Dihydroartemisinin attenuates autoimmune thyroiditis by inhibiting the CXCR3/PI3K/AKT/NF-κB signaling pathway

// Huijuan Liu 1, 2, * , Qin Tian 1, * , Xiaoyu Ai 1, * , Yuan Qin 1 , Zhanhong Cui 1 , Meng Li 1 , Jiahuan Yang 1 , Denghui Zhai 1 , Yanrong Liu 3 , Shuang Chen 3 , Jing Meng 1 , Tao Sun 1, 3 , Honggang Zhou 1, 3 and Cheng Yang 1, 3 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, College of Life Sciences, Nankai University, Tianjin, China 2 College of Life Sciences, Nankai University, Tianjin, China 3 Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China * These authors have contributed equally to this work Correspondence to: Cheng Yang, email: cyang66_2001@yahoo.com Honggang Zhou, email: honggang.zhou@vip.126.com Tao Sun, email: sunrockmia@hotmial.com Keywords: DHA; AIT; CXCR3; PI3K; NF-κB Received: September 19, 2017     Accepted: November 13, 2017     Published: December 01, 2017 ABSTRACT Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT in vitro and in vivo . Results showed that DHA can visibly reduce antithyroglobulin antibody and thyroid peroxidase antibody levels and regulate T helper cells (Th) 1/Th2 imbalance of experimental AIT mice. DHA also dose-dependently suppressed proliferation of lymphocytes induced by lipopolysaccharide and concanavalin A. DHA inhibited binding of C-X-C chemokine ligand 10 (CXCL10) and its receptor (C–X–C motif) receptor 3 (CXCR3), thus inhibiting calcium flow. DHA can also reduce expression levels of PI3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, nuclear factor (NF)-κB/p65, and p-NF-κB/p65. In conclusion, DHA may serve as treatment drug for AIT by inhibiting the CXCR3/PI3K/AKT/NF-kB signaling pathway.