基于网络药理学和分子对接技术预测泼尼松治疗口腔扁平苔藓的潜在靶点和分子机制

doi:10.13701/j.cnki.kqyxyj.2022.08.015

口腔医学研究 ›› 2022, Vol. 38 ›› Issue (8): 773-778.DOI: 10.13701/j.cnki.kqyxyj.2022.08.015

基于网络药理学和分子对接技术预测泼尼松治疗口腔扁平苔藓的潜在靶点和分子机制

王后赏, 杨津^*, 周红梅^*

口腔疾病研究国家重点实验室,国家口腔医学中心,国家口腔疾病临床研究中心,口腔医学⁺前沿医学创新中心,四川大学华西口腔医院四川成都 610041

收稿日期:2021-12-30 出版日期:2022-08-28 发布日期:2022-08-24
通讯作者: *杨津,E-mail: yangjin@scu.edu.cn;周红梅,E-mail: zhouhm@scu.edu.cn
作者简介:王后赏(1991~ ),女,河南驻马店人,硕士在读,主要从事口腔黏膜病相关临床和研究工作。
基金资助:
国家自然科学基金(编号:82101028、82071124)四川省科技计划(编号:2021YFH0143、2021YFS0194)

Prediction of Potential Targets and Molecular Mechanisms of Prednisone for Oral Lichen Planus Based on Network Pharmacology and Molecular Docking

WANG Houshang, YANG Jin^*, ZHOU Hongmei^*

State Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

Received:2021-12-30 Online:2022-08-28 Published:2022-08-24

摘要/Abstract

摘要： 目的: 联合采用网络药理学和分子对接技术,预测泼尼松治疗口腔扁平苔藓(oral lichen planus, OLP)的潜在靶点和分子机制。方法: (1)结合多种数据库预测泼尼松潜在作用靶点;(2)筛选OLP 相关疾病靶点;(3)构建药物和疾病交集靶点的PPI网络;(4)筛选网络中前20个关键靶点进行GO和KEGG富集分析;(5)分子对接分析。结果: (1)从多种数据库挖掘得到189个泼尼松潜在靶点;(2)获得552个OLP相关疾病靶点;(3)从构建的PPI网络筛选获得前20个关键靶蛋白;(4)对20个关键靶点的GO分析和KEGG分析结果表明,泼尼松可能通过调节PI3K-Akt、雌激素、丙型肝炎等信号通路发挥治疗作用;(5)分子对接分析结果表明,FN1、UBC和EGFR和泼尼松有良好的结合潜力。结论: 本研究预测获得泼尼松对OLP发挥治疗作用的潜在关键靶点及分子机制,这对促进靶向药物的研发及临床应用具有重要意义。

关键词: 口腔扁平苔藓, 泼尼松, 网络药理学, 分子对接, 分子靶点

Abstract: Objective: To explore the potential targets and molecular mechanisms of prednisone for oral lichen planus (OLP) by applying network pharmacology and molecular docking technology. Methods: (1) The potential targets of prednisone were predicted in multiple databases. (2) OLP-related targets were screened. (3) The PPI network was constructed for the intersection targets of drugs and diseases. (4) GO and KEGG enrichment analyses were performed for the top 20 targets in the PPI network. (5) Molecular docking was performed. Results: (1) A total of 189 potential targets of prednisone were obtained from various databases. (2) 552 OLP-related disease targets were found. (3) The top 20 key targets were screened from the PPI network. (4) GO and KEGG analysis of the 20 key targets indicated that prednisone may play a therapeutic role by regulating the PI3K-Akt signaling pathway, estrogen signaling pathway, hepatitis C pathway, et al. (5) Molecular docking showed that FN1, UBC, and EGFR had good binding potential with prednisone. Conclusion: The predicted potential key targets and molecular mechanisms of prednisone in treating OLP are of great significance for the development of new targeted drugs and clinical applications.

Key words: oral lichen planus, prednisone, network pharmacology, molecular docking, molecular targets

王后赏, 杨津, 周红梅. 基于网络药理学和分子对接技术预测泼尼松治疗口腔扁平苔藓的潜在靶点和分子机制[J]. 口腔医学研究, 2022, 38(8): 773-778.

WANG Houshang, YANG Jin, ZHOU Hongmei. Prediction of Potential Targets and Molecular Mechanisms of Prednisone for Oral Lichen Planus Based on Network Pharmacology and Molecular Docking[J]. Journal of Oral Science Research, 2022, 38(8): 773-778.

参考文献

[1] Hamour AF, Klieb H, Eskander A. Oral lichen planus [J]. CMAJ, 2020, 192(31): E892.
[2] 中华口腔医学会口腔黏膜病学专业委员会,中华口腔医学会中西医结合专业委员会.口腔扁平苔藓诊疗指南(试行)[J].中华口腔医学杂志,2012,47(7):399-401.
[3] Adcock IM, Mumby S. Glucocorticoids [J]. Handb Exp Pharmacol, 2017, 237: 171-196.
[4] Cain DW, Cidlowski JA. Immune regulation by glucocorticoids [J]. Nat Rev Immunol, 2017, 17(4): 233-247.
[5] Caplan A, Fett N, Rosenbach M, et al. Prevention and management of glucocorticoid-induced side effects: A comprehensive review: A review of glucocorticoid pharmacology and bone health [J]. J Am Acad Dermatol, 2017, 76(1): 1-9.
[6] Wang H, Zhou J, Guo X, et al. Use of glucocorticoids in the management of immunotherapy-related adverse effects [J]. Thorac Cancer, 2020, 11(10): 3047-3052.
[7] Song Y, Luo L, Wang K. Off-target identification by chemical proteomics for the understanding of drug side effects [J]. Expert Rev Proteomics, 2020, 17(10): 695-697.
[8] Luo TT, Lu Y, Yan SK, et al. Network pharmacology in research of Chinese medicine formula: methodology, application and prospective [J]. Chin J Integr Med, 2020, 26(1):72-80.
[9] Pinzi L, Rastelli G. Molecular docking: Shifting paradigms in drug discovery [J]. Int J Mol Sci, 2019, 20(18): 4331.
[10] UniProt Consortium. UniProt: a worldwide hub of protein knowledge [J]. Nucleic Acids Res, 2019, 47(D1): D506-D515.
[11] Burley SK, Bhikadiya C, Bi C, et al. RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences [J]. Nucleic Acids Res, 2021, 49(D1): D437-D451.
[12] Syriopoulou A, Markopoulos I, Tzakos AG, et al. Ligand-receptor interactions and drug design [J]. Methods Mol Biol, 2021, 2266: 89-104.
[13] Zhang L, Han L, Wang X, et al. Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking [J]. Biosci Rep, 2021, 41(6): BSR20203520.
[14] 郝民琦,王佳慧,李晓玲,等.基于网络药理学与分子对接探讨黄芪治疗溃疡性结肠炎的作用机制[J].中国药房,2021,32(10):1215-1223.
[15] Boezio B, Audouze K, Ducrot P, et al. Network-based approaches in pharmacology [J]. Mol Inform, 2017, 36(10): 1700048.
[16] Pompura SL, Dominguez-Villar M. The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function [J]. J Leukoc Biol, 2018, 103(6): 1065-1076.
[17] Chen F, Wei Z, Yin F, et al. Systemic and local changes of regulatory T cells in oral lichen planus [J]. Oral Dis, 2021.
[18] Cutolo M, Straub RH. Sex steroids and autoimmune rheumatic diseases: state of the art [J]. Nat Rev Rheumatol, 2020, 16(11): 628-644.
[19] Lavaee F, Bazrafkan N, Zarei F, et al. Follicular-stimulating hormone, luteinizing hormone, and prolactin serum level in patients with oral lichen planus in comparison to healthy population [J]. Biomed Res Int, 2021,2021: 8679505.
[20] Rotaru DI, Chisnoiu RM, Kui AI, et al. The influence of hepatitis C virus infection on ORAL health-related quality of life in patients with oral lichen planus [J]. Int J Environ Res Public Health, 2021, 18(17): 9382.
[21] Mester A, Lucaciu O, Ciobanu L, et al. Clinical features and management of oral lichen planus (OLP) with emphasis on the management of hepatitis C virus (HCV)-related OLP [J]. Bosn J Basic Med Sci, 2018, 18(3): 217-223.
[22] Lee KY, Nguyen HT, Setiawati A, et al. An extracellular matrix-liposome composite, a novel extracellular matrix delivery system for accelerated tissue regeneration [J]. Adv Healthc Mater, 2022, 11(4):e2101599.
[23] Núñez MA, de Matos FR, Freitas Rde A, et al. Immunohistochemical study of integrin α₅β₁, fibronectin, and Bcl-2 in normal oral mucosa, inflammatory fibroepithelial hyperplasia, oral epithelial dysplasia, and oral squamous cell carcinoma [J]. Appl Immunohistochem Mol Morphol, 2013, 21(4): 354-361.
[24] Sheng S, Guo B, Wang Z, et al. Aberrant methylation and immune microenvironment are associated with overexpressed fibronectin 1: A diagnostic and prognostic target in head and neck squamous cell carcinoma [J]. Front Mol Biosci, 2021, 8: 753563.
[25] Kattah MG, Malynn BA, Ma A. Ubiquitin-modifying enzymes and regulation of the inflammasome [J]. J Mol Biol, 2017, 429(22): 3471-3485.
[26] Abourehab MAS, Alqahtani AM, Youssif BGM, et al. Globally approved EGFR inhibitors: Insights into their syntheses, target kinases, biological activities, receptor interactions, and metabolism [J]. Molecules, 2021, 26(21): 6677.
[27] Ayati A, Moghimi S, Salarinejad S, et al. A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy [J]. Bioorg Chem, 2020, 99: 103811.
[28] Sabbah DA, Hajjo R, Sweidan K. Review on epidermal growth factor receptor (EGFR) structure, signaling pathways, interactions, and recent updates of EGFR inhibitors [J]. Curr Top Med Chem, 2020, 20(10): 815-834.
[29] Kumagai K, Horikawa T, Gotoh A, et al. Up-regulation of EGF receptor and its ligands, AREG, EREG, and HB-EGF in oral lichen planus [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010, 110(6): 748-754.
[30] Cortés-Ramírez DA, Rodríguez-Tojo MJ, Coca-Meneses JC, et al. Epidermal growth factor receptor expression in different subtypes of oral lichenoid disease [J]. Med Oral Patol Oral Cir Bucal, 2014, 19(5): e451-e458.

基于网络药理学和分子对接技术预测泼尼松治疗口腔扁平苔藓的潜在靶点和分子机制

Prediction of Potential Targets and Molecular Mechanisms of Prednisone for Oral Lichen Planus Based on Network Pharmacology and Molecular Docking

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