基于网络药理学与分子对接探讨参苓白术散对银屑病和肠道菌群紊乱“异病同治”的作用机制
Mechanism of Shenling Baizhu San in Treating Psoriasis and Intestinal Flora Disorders with Concept of “Same Treatment for Different Diseases” Based on Network Pharmacology and Molecular Docking Technology
DOI: 10.12677/acm.2025.15102949, PDF,    科研立项经费支持
作者: 黄雨桐*, 石 灿, 马天明#：黑龙江中医药大学附属第二医院皮肤科，黑龙江 哈尔滨；黑龙江中医药大学研究生院，黑龙江 哈尔滨
关键词: 参苓白术散；银屑病；肠道菌群；异病同治；肠–皮肤轴；Shenling Baizhu San； Psoriasis； Intestinal Flora； Same Treatment for Different Diseases； Gut-Skin Axis
摘要: 目的：以中医“异病同治”为理论依据，采用网络药理学方法探讨参苓白术散对银屑病和肠道菌群紊乱的作用机制。方法：通过中药系统药理学数据库与分析平台(TCMSP)检索获取参苓白术散复方活性成分及潜在靶点，利用GeneCards数据库获取疾病靶点，将两者取交集获取共有靶点。通过STRING11.5数据库构建蛋白质–蛋白质相互作用(PPI)网络。使用Cytoscape 3.9.0构建参苓白术散“成分–靶点–疾病”网络，获得参苓白术散异病同治的核心靶点。利用DAVID6.8数据库和微生信平台对核心靶点进行富集分析。结果：筛得疾病与药物共有靶点50个，核心靶点主要涉及原癌基因(RELA)、肿瘤坏死因子(TNF)、白细胞介素6 (IL6)、雌激素受体1 (ESR1)等，潜在靶点主要富集在癌症信号通路(pathways in cancer)，脂质与动脉粥样硬化(lipid and atherosclerosis)，流体剪切应力与动脉粥样硬化(fluid shear stress and atherosclerosis)等多条信号通路中。结论：参苓白术散中多种活性成分通过多靶点、多途径发挥抑制炎症反应、降低细胞凋亡作用、改善银屑病皮损、促进肠道微生态平衡、恢复肠道屏障的结构与功能的作用，初步揭示了参苓白术散“异病同治”银屑病和肠道菌群紊乱的潜在靶点与现代生物学机制，为深入研究开展实验及临床应用提供参考。
Abstract: Objective: To explore the mechanism of Shenling Baizhu San in treating psoriasis and intestinal flora disorders with the concept of “same treatment for different diseases” in traditional Chinese medicine (TCM) by network pharmacology. Methods: Searched Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to obtain the active ingredients and potential targets of Shenling Baizhu San, used GeneCards database to obtain the disease targets, and intersected the two to obtain the common targets. Constructed a protein-protein interaction (PPI) network using STRING11.5 database. Cytoscape 3.9.0 was used to construct the “component-target-disease” network of Shenling Baizhu San, to obtain the core targets of Shenling Baizhu San in treating psoriasis and intestinal flora disorders. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out by the DAVID6.8 database and the microbiology platform. Results: A total of 50 targets were screened, and the core targets were mainly related to proto-oncogenes (RELA), tumor necrosis factor (TNF), interleukin 6 (IL6), and estrogen receptor 1 (ESR1), etc. The potential targets were mainly enriched in pathways in cancer, lipid and atherosclerosis, and fluid shear stress and atherosclerosis, etc. Conclusion: The active ingredients in Shenling Baizhu San can inhibit inflammation, reduce apoptosis, improve psoriasis lesions, promote intestinal microecological balance, and restore the structure and function of intestinal barrier through multi-targets and multi-channels, which preliminarily revealed the potential targets and modern biological mechanisms of Shenling Baizhu San in treating psoriasis and intestinal flora disorders. And it will provide a reference for the in-depth study of experimental and clinical applications.
文章引用：黄雨桐, 石灿, 马天明. 基于网络药理学与分子对接探讨参苓白术散对银屑病和肠道菌群紊乱“异病同治”的作用机制[J]. 临床医学进展, 2025, 15(10): 1803-1814. https://doi.org/10.12677/acm.2025.15102949

参考文献

[1] Kulig, P., Musiol, S., Freiberger, S.N., Schreiner, B., Gyülveszi, G., Russo, G., et al. (2016) IL-12 Protects from Psoriasiform Skin Inflammation. Nature Communications, 7, Article No. 13466. [Google Scholar] [CrossRef] [PubMed]
[2] Armstrong, A.W. and Read, C. (2020) Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA, 323, 1945-1960. [Google Scholar] [CrossRef] [PubMed]
[3] 李楠, 王红梅, 冯剑, 等. 肠道菌群及其代谢产物SCFAs对银屑病发病机制的影响[J]. 医学综述, 2021, 27(20): 3977-3983.
[4] Park, D.H., Kim, J.W., Park, H. and Hahm, D. (2021) Comparative Analysis of the Microbiome across the Gut-Skin Axis in Atopic Dermatitis. International Journal of Molecular Sciences, 22, Article No. 4228. [Google Scholar] [CrossRef] [PubMed]
[5] Omenetti, S. and Pizarro, T.T. (2015) The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome. Frontiers in Immunology, 6, Article No. 639. [Google Scholar] [CrossRef] [PubMed]
[6] O’Neill, C.A., Monteleone, G., McLaughlin, J.T. and Paus, R. (2016) The Gut‐Skin Axis in Health and Disease: A Paradigm with Therapeutic Implications. BioEssays, 38, 1167-1176. [Google Scholar] [CrossRef] [PubMed]
[7] 张登本. 全注全译黄帝内经[M]. 北京: 新世界出版社, 2010.
[8] 刘朝霞, 韩晓冰, 张成会, 等. 运用健脾祛湿法治疗银屑病思路[J]. 中医杂志, 2012, 53(23): 2005-2006.
[9] 陈亚敏. 参苓白术散的临床应用[J]. 陕西中医, 2004(5): 460.
[10] 许树东. 银屑病治疗经验点滴[J]. 河南中医, 1994(6): 371.
[11] 刘凯文. 基于高通量测序探讨参苓白术散对脾气亏虚型泄泻肠道菌群的影响[D]: [硕士学位论文]. 北京: 北京中医药大学, 2020.
[12] Ipci, K., Altıntoprak, N., Muluk, N.B., Senturk, M. and Cingi, C. (2016) The Possible Mechanisms of the Human Microbiome in Allergic Diseases. European Archives of Oto-Rhino-Laryngology, 274, 617-626. [Google Scholar] [CrossRef] [PubMed]
[13] 涂晨, 王爽, 刘彦婷, 等. 银屑病患者肠道菌群多样性与表型分析[J]. 中国皮肤性病学杂志, 2021, 35(4): 397-404.
[14] 刘朝霞, 刘红霞. 刘红霞治疗寻常型银屑病经验[J]. 辽宁中医杂志, 2008(5): 670-671.
[15] Mlcek, J., Jurikova, T., Skrovankova, S. and Sochor, J. (2016) Quercetin and Its Anti-Allergic Immune Response. Molecules, 21, Article No. 623. [Google Scholar] [CrossRef] [PubMed]
[16] Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M., Wang, S., et al. (2016) Quercetin, Inflammation and Immunity. Nutrients, 8, Article No. 167. [Google Scholar] [CrossRef] [PubMed]
[17] Batiha, G.E., Beshbishy, A.M., Ikram, M., Mulla, Z.S., El-Hack, M.E.A., Taha, A.E., et al. (2020) The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin. Foods, 9, Article No. 374. [Google Scholar] [CrossRef] [PubMed]
[18] Haddad, P. and Eid, H. (2017) The Antidiabetic Potential of Quercetin: Underlying Mechanisms. Current Medicinal Chemistry, 24, 355-364. [Google Scholar] [CrossRef] [PubMed]
[19] Tang, S., Deng, X., Zhou, J., Li, Q., Ge, X. and Miao, L. (2020) Pharmacological Basis and New Insights of Quercetin Action in Respect to Its Anti-Cancer Effects. Biomedicine & Pharmacotherapy, 121, Article ID: 109604. [Google Scholar] [CrossRef] [PubMed]
[20] Sundarrajan, S., Nandakumar, M.P., Prabhu, D., Jeyaraman, J. and Arumugam, M. (2019) Conformational Insights into the Inhibitory Mechanism of Phyto-Compounds against Src Kinase Family Members Implicated in Psoriasis. Journal of Biomolecular Structure and Dynamics, 38, 1398-1414. [Google Scholar] [CrossRef] [PubMed]
[21] Chen, H., Lu, C., Liu, H., Wang, M., Zhao, H., Yan, Y., et al. (2017) Quercetin Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice via the NF-κB Pathway. International Immunopharmacology, 48, 110-117. [Google Scholar] [CrossRef] [PubMed]
[22] Qi, J., Yu, J., Li, Y., Luo, J., Zhang, C., Ou, S., et al. (2019) Alternating Consumption of β‐Glucan and Quercetin Reduces Mortality in Mice with Colorectal Cancer. Food Science & Nutrition, 7, 3273-3285. [Google Scholar] [CrossRef] [PubMed]
[23] Liu, C., Liu, H., Lu, C., Deng, J., Yan, Y., Chen, H., et al. (2019) Kaempferol Attenuates Imiquimod-Induced Psoriatic Skin Inflammation in a Mouse Model. Clinical and Experimental Immunology, 198, 403-415. [Google Scholar] [CrossRef] [PubMed]
[24] Bian, Y., Lei, J., Zhong, J., Wang, B., Wan, Y., Li, J., et al. (2022) Kaempferol Reduces Obesity, Prevents Intestinal Inflammation, and Modulates Gut Microbiota in High-Fat Diet Mice. The Journal of Nutritional Biochemistry, 99, Article ID: 108840. [Google Scholar] [CrossRef] [PubMed]
[25] Zhou, W., Hu, M., Zang, X., Liu, Q., Du, J., Hu, J., et al. (2020) Luteolin Attenuates Imiquimod-Induced Psoriasis-Like Skin Lesions in BALB/c Mice via Suppression of Inflammation Response. Biomedicine & Pharmacotherapy, 131, Article ID: 110696. [Google Scholar] [CrossRef] [PubMed]
[26] Bin Sayeed, M.S. and Ameen, S.S. (2015) Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight against Cancer. Nutrition and Cancer, 67, 1216-1222. [Google Scholar] [CrossRef] [PubMed]
[27] Thiele, J.J. and Ekanayake-Mudiyanselage, S. (2007) Vitamin E in Human Skin: Organ-Specific Physiology and Considerations for Its Use in Dermatology. Molecular Aspects of Medicine, 28, 646-667. [Google Scholar] [CrossRef] [PubMed]
[28] Liao, P., Lai, M., Hsu, K., Kuo, Y., Chen, J., Tsai, M., et al. (2018) Identification of β-Sitosterol as in Vitro Anti-Inflammatory Constituent in Moringa oleifera. Journal of Agricultural and Food Chemistry, 66, 10748-10759. [Google Scholar] [CrossRef] [PubMed]
[29] Yin, Y., Liu, X., Liu, J., Cai, E., Zhu, H., Li, H., et al. (2018) Beta-Sitosterol and Its Derivatives Repress Lipopolysaccharide/d-Galactosamine-Induced Acute Hepatic Injury by Inhibiting the Oxidation and Inflammation in Mice. Bioorganic & Medicinal Chemistry Letters, 28, 1525-1533. [Google Scholar] [CrossRef] [PubMed]
[30] Yates, M.E., Waltermire, H., Mori, K., Li, Z., Li, Y., Guzolik, H., et al. (2024) esr1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes. Endocrinology, 165, bqae111. [Google Scholar] [CrossRef] [PubMed]
[31] 孙鸽, 夏献民. RelA翻译后修饰对核因子κB活性的调控作用[J]. 临床与病理杂志, 2018, 38(4): 843-852.
[32] Rossi, J., Lu, Z., Jourdan, M. and Klein, B. (2015) Interleukin-6 as a Therapeutic Target. Clinical Cancer Research, 21, 1248-1257. [Google Scholar] [CrossRef] [PubMed]
[33] Saxena, A., Khosraviani, S., Noel, S., Mohan, D., Donner, T. and Hamad, A.R.A. (2015) Interleukin-10 Paradox: A Potent Immunoregulatory Cytokine That Has Been Difficult to Harness for Immunotherapy. Cytokine, 74, 27-34. [Google Scholar] [CrossRef] [PubMed]
[34] Doss C G, P. (2014) TNF/TNFR: Drug Target for Autoimmune Diseases and Immune-Mediated Inflammatory Diseases. Frontiers in Bioscience, 19, 1028-1040. [Google Scholar] [CrossRef] [PubMed]
[35] Cunningham, K.S. and Gotlieb, A.I. (2005) The Role of Shear Stress in the Pathogenesis of Atherosclerosis. Laboratory Investigation, 85, 9-23. [Google Scholar] [CrossRef] [PubMed]
[36] Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., et al. (1996) T Cell Interleukin-17 Induces Stromal Cells to Produce Proinflammatory and Hematopoietic Cytokines. The Journal of Experimental Medicine, 183, 2593-2603. [Google Scholar] [CrossRef] [PubMed]
[37] Huang, J., Lee, H., Zhao, X., Han, J., Su, Y., Sun, Q., et al. (2021) Interleukin-17d Regulates Group 3 Innate Lymphoid Cell Function through Its Receptor Cd93. Immunity, 54, 673-686.e4. [Google Scholar] [CrossRef] [PubMed]
[38] Krueger, J.G. (2012) Hiding under the Skin: A Welcome Surprise in Psoriasis. Nature Medicine, 18, 1750-1751. [Google Scholar] [CrossRef] [PubMed]

为你推荐