Network Pharmacology Studies on the Molecular Mechanism of Hashimoto's Thyroiditis Treated with Shutiao Qiji Decoction


Citar

Texto integral

Resumo

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.

Sobre autores

Shuang Guo

College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine

Autor responsável pela correspondência
Email: info@benthamscience.net

Yan Lv

College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine

Email: info@benthamscience.net

Junyu Shen

College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Rong Li

College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine

Email: info@benthamscience.net

Haipeng Liu

The Second Affiliated Hospital, Yunnan University of Traditional Chinese Medicine

Email: info@benthamscience.net

Yuan Fan

College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine,

Email: info@benthamscience.net

Chunhong Tian

, Yunnan Research Institute of Traditional Chinese Medicine

Email: info@benthamscience.net

Bibliografia

  1. Jin, B.; Wang, S.; Fan, Z. Pathogenesis markers of hashimoto’s disease-a mini review. Frontiers in Bioscience-Landmark, 2022, 27(10), 297. doi: 10.31083/j.fbl2710297 PMID: 36336870
  2. Mincer, D.L.; Jialal, I. Hashimoto Thyroiditis. In: In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2022.
  3. Weetman, A.P. An update on the pathogenesis of Hashimoto’s thyroiditis. J. Endocrinol. Invest., 2021, 44(5), 883-890. doi: 10.1007/s40618-020-01477-1 PMID: 33332019
  4. Ragusa, F.; Fallahi, P.; Elia, G. Hashimotos’ thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract. Res. Clin. Endocrinol. Metab., 2019, 33(6), 101367. doi: 10.1016/j.beem.2019.101367 PMID: 31812326
  5. Li, X.; Li, X.; Huang, N.; Liu, R.; Sun, R. A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins. Phytomedicine, 2018, 50, 73-87. doi: 10.1016/j.phymed.2018.09.174 PMID: 30466994
  6. Lu, J.; Li, W.; Gao, T.; Wang, S.; Fu, C.; Wang, S. The association study of chemical compositions and their pharmacological effects of Cyperi Rhizoma (Xiangfu), a potential traditional Chinese medicine for treating depression. J. Ethnopharmacol., 2022, 287, 114962. doi: 10.1016/j.jep.2021.114962 PMID: 34968659
  7. Ao, M.; Li, X.; Liao, Y. Curcumae Radix: A review of its botany, traditional uses, phytochemistry, pharmacology and toxicology. J. Pharm. Pharmacol., 2022, 74(6), 779-792. doi: 10.1093/jpp/rgab126 PMID: 34633034
  8. Ma, J.; Chen, X.; Bian, Y.Q. Study on efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma for promoting blood circulation and remving blood stasis based on systematic traditional Chinese medicine Zhongguo Zhong Yao Za Zhi, 2020, 45(14), 3259-3265. doi: 10.19540/j.cnki.cjcmm.20200210.404
  9. Zheng, Y.Q.; Zeng, J.X.; Lin, J.X. Herbal textual research on chuanxiong rhizoma in Chinese classical prescriptions. Zhongguo Zhong Yao Za Zhi, 2021, 46(16), 4293-4299. doi: 10.19540/j.cnki.cjcmm.20210523.104
  10. Liu, L.; Wang, Y.; Tan, C.; Han, X.; Dou, D. Substance basis of warm nature of Poria cocos. Chin. Herb. Med., 2020, 12(3), 316-325. doi: 10.1016/j.chmed.2020.04.002 PMID: 36119008
  11. Zhu, B.; Zhang, Q.; Hua, J.; Cheng, W.; Qin, L. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: A review. J. Ethnopharmacol., 2018, 226, 143-167. doi: 10.1016/j.jep.2018.08.023 PMID: 30130541
  12. Li, P.; Tsang, M.S.M.; Kan, L.L.Y. The immuno-modulatory activities of pentaherbs formula on ovalbumin-induced allergic rhinitis mice via the activation of th1 and treg cells and inhibition of Th2 and Th17 cells. Molecules, 2021, 27(1), 239. doi: 10.3390/molecules27010239 PMID: 35011470
  13. Chen, S.Y.; Zhou, Q.Y.J.; Chen, L.; Liao, X.; Li, R.; Xie, T. The Aurantii Fructus Immaturus flavonoid extract alleviates inflammation and modulate gut microbiota in DSS-induced colitis mice. Front. Nutr., 2022, 9, 1013899. doi: 10.3389/fnut.2022.1013899 PMID: 36276817
  14. Gao, Y.; Shi, W.; Tu, C. Immunostimulatory activity and structure-activity relationship of epimedin B from Epimedium brevicornu Maxim. Front. Pharmacol., 2022, 13, 1015846. doi: 10.3389/fphar.2022.1015846 PMID: 36386137
  15. Ding, Y.; Brand, E.; Wang, W.; Zhao, Z. Licorice: Resources, applications in ancient and modern times. J. Ethnopharmacol., 2022, 298, 115594. doi: 10.1016/j.jep.2022.115594 PMID: 35934191
  16. Xu, J.X.; Xu, J.; Cao, Y. Modern research progress of traditional Chinese medicine Paeoniae Radix Alba and prediction of its Q-markers. Zhongguo Zhong Yao Za Zhi, 2021, 46(21), 5486-5495. doi: 10.19540/j.cnki.cjcmm.20210818.201
  17. Zhang, D.; Zhang, Y.; Zhang, C. Discussion on the treatment of depression in traditional Chinese medicine with Zhang Zhenshu Tiaoqi Decoction, a Chinese medical master. Yunnan J Tradit Chin Med, 2021, 42(12), 12-14. doi: 10.16254/j.cnki.53-1120/r.2021.12.005
  18. Pu, W. The experience of Zhang Zhen, a Chinese medical master, in treating infertility based on the theory of regulating qi. Yunnan J Tradit Chin Med, 2022, 43(9), 4-7. doi: 10.16254/j.cnki.53-1120/r.2022.09.002
  19. Nogales, C.; Mamdouh, Z.M.; List, M.; Kiel, C.; Casas, A.I.; Schmidt, H.H.H.W. Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends Pharmacol. Sci., 2022, 43(2), 136-150. doi: 10.1016/j.tips.2021.11.004 PMID: 34895945
  20. Wang, Z.Y.; Wang, X.; Zhang, D.Y. Traditional Chinese medicine network pharmacology: Development in new era under guidance of network pharmacology evaluation method guidance. Zhongguo Zhong Yao Za Zhi, 2022, 47(1), 7-17. doi: 10.19540/j.cnki.cjcmm.20210914.702
  21. Jiashuo, W.U.; Fangqing, Z.; Zhuangzhuang, L.I.; Weiyi, J.; Yue, S. Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review. J. Tradit. Chin. Med., 2022, 42(3), 479-486. J. doi: 10.19852/j.cnki.jtcm.20220408.003 PMID: 35610020
  22. Kahaly, G.J.; Diana, T.; Olivo, P.D. TSH receptor antibodies: Relevance & utility. Endocr. Pract., 2020, 26(1), 97-106. doi: 10.4158/EP-2019-0363 PMID: 32022598
  23. Zhou, Y.; Shen, H.; Lan, W.; Shi, Y.; Yao, Q.; Wen, W. Mechanism of Xiaoying Daotan decoction in treating Hashimoto’s thyroiditis based on the Notch/Treg/Th17 pathway. Ann. Transl. Med., 2021, 9(24), 1760. doi: 10.21037/atm-21-6253 PMID: 35071454
  24. Hu, X.; Chen, Y.; Shen, Y.; Tian, R.; Sheng, Y.; Que, H. Global prevalence and epidemiological trends of Hashimoto’s thyroiditis in adults: A systematic review and meta-analysis. Front. Public Health, 2022, 10, 1020709. doi: 10.3389/fpubh.2022.1020709 PMID: 36311599
  25. Martinez Quintero, B.; Yazbeck, C.; Sweeney, L.B. Thyroiditis: Evaluation and treatment. Am. Fam. Physician, 2021, 104(6), 609-617. PMID: 34913664
  26. Du, P.; Xu, J.; Jiang, Y. Saikosaponin-d attenuates hashimoto’s thyroiditis by regulating macrophage polarization. J. Immunol. Res., 2022, 2022, 1-12. doi: 10.1155/2022/7455494 PMID: 36398316
  27. Zhu, G.; Li, Y.; Gao, Y. Treatment of malignant tumors based on the theory of "one body, two wings, and qi regulating mechanism. J. Tradit. Chin. Med., 2020, 35(10), 5046-5049.
  28. Hordyjewska, A.; Prendecka-Wróbel, M.; Kurach, Ł. Antiproliferative properties of triterpenoids by ECIS method—a new promising approach in anticancer studies? Molecules, 2022, 27(10), 3150. doi: 10.3390/molecules27103150 PMID: 35630627
  29. Bakrim, S.; Benkhaira, N.; Bourais, I. Health benefits and pharmacological properties of stigmasterol. Antioxidants, 2022, 11(10), 1912. doi: 10.3390/antiox11101912 PMID: 36290632
  30. Zhang, R.T.; Wu, H.N.; Yu, G.H. Effective components and signaling pathways of Epimedium brevicornumbased on network pharmacology. Zhongguo Zhong Yao Za Zhi, 2018, 43(23), 4709-4717. doi: 10.19540/j.cnki.cjcmm.20180905.001
  31. Aboulaghras, S.; Sahib, N.; Bakrim, S. Health benefits and pharmacological aspects of chrysoeriol. Pharmaceuticals, 2022, 15(8), 973. doi: 10.3390/ph15080973 PMID: 36015121
  32. Xinyi, L.I. Treatment of Hashimoto’s thyroiditis from spleen theory. Jiangsu Tradit Chin Med, 2023, 55(07), 49-52. doi: 10.19844/j.cnki.1672-397X.2023.07.014

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Bentham Science Publishers, 2024