title: Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling.
abstract: Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Zimu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gu
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Da
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular, Dalian Medical University, Dalian, 116044, China. yingkong@dmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China. rongxinz@yahoo.com.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D005260:Female; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000473:pathology; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D005663:Furans; D017705:Lignans; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D047495:PPAR gamma; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; C071942:arctigenin
keywords: AMPK; Arctigenin; Experimental autoimmune encephalomyelitis; PPAR-γ; Th17 cells