Dihydroartemisinin inhibits the development of autoimmune thyroiditis by modulating oxidative stress and immune imbalance

Abstract

Autoimmune thyroiditis is among the most prevalent autoimmune endocrine illnesses. However, the pathophysiology has not been determined, and efficacious treatments are still lacking. The current study used network pharmacology analysis and an experimental autoimmune thyroiditis (EAT) mouse model to explore whether dihydroartemisinin (DHA) has therapeutic effects on autoimmune thyroiditis and to investigate the potentially related mechanisms concerning oxidative stress (OS) responses and T-cell immune imbalance. The therapeutic effects of DHA on autoimmune thyroiditis and potentially related processes were first anticipated using network pharmacology analysis and then verified using the EAT model. DHA may influence the onset of autoimmune thyroiditis by regulating immune imbalance and OS responses, according to network pharmacology analysis. ELISA, immunofluorescence staining, and histopathological examination were used to detect changes in serum thyroid autoantibody levels and intrathyroidal inflammatory infiltration following DHA intervention. RT-PCR was used to determine the spleen's mRNA expression of typical T-cell cytokines, whereas an OS kit and immunohistochemical staining were used to assess the thyroid's glutathione (GSH) content, superoxide dismutase (SOD) activity, and Nrf2 protein expression. Furthermore, serum TgAb levels and intrathyroidal inflammatory infiltrates were considerably lower in EAT mice given high-dose DHA than in vehicle-treated controls. In the spleen, IFN-γ, IL-17A, and IL-6 mRNA expressions were dramatically downregulated, while IL-4 and IL-10 were significantly raised. Following high-dose DHA treatment, GSH content, SOD activity, and Nrf2 protein expression levels were markedly increased in thyroid tissue. These findings imply that DHA administration may suppress TgAb formation and reduce intrathyroidal inflammatory cell infiltration by restoring T-cell immune imbalance and increasing antioxidant capacity via the Nrf2 pathway. This study provides important experimental data for DHA's therapeutic use in patients with autoimmune thyroiditis.