Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation
Jian-Yu Chen,
Ying-Jie Yang,
Xue-Qin Ma,
Qi Cao,
Shan-Shan Wei,
Rong-Rong Pan,
Li-Hong Nan,
Yao-Jun Liu,
Yan Cao,
Xiao-Yun Tian,
Shan Deng,
Zai-Xing Cheng,
Can-Jian Wang,
Tao Chen,
Yan-Fang Zheng,
Ming-Qing Huang
Affiliations
Jian-Yu Chen
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Ying-Jie Yang
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Xue-Qin Ma
Key Laboratory of Hui Ethnic Medicine Modernization, Department of Pharmaceutical Analysis, School of Pharmacy, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China
Qi Cao
School of Pharmacy, Second Military Medical University, No. 325, Guo He Road, Shanghai 200433, China
Shan-Shan Wei
School of Pharmacy, Second Military Medical University, No. 325, Guo He Road, Shanghai 200433, China
Rong-Rong Pan
Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, No. 358, Datong Road, Pudong New Area, Shanghai 200137, China
Li-Hong Nan
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Yao-Jun Liu
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Yan Cao
School of Pharmacy, Second Military Medical University, No. 325, Guo He Road, Shanghai 200433, China
Xiao-Yun Tian
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Shan Deng
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Zai-Xing Cheng
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Can-Jian Wang
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Tao Chen
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Yan-Fang Zheng
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
Ming-Qing Huang
Department of Pharmacology, School of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1, Hua Tuo Road, Min Hou Shang Jie, Fuzhou 350122, China
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.
