在自身免疫和炎症性疾病领域，干扰素基因环化 GMP-AMP 合酶 (cGAS) 刺激剂 (STING) 信号通路已被彻底研究和建立。尽管如此，针对 cGAS-STING 通路的药物的临床批准仍然有限。白芍总苷（TGP）具有很强的抗炎作用，常用于治疗类风湿性关节炎（RA），这是我们研究的一个主题。我们发现，在小鼠骨髓源性巨噬细胞 (BMDM) 和东北医院儿科 - 1 (THP-1) 细胞中，TGP 显着降低了由各种 cGAS-STING 激动剂触发的 cGAS-STING 信号通路的激活。这种抑制作用与干扰素调节因子 3 (IRF3) 磷酸化和干扰素-β (IFN-β)、C-X-C 基序趋化因子配体 10 (CXCL10) 和炎症介质如肿瘤坏死因子-α (TNF) 的表达抑制一起被发现。 -α) 和白介素-6 (IL-6)。作用机制似乎涉及 TGP 减弱 STING-IRF3 相互作用，而不影响 STING 寡聚化，从而抑制下游信号通路的激活。在体内，TGP 阻碍了 STING 激动剂二甲基呫吨酮-4-乙酸 (DMXAA) 启动 cGAS-STING 通路，并在脂多糖 (LPS) 和 D-半乳糖胺诱导的急性肝损伤模型中表现出良好的治疗效果。 D-GalN）。我们的研究结果强调了 TGP 作为 cGAS-STING 通路有效抑制剂的潜力，为该通路介导的炎症和自身免疫性疾病提供了新的治疗途径。版权所有 © 2024 中国药科大学。由 Elsevier B.V. 出版。保留所有权利。

In the realm of autoimmune and inflammatory diseases, the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway has been thoroughly investigated and established. Despite this, the clinical approval of drugs targeting the cGAS-STING pathway has been limited. The Total glucosides of paeony (TGP) is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis (RA), emerged as a subject of our study. We found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway, triggered by various cGAS-STING agonists, in mouse bone marrow-derived macrophages (BMDMs) and Tohoku Hospital Pediatrics-1 (THP-1) cells. This inhibition was noted alongside the suppression of interferon regulatory factor 3 (IRF3) phosphorylation and the expression of interferon-beta (IFN-β), C-X-C motif chemokine ligand 10 (CXCL10), and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mechanism of action appeared to involve the TGP's attenuation of the STING-IRF3 interaction, without affecting STING oligomerization, thereby inhibiting the activation of downstream signaling pathways. In vivo, the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid (DMXAA) and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN). Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway, offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.