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

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.

Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-κB signaling pathway in weaned piglets with intrauterine growth retardation

“…(2019) demonstrated that DHA derivative (9α, 12α-dihydroartemisinyl) bis (2′-chlorocinnmate) (DC32) inhibited inflammatory response in osteoarthritic synovium of rats via regulating Nrf2/NF-κB pathway. The study of Liu et al. (2017) also showed that dihydroartemisinin alleviated autoimmune thyroiditis of rats by inhibiting the CXCR3/PI3K/AKT/NF-κB signaling pathway.…”

Dihydroartemisinin ameliorates psoriatic skin inflammation and its relapse by diminishing CD8+ T-cell memory in wild-type and humanized mice

“…Thus, developing new drugs for treating psoriasis are always needed to prevent its recurrence. DHA, a derivative of artemisinin, has been demonstrated to have immunosuppressive effects on some inflammatory diseases, such as encephalomyelitis, thyroiditis and lupus nephritis, in experimental animal models 32 , 34 , 37 although it remains unknown whether DHA exerts an effect on these diseases in clinic. Moreover, DHA can regulate the differentiation and apoptosis of T cells 23 , 32 .…”

Dihydroartemisinin Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma Partially by Targeting AKT1 and p70S6K

“…DHA treatment inhibits the phosphorylation of AKT and induces glioma cells apoptosis ( Du et al, 2015 ; Shao et al, 2017 ). In the autoimmune thyroiditis (AIT), DHA inhibits the CXCR3/PI3K/AKT/NF-κB signaling pathway which executes important roles in AIT ( Liu et al, 2017 ). DHA and gefitinib co-administration also downregulate the levels of phosphorylated p-AKT and p-mTOR to inhibit the proliferation and migration of non-small cell lung cancer cells ( Jin et al, 2017 ).…”