夏枯草治疗甲状腺结节的作用机制潜在药理机制
Potential Pharmacological Mechanism of Action Mechanism of Spica prunellae in Treating Thyroid Nodule
DOI: 10.12677/ACM.2023.131156, PDF,  被引量   
作者: 刘 洋, 赵蕙琛, 张玉超, 左 丹:青岛大学附属青岛市市立医院,山东 青岛;柴家超*:青岛市妇女儿童医院,山东 青岛;刘元涛:山东大学齐鲁医院(青岛),山东 青岛
关键词: 网络药理学分子对接夏枯草甲状腺结节Network Pharmacology Molecular Docking Spica prunellae Thyroid Nodule
摘要: 目的:确定夏枯草(Spica prunellae, SP)治疗甲状腺结节(thyroid nodule, TN)的有效性和潜在机制。方法:首先,从公开数据库搜集夏枯草活性成分对应靶点及甲状腺结节的靶点。通过网络拓扑分析、GO和KEGG通路富集分析筛选关键靶点和机制。应用分子对接来验证夏枯草与靶点的关系。结果:夏枯草试验组在治疗甲状腺结节可提高临床总有效率,经网络分析,6个靶点(AKT1、TP53、IL6、MAPK3、MAPK1、CASP3)被识别为关键治疗靶点。富集分析表明,潜在机制集中在与炎症、增殖和凋亡相关的生物过程和途径。关键途径被认为是PI3K-AKT信号通路。结论:本研究阐明SP可能通过PI3K-AKT途径抑制炎症和增殖并促进细胞凋亡,是一种潜在的治疗甲状腺结节的药物。
Abstract: Objective: This research is to identify the underlying and efficient mechanism of Spica prunellae (SP) in the treatment of thyroid nodule (TN). Methods: Firstly, the targets corresponding to the ac-tive components of Prunella vulgaris and the targets of thyroid nodules were collected from public databases. The key targets and mechanisms were screened by network topology analysis, GO and KEGG pathway enrichment analysis. Molecular docking was used to verify the relationship between Prunella vulgaris and target. Results: Meta-analysis revealed that Prunella vulgaris significantly improved the total clinical effective rate in the treatment of thyroid nodules, network pharmacology suggested that 6 targets (AKT1, TP53, IL6, MAPK3, MAPK1, CASP3) were identified as dominating therapeutic targets after network analysis. The results of enrichment analysis suggested that the potential mechanism was concentrated mainly on the biological processes and pathways associated with inflammation, proliferation, and apoptosis. Especially, the main pathway was regarded as the PI3K-AKT signaling pathway. Conclusion: SP may suppress tumor, inflammation and proliferation and promote apoptosis through the PI3K-AKT pathway, which makes SP a potential treatment against TN.
文章引用:刘洋, 柴家超, 赵蕙琛, 刘元涛, 张玉超, 左丹. 夏枯草治疗甲状腺结节的作用机制潜在药理机制[J]. 临床医学进展, 2023, 13(1): 1128-1138. https://doi.org/10.12677/ACM.2023.131156

参考文献

[1] Wong, R., Farrell, S.G. and Grossmann, M. (2018) Thyroid Nodules: Diagnosis and Management. Medical Journal of Australia, 209, 92-98. [Google Scholar] [CrossRef] [PubMed]
[2] Durante, C., Grani, G., Lamartina, L., et al. (2018) The Diagnosis and Management of Thyroid Nodules: A Review. JAMA, 319, 914-924. [Google Scholar] [CrossRef] [PubMed]
[3] 郭巧生, 陈宇航. 夏枯草基原植物及其食疗历史考证[J]. 中国中药杂志, 2011, 36(21): 3057-3062.
[4] Hwang, Y.-J., Lee, E.-J., Kim, H.-R. and Hwang, K.-A. (2013) NF-κB-Targeted Anti-Inflammatory Activity of Prunella vulgaris var. lilacina in Macrophages RAW 264.7. Internation-al Journal of Molecular Sciences, 14, 21489-21503. [Google Scholar] [CrossRef] [PubMed]
[5] Tan, J., Qi, H. and Ni, J. (2015) Extracts of Endophytic Fungus xkc-s03 from Prunella vulgaris L. spica Inhibit Gastric Cancer in Vitro and in Vivo. Oncology Letters, 9, 945-949. [Google Scholar] [CrossRef] [PubMed]
[6] Kim, H.-I., Quan, F.-S., Kim, J.-E., et al. (2014) Inhibition of Estrogen Signaling through Depletion of Estrogen Receptor Alpha by Ursolic Acid and Betulinic Acid from Prunella vulgaris var. lilacina. Biochemical and Biophysical Research Communications, 451, 282-287. [Google Scholar] [CrossRef] [PubMed]
[7] 竺夏静, 范尧夫, 张会峰, 等. 夏枯草口服液治疗甲状腺功能亢进症的系统评价[J]. 药物评价研究, 2021, 44(8): 1764-1771.
[8] 李明, 王晓佳, 刘刚. 夏枯草口服液联合左甲状腺素钠治疗结节性甲状腺肿患者的效果[J]. 中国民康医学, 2021, 33(16): 68-70.
[9] 战群. 基于数据挖掘技术探析中药治疗亚急性甲状腺炎的用药规律[D]: [硕士学位论文]. 长春: 长春中医药大学, 2019: 1-53.
[10] 朱晨垚. 基于数据挖掘分析张兰教授治疗甲状腺结节的经验及用药规律[D]: [硕士学位论文]. 沈阳: 辽宁中医药大学, 2021: 1-47.
[11] Hopkins, A.L. (2008) Network Pharmacology: The Next Paradigm in Drug Discovery. Nature Chem-ical Biology, 4, 682-690. [Google Scholar] [CrossRef] [PubMed]
[12] Aguayo-Orozco, A., Audouze, K., Brunak, S. and Taboureau, O. (2016) In Silico Systems Pharmacology to Assess Drug’s Therapeutic and Toxic Effects. Current Pharmaceutical Design, 22, 6895-6902. [Google Scholar] [CrossRef] [PubMed]
[13] Ru, J., Li, P., Wang, J., et al. (2014) TCMSP: A Da-tabase of Systems Pharmacology for Drug Discovery from Herbal Medicines. Journal of Cheminformatics, 6, Article No. 13. [Google Scholar] [CrossRef] [PubMed]
[14] Liu, H., Wang, J., Zhou, W., Wang, Y. and Yang, L. (2013) Sys-tems Approaches and Polypharmacology for Drug Discovery from Herbal Medicines: An Example Using Licorice. Journal of Ethnopharmacology, 146, 773-793. [Google Scholar] [CrossRef] [PubMed]
[15] Varma, M.V., Obach, R.S., Rotter, C., et al. (2010) Physicochemical Space for Optimum Oral Bioavailability: Contribution of Human Intestinal Absorption and First-Pass Elimination. Jour-nal of Medicinal Chemistry, 53, 1098-1108. [Google Scholar] [CrossRef] [PubMed]
[16] Tao, W., Xu, X., Wang, X., et al. (2013) Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Radix Curcumae Formula for Application to Cardiovascular Disease. Journal of Ethnopharmacology, 145, 1-10. [Google Scholar] [CrossRef] [PubMed]
[17] Yang, H., Zhang, W., Huang, C., et al. (2014) A Novel Systems Pharmacology Model for Herbal Medicine Injection: A Case Using Reduning Injection. BMC Complementary and Al-ternative Medicine, 14, Article No. 430. [Google Scholar] [CrossRef] [PubMed]
[18] Zhang, Y., Li, X., Guo, C., Dong, J. and Liao, L. (2020) Mecha-nisms of Spica prunellae against Thyroid-Associated Ophthalmopathy Based on Network Pharmacology and Molecular Docking. BMC Complementary Medicine and Therapies, 20, Article No. 229. [Google Scholar] [CrossRef] [PubMed]
[19] Kim, S., Chen, J., Cheng, T., et al. (2019) PubChem 2019 Up-date: Improved Access to Chemical Data. Nucleic Acids Research, 47, D1102-D1109. [Google Scholar] [CrossRef] [PubMed]
[20] Gfeller, D., Grosdidier, A., Wirth, M., et al. (2014) SwissTargetPredic-tion: A Web Server for Target Prediction of Bioactive Small Molecules. Nucleic Acids Research, 42, W32-W38. [Google Scholar] [CrossRef] [PubMed]
[21] Boyadjiev, S. and Jabs, E. (2000) Online Mendelian Inheritance in Man (OMIM) as a Knowledgebase for Human Developmental Disorders. Clinical Genetics, 57, 253-266. [Google Scholar] [CrossRef] [PubMed]
[22] Piñero, J., Bravo, À., Queralt-Rosinach, N., et al. (2017) DisGeNET: A Comprehensive Platform Integrating Information on Human Disease-Associated Genes and Variants. Nu-cleic Acids Research, 45, D833-D839. [Google Scholar] [CrossRef] [PubMed]
[23] Rebhan, M., Chalifa-Caspi, V., Prilusky, J. and Lancet, D. (1998) Gene-Cards: A Novel Functional Genomics Compendium with Automated Data Mining and Query Reformulation Support. Bi-oinformatics, 14, 656-664. [Google Scholar] [CrossRef] [PubMed]
[24] Szklarczyk, D., Morris, J.H., Cook, H., et al. (2017) The STRING Database in 2017: Quality-Controlled Protein-Protein Association Networks, Made Broadly Accessible. Nu-cleic Acids Research, 45, D362-D368. [Google Scholar] [CrossRef] [PubMed]
[25] Huang, D.W., Sherman, B.T. and Lempicki, R.A. (2008) Systematic and Integrative Analysis of Large Gene Lists Using DAVID Bioinformatics Resources. Nature Protocols, 4, 44-57. [Google Scholar] [CrossRef] [PubMed]
[26] Shannon, P., et al. (2003) Cytoscape: A Software Environment for In-tegrated Models of Biomolecular Interaction Networks. Genome Research, 13, 2498-2504. [Google Scholar] [CrossRef] [PubMed]
[27] Missiuro, P.V., Liu, K., Zou, L., et al. (2009) Information Flow Analysis of Interactome Networks. PLOS Computational Biology, 5, e1000350. [Google Scholar] [CrossRef] [PubMed]
[28] 庄莉, 翟园园, 姚卫峰, 等. 基于网络药理学的二至丸对肾脏保护作用的机制研究[J]. 药学学报, 2019, 54(5): 877-885.
[29] Belviranli, M., Okudan, N. and Lamprecht, M. (2015) Well-Known Antioxidants and Newcomers in Sport Nutrition: Coenzyme Q10, Quercetin, Resveratrol, Pterostil-bene, Pycnogenol and Astaxanthin. In: Lamprecht, M., Ed., Antioxidants in Sport Nutrition, Chapter 5, CRC Press/Taylor & Francis, Boca Raton.
[30] Zhang, N., Liu, S., Shi, S., et al. (2020) Solubilization and Delivery of Ur-solic-Acid for Modulating Tumor Microenvironment and Regulatory T Cell Activities in Cancer Immunotherapy. Journal of Controlled Release, 320, 168-178. [Google Scholar] [CrossRef] [PubMed]
[31] Lim, D.Y., Jeong, Y., Tyner, A.L. and Park, J.H.Y. (2007) In-duction of Cell Cycle Arrest and Apoptosis in HT-29 Human Colon Cancer Cells by the Dietary Compound Luteolin. American Journal of Physiology-Gastrointestinal and Liver Physiology, 292, G66-G75. [Google Scholar] [CrossRef] [PubMed]
[32] Ou, H.-C., Pandey, S., Hung, M.Y., et al. (2019) Luteolin: A Natu-ral Flavonoid Enhances the Survival of HUVECs against Oxidative Stress by Modulating AMPK/PKC Pathway. The American Journal of Chinese Medicine, 47, 541-557. [Google Scholar] [CrossRef
[33] Jia, Z., Chen, A., Wang, C., et al. (2019) Amelioration Effects of Kaempferol on Immune Response Following Chronic Intermittent Cold-Stress. Research in Veterinary Science, 125, 390-396. [Google Scholar] [CrossRef] [PubMed]
[34] Mo, J.-S., Choi, D., Han, Y.-R., Kim, N. and Jeong, H.-S. (2019) Morin Has Protective Potential against ER Stress Induced Apoptosis in Renal Proximal Tubular HK-2 Cells. Bi-omedicine & Pharmacotherapy, 112, Article ID: 108659. [Google Scholar] [CrossRef] [PubMed]
[35] Sun, H.-X., Qin, F. and Pan, Y.-J. (2005) In Vitro and in Vivo Immunosuppressive Activity of Spica prunellae Ethanol Extract on the Immune Responses in Mice. Journal of Eth-nopharmacology, 101, 31-36. [Google Scholar] [CrossRef] [PubMed]
[36] 侯东升, 张静, 冯丽, 等. 熊果酸对甲状腺癌TPC-1细胞增殖的抑制作用[J]. 医学研究生学报, 2020, 33(7): 720-725.
[37] Wang, X., Li, M., Hu, M., Wei, P. and Zhu, W. (2017) BAMBI Overexpression Together with β-Sitosterol Ameliorates NSCLC via Inhibiting Autophagy and Inactivating TGF-β/Smad2/3 Pathway. Oncology Reports, 37, 3046-3054. [Google Scholar] [CrossRef] [PubMed]
[38] Quagliariello, V., Armenia, E., Aurilio, C., et al. (2016) New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded with Quer-cetin Alone or in Combination to an Inhibitor of Aurora Kinase. Journal of Cellular Physiology, 231, 1784-1795. [Google Scholar] [CrossRef] [PubMed]
[39] Gül, N, Üzüm, A.K., Selçukbiricik, Ö.S., et al. (2018) Prevalence of Papil-lary Thyroid Cancer in Subacute Thyroiditis Patients May Be Higher than It Is Presumed: Retrospective Analysis of 137 Patients. Radiology and Oncology, 2, 257-262. [Google Scholar] [CrossRef] [PubMed]
[40] Chen, Y.-K., Lin, C.-L., Chang, Y.-J., et al. (2013) Cancer Risk in Patients with Graves’ Disease: A Nationwide Cohort Study. Thyroid, 23, 879-884. [Google Scholar] [CrossRef] [PubMed]
[41] Chen, Y.-K., Lin, C.-L., Chang, F.T.-F., Sung, F.-C. and Kao, C.-H. (2013) Cancer Risk in Patients with Hashimoto’s Thyroiditis: A Nationwide Cohort Study. British Journal of Cancer, 109, 2496-2501. [Google Scholar] [CrossRef] [PubMed]
[42] Chang, H., Shin, B.K., Kim, A., Kim, H.K. and Kim, B.H. (2016) DNA Methylation Analysis for the Diagnosis of Thyroid Nodules—A Pilot Study with Reference to BRAFV600E Mutation and Cytopathology Results. Cytopathology, 27, 122-130. [Google Scholar] [CrossRef] [PubMed]
[43] Ruggeri, R.M., Villari, D., Simone, A., et al. (2012) Co-Expression of Interleukin-6 (IL-6) and Interleukin-6 Receptor (IL-6R) in Thyroid Nod-ules Is Associated with Co-Expression of CD30 Ligand/CD30 Receptor. Journal of Endocrinological Investigation, 25, 959-966. [Google Scholar] [CrossRef
[44] Luo, L.-H., Li, D.-M., Wang, Y.-L., et al. (2017) Tim3/Galectin-9 Alleviates the Inflammation of TAO Patients via Suppressing Akt/NF-κB Signaling Pathway. Biochem-ical and Biophysical Research Communications, 491, 966-972. [Google Scholar] [CrossRef] [PubMed]
[45] Woeller, C.F., Roztocil, E., Hammond, C. and Feldon, S.E. (2019) TSHR Signaling Stimulates Proliferation through PI3K/Akt and Induction of miR-146a and miR-155 in Thyroid Eye Disease Orbital Fibroblasts. Investigative Ophthalmology & Visual Science, 60, 4336-4345. [Google Scholar] [CrossRef] [PubMed]
[46] Kumar, S., Nadeem, S., Stan, M.N., Coenen, M. and Bahn, R.S. (2011) A Stimulatory TSH Receptor Antibody Enhances Adipogenesis via Phosphoinositide 3-Kinase Activation in Orbital Preadipocytes from Patients with Graves’ Ophthalmopathy. Journal of Molecular Endocrinology, 46, 155-163. [Google Scholar] [CrossRef
[47] Li, B. and Smith, T.J. (2014) PI3K/AKT Pathway Mediates Induction of IL-1RA by TSH in Fibrocytes: Modulation by PTEN. The Journal of Clinical Endocrinology & Metabolism, 99, 3363-3372. [Google Scholar] [CrossRef] [PubMed]
[48] Zhu, J., Zhang, W., Zhang, Y., et al. (2018) Effects of Spica prunellae on Caspase-3-Associated Proliferation and Apoptosis in Human Lung Cancer Cells in Vitro. Journal of Cancer Research & Therapy, 14, 760-763. [Google Scholar] [CrossRef
[49] Johnson, G.L. (2011) Defining MAPK Interactomes. ACS Chem-ical Biology, 6, 18-20. [Google Scholar] [CrossRef] [PubMed]
[50] 仇莲胤, 阙华发. 甲状腺结节辨证分型标准的临床研究[J]. 上海中医药大学学报, 2013, 27(4): 26-30.