Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation.
Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation.
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新黄芩素通过阻断 STAT3 信号传导抑制 Th17 细胞分化，从而恢复 Th17/Treg 比率
DOI：
10.3390/molecules28010018
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发表时间：
2022-12-20
期刊：
影响因子：
--
通讯作者：
Huang MQ
中科院分区：
文献类型：
--
作者：
Chen JY;Yang YJ;Ma XQ;Cao Q;Wei SS;Pan RR;Nan LH;Liu YJ;Cao Y;Tian XY;Deng S;Cheng ZX;Wang CJ;Chen T;Zheng YF;Huang MQ
黄芩为黄芩的干燥根，在中医概念中被广泛用于清热去湿、泻火、解毒，在临床方剂中用于治疗炎症和癌症。新黄芩素 (NEO) 是从黄芩中分离出来的黄酮类化合物，已发表的研究报道称其具有显着的抗炎作用。 Th17/Treg平衡向Th17细胞转移是自身免疫性炎症性疾病发生的重要原因。然而，NEO在Th17和Treg中的作用及其潜在机制尚未阐明。基于网络药理学的研究表明，NEO 主要调节 IL-17 信号通路。此外，我们的结果表明，NEO (3–30 μmol/L) 以浓度依赖性方式下调 Th17 分化、细胞上清液和细胞内 IL-17A 水平以及肿瘤坏死因子 α 的产生。进一步的机制研究表明，NEO还特异性抑制脾细胞中STAT3（Tyr725）和STAT4（Y693）的磷酸化，而不影响STAT5和STAT6的激活。免疫荧光结果表明NEO有效阻断STAT3转入细胞核。有趣的是，适当剂量的 NEO 只能抑制 Th17 细胞分化，对 Treg 分化没有影响。本研究表明，NEO 通过特异性阻断 STAT3 信号传导的激活而不失活 STAT5 和 STAT6，有效抑制 Th17 细胞分化。 NEO 对 STAT4 激活的额外抑制作用也表明其对抗 Th1 分化的潜力。所有工作都表明，NEO 可能是通过抑制免疫细胞活力和 T 细胞分化来进行免疫调节和治疗自身免疫炎症性疾病的潜在候选者。
Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3–30 μmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation.
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