evaluate the alleviating effect and explore the potential mechanisms of AS-OD on SS in NOD/Ltj mice. NOD/Ltj mice were employed as SS models and subjected to a 10-week treatment with AS-OD at dose of 113.1 mg·d⁻¹·20 g⁻¹, 226.2 mg·d⁻¹·20 g⁻¹, and 339.3 mg·d⁻¹·20 g⁻¹. The result showed that AS-OD improved the symptoms of SS as evidenced by the increased salivary flow rate, reduced levels of anti-SSA/Ro antibody and anti-SSB/La antibody, enhanced swimming duration, and decreased LA and BUN levels in NOD/Ltj mice. AS-OD attenuated lymphocyte infiltration and increased the expression of AQP5 submandibular gland and reduced level of inflammatory cytokines in the submandibular gland and decreased the ratio of Th17/Treg cells in the spleen. Transcriptomic and proteomic analyses suggest that AS-OD may be involved in the regulation of PI3K/AKT and JAK1/STAT3 pathways, and AS-OD has an inhibitory effect on PI3K/AKT and JAK1/STAT3 pathways, which were validated in the submandibular gland of NOD/LTJ mice and A-253 cells. Additionally, AS-OD increased cell viability, suppressed A-253 cells apoptosis via the PI3K/AKT pathway. AS-OD decreased levels of inflammatory cytokines, CXCL9/10 and T-cell chemotaxis by inhibiting JAK1/STAT3 pathway in A-253 cells. AS-OD alleviates SS by reducing inflammation and immune responses via the PI3K/AKT and JAK1/STAT3 pathways.