Network Pharmacology Studies on the Molecular Mechanism of Hashimoto's Thyroiditis Treated with Shutiao Qiji Decoction
Authors: Guo Shuang , Lv Yan , Shen Junyu , Li Rong , Liu Haipeng , Fan Yuan , Tian Chunhong 
Published: November 2023

Background:
In recent years, the number of patients with Hashimoto's thyroiditis has
been increasing, and traditional Chinese medicine ingredients and combinations have been applied
to treat Hashimoto's thyroiditis to increase efficacy and reduce side effects during the
treatment process.

Objective:
Shutiao Qiji Decoction is one of the Chinese traditional medicine prescriptions, which
is commonly used to treat cancer, tumor, etc. It is also used for thyroid-related diseases in the
clinic. Hashimoto’s thyroiditis is an autoimmune disease. In this study, the mechanism of
Shutiao Qiji Decoction in treating Hashimoto's thyroiditis was studied through network pharmacology
and molecular docking verification.

Method:
Each Chinese medicine ingredient of Shutiao Qiji Decoction was retrieved from the Traditional
Chinese Medicine Systems Pharmacology (TCMSP) database. The related genes of HT were
searched from the UniProt and GeneCards databases. Meanwhile, we used Cytoscape to construct
the protein-protein interaction (PPI) visual network analysis, and used the search tool to search the
database of Interacting Genes (STRING) to build a PPI network. These key proteins were enriched
and analyzed by molecular docking validation, Gene Ontology (GO), and the Kyoto Encyclopedia
of Genes and Genomes (KEGG). Hashimoto's thyroiditis disease model was established in SD rats,
and SQD was administered by gavage after the successful establishment of the model. After 6
weeks of continuous administration of the drug by gavage, tissue samples were collected and the
thyroid and spleen tissues were visualized by HE staining to verify the therapeutic effect.

Results:
The results showed that there were 287 TCM active ingredients, 1920 HT-related disease
targets, and 176 drug and disease targets in SQD. Through PPI analysis, GP analysis, and
KEGG analysis of the common targets of drugs and diseases, we found their pathways of action
to be mainly cancer action pathway, PI3K-AKT signaling pathway, and T-cell action pathway.
The active ingredients of the drugs in SQD, malvidin, stigmasterol, porin-5-en-3bta-ol, and chrysanthemum
stigmasterol, were docked with the related target proteins, MAPK, GSK3β, TSHR,
and NOTCH molecules. The best binding energies obtained from docking were mairin with
TSHR, stigmasterol with TSHR, poriferast-5-en-3beta-ol with MAPK, and chryseriol with
GSK3β, with binding energies of -6.84 kcal/mol, -6.53 kcal/mol, -5.03 kcal/mol, and -5.05
kcal/mol, respectively. HE staining sections of rat thyroid and spleen tissues showed that SQD
had a therapeutic effect on Hashimoto's thyroiditis and restored its immune function.

Conclusion:
It is verified by molecular docking results that Shutiao Qiji Decoction has a potential
therapeutic effect on Hashimoto's thyroiditis in the MAPK/TSHR/NOTCH signal pathway,
and that the main components, mairin, stigmasterol, poriferast-5-en-3beta-ol, and chryseriol play
a role in it. SQD has been shown to have a good therapeutic effect on Hashimoto's thyroiditis.