Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 1; p. 18
• Main Authors: Chen, Jian-Yu, Yang, Ying-Jie, Ma, Xue-Qin, Cao, Qi, Wei, Shan-Shan, Pan, Rong-Rong, Nan, Li-Hong, Liu, Yao-Jun, Cao, Yan, Tian, Xiao-Yun, Deng, Shan, Cheng, Zai-Xing, Wang, Can-Jian, Chen, Tao, Zheng, Yan-Fang, Huang, Ming-Qing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.12.2022; MDPI
• Subjects: activators of transcription 3 (STAT3); Antagonism; Apoptosis; Autoimmune diseases; Autoimmune Diseases - metabolism; Cell cycle; Cell Differentiation; Cell growth; Cell viability; Cytokines; Differentiation (biology); Drug dosages; Flavonoids; Helper cells; Herbal medicine; Humans; Immune system; Immunofluorescence; Immunoregulation; Inactivation; Inflammation; Inflammatory bowel disease; Inflammatory diseases; Interleukin 17; Lymphocytes; Lymphocytes T; neobaicalein (NEO); Pathogenesis; Pharmacology; Phosphorylation; signal transducer; Signal Transduction; Splenocytes; Stat3 protein; STAT3 Transcription Factor - metabolism; Stat4 protein; Stat5 protein; STAT5 Transcription Factor - metabolism; Stat6 protein; T cells; T-Lymphocytes, Regulatory; Th17; Th17 Cells; Transcription factors; Tumor necrosis factor-α; China; autoimmune diseases; activators of transcription 3 (STAT3); neobaicalein (NEO); signal transducer; Th17
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28010018

Huangqin is the dried root of 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.