Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling

Drug Des Devel Ther. 2023 Aug 2:17:2273-2285. doi: 10.2147/DDDT.S410901. eCollection 2023.

Abstract

Background: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear.

Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively.

Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group.

Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.

Keywords: TLR4/NF-κB; autoimmune thyroiditis; dioscin; transcriptome.

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Hashimoto Disease*
  • NF-kappa B
  • Rats
  • TOR Serine-Threonine Kinases
  • Thyroglobulin / adverse effects
  • Thyroiditis, Autoimmune* / chemically induced
  • Thyroiditis, Autoimmune* / drug therapy
  • Thyrotropin / blood
  • Thyroxine / blood
  • Toll-Like Receptor 4
  • Triiodothyronine / blood

Substances

  • Autoantibodies
  • dioscin
  • mTOR protein, rat
  • NF-kappa B
  • Thyroglobulin
  • Thyrotropin
  • Thyroxine
  • Toll-Like Receptor 4
  • TOR Serine-Threonine Kinases
  • Triiodothyronine

Grants and funding

This work was supported by the Key Laboratory of TCM Health Cultivation of Beijing (grant number BZ0259) and the international science and technology cooperation projects (grant number 2015DFA30910).