紫丁香苷是一种苯丙素糖苷，具有多种生物学特性，包括对各种免疫和炎症性疾病的抑制活性。在这项研究中，评估了从卷叶青牛胆中分离的丁香苷下调活化核因子-κB (NF-κB)、磷酸肌醇-3-激酶-Akt (PI3K-Akt) 和丝裂原激活蛋白激酶 (MAPK) 的能力。 ) 脂多糖激活 U937 巨噬细胞中的信号转导网络。丁香苷对前列腺素 E2 (PGE2)、环氧合酶-2 (COX-2)、白介素-1β (IL-1β) 和肿瘤坏死因子-α 产生的减弱作用(TNF-α)，并通过 ELISA、Western blot 和 qRT-PCR 检测信号通路中信号分子的表达。紫丁香苷通过显着减少 PGE2 的产生，下调 NF-κB、MAPKs 和 PI3K-Akt 信号网络通过抑制 COX-2 基因和蛋白质表达水平在巨噬细胞中发挥作用。它还减少 TNF-α 和 IL-1β 的分泌及其 mRNA 表达，抑制 NF-κB (p65)、IKKα/β 和 IκBα 的磷酸化，并恢复 IκBα 的降解能力。丁香苷剂量依赖性减弱 Akt、p38 MAPK、JNK 和 ERK 磷酸化。此外，相应上游信号分子 Toll 样受体 4 (TLR4) 和骨髓分化初级反应基因 88 (MyD88) 的表达在紫丁香苷治疗后下调。紫丁香苷对 MyD88 中炎症信号分子的抑制作用依赖性途径表明它有潜力作为候选药物，开发成治疗各种免疫介导的炎症性疾病的药物。© 2024。作者获得 Springer Nature B.V. 的独家许可。

Syringin, a phenylpropanoid glycoside, has exhibited numerous biological properties including inhibitory activities against various immune and inflammatory disorders. In this study, syringin isolated from Tinospora crispa was evaluated for its ability to down-regulate activated nuclear factor-kappa B (NF-κB), phosphoinositide-3-kinase-Akt (PI3K-Akt) and mitogen-activated protein kinases (MAPKs) signal transducing networks in U937 macrophages activated by lipopolysaccharide.The attenuating effects of syringin on the productions of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and the expressions of signaling molecules of the signaling pathways were investigated by using ELISA, Western blot, and qRT-PCR.Syringin downregulated the NF-κB, MAPKs, and PI3K-Akt signal networks by significantly reducing PGE2 production in the macrophages via suppression of COX-2 gene and protein expression levels. It also reduced TNF-α and IL-1β secretion and their mRNA expression, suppressed phosphorylation of NF-κB (p65), IKKα/β, and IκBα, and restored ability of IκBα to degrade. Syringin dose-dependently attenuated Akt, p38 MAPKs, JNK, and ERK phosphorylation. Also, the expression of corresponding upstream signaling molecules toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) were down-regulated in response to syringin treatment.The suppressive effect of syringin on the inflammatory signaling molecules in MyD88-dependent pathways suggested it's potential as a drug candidate for development into an agent for treatment of various immune-mediated inflammatory disorders.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.