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基于网络药理学探讨黄芩–夏枯草–金银花治疗子宫内膜异位症的作用机制
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Abstract:
目的：基于网络药理学的方法探讨中药黄芩–夏枯草–金银花治疗子宫内膜异位症的作用机制。方法：使用中药系统药理学数据库与分析平台(TCMSP)搜索黄芩、夏枯草及金银花的有效活性成分及作用靶点，通过GeneCards、OMIM和DisGeNet数据库筛选子宫内膜异位症疾病的相关靶点。使用Venny 2.1在线工具构建黄芩–夏枯草–金银花作用靶点与子宫内膜异位症疾病靶点韦恩图，获得交集靶点基因。利用Cytoscape 3.7.1软件对药物–成分–交集靶点网络进行可视化构建，同时将获得的交集靶点基因上传至STRING网站进行蛋白质–蛋白质相互作用分析，使用Metascape在线分析平台对交集靶点进行GO富集分析与KEGG通路富集分析。结果：筛选获得黄芩–夏枯草–金银花的有效活性成分共52个，黄芩–夏枯草–金银花与子宫内膜异位症交集靶点有140个，相关重要靶点包括AKT1、TNF、IL6、TP53、IL1B等。GO富集分析结果显示涉及1878个生物过程，76个细胞组分，196个分子功能。KEGG通路富集获得205条相关信号通路，主要涉及的通路有PI3K-Akt信号通路、IL-17信号通路、TNF信号通路等。结论：黄芩–夏枯草–金银花可能通过多靶点、多通路发挥治疗子宫内膜异位症的作用。
Objective: To explore the mechanism of action of traditional Chinese medicine Scutellariae Radix-Spica Prunellae-Lonicerae Japonicae Flos in the treatment of endometriosis based on network pharmacology. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to search for effective active ingredients and targets of Scutellariae Radix, Spica Prunellae, Lonicerae Japonicae Flos, and related targets for endometriosis diseases were screened through GeneCards, OMIM and DisGeNet databases. Use the Venny 2.1 online tool to construct a Venn diagram of Scutellariae Radix-Spica Prunellae-Lonicerae Japonicae Flos action targets and endometriosis disease targets, and obtain intersection target genes. Cytoscape 3.7.1 software was used to visually construct the drug-component-intersection target network, and the obtained intersection target genes were uploaded to the STRING website for protein-protein interaction analysis. The Metascape online analysis platform was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on the intersection targets. Results: A total of 52 effective active ingredients of Scutellariae Radix-Spica Prunellae-Lonicerae Japonicae Flos were screened, and there were 140 intersection targets between Scutellariae Radix-Spica Prunellae-Lonicerae Japonicae Flos and endometriosis. Related important targets include AKT1, TNF, IL6, TP53, IL1B, etc. GO enrichment analysis results showed that 1878 biological processes, 76 cellular components, and 196 molecular functions were involved. KEGG pathway enrichment obtained 205 related signaling pathways, the main pathways involved include the PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway, etc. Conclusion: Scutellariae Radix-Spica Prunellae-Lonicerae Japonicae Flos may play a role in treating
| [1] | Taylor, H.S., Kotlyar, A.M. and Flores, V.A. (2021) Endometriosis Is a Chronic Systemic Disease: Clinical Challenges and Novel Innovations. The Lancet, 397, 839-852. https://doi.org/10.1016/s0140-6736(21)00389-5 |
| [2] | 宋景艳, 孙振高, 王爱娟, 等. 中药复方改善子宫内膜异位症相关性不孕症妊娠率的系统评价[J]. 世界中西医结合杂志, 2017, 12(1): 18-22. |
| [3] | 李伟, 贾志春, 徐伟, 等. 黄芩的化学成分、药理作用以及临床应用[J]. 山西大同大学学报(自然科学版), 2024, 40(5): 85-90. |
| [4] | Wen, Y., Wang, Y., Zhao, C., Zhao, B. and Wang, J. (2023) The Pharmacological Efficacy of Baicalin in Inflammatory Diseases. International Journal of Molecular Sciences, 24, Article 9317. https://doi.org/10.3390/ijms24119317 |
| [5] | Ning, N., Nan, Y., Chen, G., Huang, S., Lu, D., Yang, Y., et al. (2024) Anti-Tumor Effects and Toxicity Reduction Mechanisms of Prunella Vulgaris: A Comprehensive Review. Molecules, 29, Article 1843. https://doi.org/10.3390/molecules29081843 |
| [6] | Liu, C., Xu, M., Yan, L., Wang, Y., Zhou, Z., Wang, S., et al. (2021) Honeysuckle-Derived MicroRNA2911 Inhibits Tumor Growth by Targeting TGF-β1. Chinese Medicine, 16, Article No. 49. https://doi.org/10.1186/s13020-021-00453-y |
| [7] | 宁承洁, 余洁. 基于国家专利的中药复方治疗子宫内膜异位症的用药规律研究用[J]. 中医临床研究, 2022, 14(19): 7-11. |
| [8] | Zhang, P., Zhang, D., Zhou, W., Wang, L., Wang, B., Zhang, T., et al. (2023) Network Pharmacology: Towards the Artificial Intelligence-Based Precision Traditional Chinese Medicine. Briefings in Bioinformatics, 25, bbad518. https://doi.org/10.1093/bib/bbad518 |
| [9] | Simoens, S., Dunselman, G., Dirksen, C., Hummelshoj, L., Bokor, A., Brandes, I., et al. (2012) The Burden of Endometriosis: Costs and Quality of Life of Women with Endometriosis and Treated in Referral Centres. Human Reproduction, 27, 1292-1299. https://doi.org/10.1093/humrep/des073 |
| [10] | Nnoaham, K.E., Hummelshoj, L., Webster, P., d’Hooghe, T., de Cicco Nardone, F., de Cicco Nardone, C., et al. (2011) Impact of Endometriosis on Quality of Life and Work Productivity: A Multicenter Study across Ten Countries. Fertility and Sterility, 96, 366-373.e8. https://doi.org/10.1016/j.fertnstert.2011.05.090 |
| [11] | De Graaff, A.A., D'Hooghe, T.M., Dunselman, G.A.J., Dirksen, C.D., Hummelshoj, L., Simoens, S., et al. (2013) The Significant Effect of Endometriosis on Physical, Mental and Social Wellbeing: Results from an International Cross-Sectional Survey. Human Reproduction, 28, 2677-2685. https://doi.org/10.1093/humrep/det284 |
| [12] | Vercellini, P., Barbara, G., Abbiati, A., Somigliana, E., Viganò, P. and Fedele, L. (2009) Repetitive Surgery for Recurrent Symptomatic Endometriosis: What to Do? European Journal of Obstetrics & Gynecology and Reproductive Biology, 146, 15-21. https://doi.org/10.1016/j.ejogrb.2009.05.007 |
| [13] | Saraswat, L., Ayansina, D., Cooper, K., Bhattacharya, S., Horne, A. and Bhattacharya, S. (2017) Impact of Endometriosis on Risk of Further Gynaecological Surgery and Cancer: A National Cohort Study. BJOG: An International Journal of Obstetrics & Gynaecology, 125, 64-72. https://doi.org/10.1111/1471-0528.14793 |
| [14] | Ng, S., Norwitz, S.G., Taylor, H.S. and Norwitz, E.R. (2020) Endometriosis: The Role of Iron Overload and Ferroptosis. Reproductive Sciences, 27, 1383-1390. https://doi.org/10.1007/s43032-020-00164-z |
| [15] | 胡晓英, 吴建发, 王鹰, 等. 汉黄芩素调节SIRT1/Nrf2信号通路对子宫内膜异位症大鼠铁死亡的影响[J]. 遵义医科大学学报, 2023, 46(10): 943-949. |
| [16] | 尹家军, 程凯. 夏枯草对甲状腺疾病的影响研究[J]. 系统医学, 2024, 9(23): 195-198. |
| [17] | 李世大, 刘丽. 刘丽教授治疗妇科疾病常用药对举隅[J]. 长春中医药大学学报, 2013, 29(4): 613-614. |
| [18] | 张军, 万淑琼. 黄芩素治疗子宫内膜异位症的作用研究[J]. 时珍国医国药, 2007, 18(4): 895-897. |
| [19] | Lee, Y., Lee, J. and Lim, C. (2021) Anticancer Activity of Flavonoids Accompanied by Redox State Modulation and the Potential for a Chemotherapeutic Strategy. Food Science and Biotechnology, 30, 321-340. https://doi.org/10.1007/s10068-021-00899-8 |
| [20] | 张曦, 王鑫, 王红静, 等. 槲皮素对子宫内膜异位症的抑制作用及机理探讨[J]. 四川大学学报: 医学版, 2009, 40(2): 228-231, 244. |
| [21] | 郑汝群, 宋金龙, 刘华, 等. Akt水平在PCOS患者中的变化及与胰岛素抵抗的相关性研究进展[J]. 中国妇幼保健, 2020, 35(5): 966-968. |
| [22] | 王纪元, 索青霞, 成丽, 等. 肿瘤坏死因子抑制剂治疗子宫内膜异位症的研究进展[J]. 浙江医学, 2019, 41(21): 2335-2338. |
| [23] | Mosbah, A., Nabiel, Y. and Khashaba, E. (2016) Interleukin‐6, Intracellular Adhesion Molecule‐1, and Glycodelin a Levels in Serum and Peritoneal Fluid as Biomarkers for Endometriosis. International Journal of Gynecology & Obstetrics, 134, 247-251. https://doi.org/10.1016/j.ijgo.2016.01.018 |
| [24] | Massarotti, C., Mirabelli Badenier, I., Paudice, M., Scaglione, G., Remorgida, V. and Vellone, V.G. (2021) Steroids Receptors Immunohistochemical Expression in Different Sites of Endometriosis. Journal of Gynecology Obstetrics and Human Reproduction, 50, Article ID: 101861. https://doi.org/10.1016/j.jogoh.2020.101861 |
| [25] | 黄卓雅, 廖鹏娟, 黄楚楚, 等. EGFR、GPER在子宫内膜异位症组织中表达及其相关性[J]. 中国计划生育学杂志, 2021, 29(7): 1378-1382. |
| [26] | 王静, 王燕, 杜欣, 等. 萝卜硫素通过P13K/Akt信号通路对腹腔子宫内膜异位症大鼠的保护作用[J]. 临床和实验医学杂志, 2019, 18(20): 2176-2180. |
| [27] | 李燕, 朱君, 张煜. P13K/AKT信号转导通路和VEGF在子宫内膜异位症中的表达[J]. 中国性科学, 2017, 26(4): 45-47. |
| [28] | Shi, J., Zheng, Z., Chen, M., Shen, H., Li, M. and Shao, J. (2022) IL-17: An Important Pathogenic Factor in Endometriosis. International Journal of Medical Sciences, 19, 769-778. https://doi.org/10.7150/ijms.71972 |
| [29] | 王鹰, 余震, 吴建发, 等. 消瘤方对子宫内膜异位症盆腔粘连大鼠粘连组织中TLR4/NF-κB/TNF-α信号通路表达的影响[J]. 中国性科学, 2022, 31(3): 136-140. |
