Sun Peng, Zhu Lili, Yu Yang, Hu Sijing, Shan Mengyi, Zhao Xuan, Wang Xinchang, Zhang Qiaoyan, Qin Luping
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China.
Department of Rheumatology, the Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310000, China.
Chin J Nat Med. 2025 Jun;23(6):733-741. doi: 10.1016/S1875-5364(25)60892-2.
Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently 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-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d·20 g. 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 nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine 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 indicated 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 submandibular 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 cytokine 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 responses through the PI3K/AKT and JAK1/STAT3 pathways.
干燥综合征（SS）是一种主要以口腔和眼周干燥为特征的自身免疫性疾病。黄芪 - 丹参（AS）和麦冬 - 石斛（OD）是SS治疗中常用的两味药对。虽然AS - OD药对组合在缓解SS症状方面显示出临床疗效，但其潜在机制仍不清楚。本研究旨在评估AS - OD对患有SS的非肥胖糖尿病（NOD）/Ltj小鼠的治疗效果，并阐明其潜在机制。该研究使用NOD/Ltj小鼠作为SS模型，以113.1、226.2和339.3 mg·d·20 g的剂量给予AS - OD治疗10周。结果表明，AS - OD改善了SS症状，表现为NOD/Ltj小鼠唾液流速增加、抗SSA/Ro和抗SSB/La抗体水平降低、游泳持续时间延长以及乳酸（LA）和血尿素氮（BUN）水平降低。AS - OD减少了淋巴细胞浸润，增强了下颌下腺中水通道蛋白5（AQP5）的表达，降低了下颌下腺中炎性细胞因子水平，并降低了脾脏中辅助性T细胞17/调节性T淋巴细胞（Th17/Treg）细胞比例。转录组学和蛋白质组学分析表明，AS - OD参与调节磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/AKT）和Janus激酶3/信号转导和转录激活因子3（JAK1/STAT3）通路，在NOD/Ltj小鼠下颌下腺和A - 253细胞中均验证了其抑制作用。此外，AS - OD通过PI3K/AKT通路增强细胞活力并减少A - 253细胞凋亡。在A - 253细胞中，AS - OD通过抑制JAK1/STAT3通路降低炎性细胞因子水平、CXC趋化因子配体9/10（CXCL9/10）以及T细胞趋化性。AS - OD通过PI3K/AKT和JAK1/STAT3通路抑制炎症和免疫反应来减轻SS。
