Artemisinin-Related Therapeutic Strategies for Autoimmune Thyroiditis: Chemokine–Receptor Networks, Spatial Thyroid Biology, and Molecular Mechanisms

Yuanyuan Sun,1 Xuelian Yang,2 Qimo Zhu,3 Rong Yang4 1Department of Endocrinology, The People’s Hospital of Liaoning Province, Shenyang, 110016, People’s Republic of China; 2Material Management Department, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China; 3The Second Clinical College, China Medical University, Shenyang, 110004, People’s Republic of China; 4Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Rong Yang, Department of Endocrinology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, 110004, People’s Republic of China, Tel +86-24-24016709, Email [email protected]: Autoimmune thyroiditis (AIT) is a chronic immune-mediated thyroid disorder characterized by lymphocytic infiltration, follicular epithelial injury, autoantibody production, and variable progression to thyroid dysfunction. Because current management is largely supportive or replacement based, there is growing interest in interventions that might modify inflammatory and immune processes before irreversible tissue damage develops. This narrative review critically evaluates the potential, but not yet established, role of Artemisia-derived and artemisinin-related compounds in AIT. The analysis focuses on chemokine–receptor networks, spatial organization of thyroid inflammation, and molecular mechanisms linking endoperoxide/redox chemistry, innate immune signaling, and immune-cell trafficking. Evidence was identified through targeted, non-systematic searches of PubMed and Google Scholar, supported by backward and forward citation tracking. Thyroid-specific evidence remains limited and predominantly preclinical. Dihydroartemisinin (DHA) has been reported to attenuate experimental autoimmune thyroiditis by reducing inflammatory infiltration, thyroid autoantibodies, Th1/Th17-associated responses, CXCL10/CXCR3-linked signaling, and oxidative stress. Evidence from non-thyroid autoimmune and inflammatory models suggests additional effects on NF-κB, MAPK, PI3K/Akt/mTOR, JAK/STAT, TLR/MyD88, NRF2/GPX4-related redox responses, inflammasome activity, regulatory T-cell balance, and possible epigenetic remodeling; however, these findings should be treated as mechanistic context rather than direct evidence for human AIT. Most available studies involve purified or semi-synthetic compounds rather than standardized botanical preparations, and robust clinical validation is absent. Artemisinin-related compounds are therefore framed as hypothesis-driven immunomodulatory candidates that require thyroid-specific replication, target validation, comparative pharmacology, safety assessment, formulation standardization, and carefully designed translational studies before clinical application can be considered. The infographic details artemisinin-related chemotypes in autoimmune thyroiditis (AIT). 1. Disease-Relevant Pathways Potentially Modulated: NF-kB and MAPK (Inflammation), PI3K/Akt/mTOR (Cell survival), JAK/STAT (Cytokine signaling), TLR/MyD88 (Innate immunity), NRF2/Redox (Oxidative balance). Modulation may vary. 2. Reported Mainly for DHA in EAT models: Inflammatory infiltration, Autoantibodies, Th1/Th17 responses, CXCL10/CXCR3-linked signaling, Oxidative stress. 3. Key Limitations: Standardization of botanical preparations, Compound authentication, Dose-response validation, Safety/toxicity, Lack of robust human AIT trials. 4. Candidate Chemotypes (Evidence Strength): D (Direct preclinical EAT evidence: Dihydroartemisinin), S (Supportive: Amino-artemisinins), H (Hypothesis-generating: Synthetic ozonides). 5. Cautious Translational Pathway: Target validation, Early translational studies, Clinical development if justified. All candidate compounds remain investigational.Artemisinin chemotypes in thyroiditis: pathways, limits and translation.Keywords: autoimmune thyroiditis, artemisinin derivatives, chemokine–receptor networks, spatial thyroid biology, innate immune signaling