基于网络药理学和临床试验验证的化湿行瘀清热方治疗口腔扁平苔藓的作用机制。
Mechanism of Huashi Xingyu Qingre recipe in treating oral lichen planus based on network pharmacology and clinical trial verification.
机构信息
Department of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Department of Stomatology, Hebei Children's Hospital, Shijiazhuang 050000, China.
出版信息
J Tradit Chin Med. 2022 Apr;42(2):304-313. doi: 10.19852/j.cnki.jtcm.20210707.001.
OBJECTIVE
To identify the main active components and targets of Huashi Xingyu Qingre recipe (, HXQR) and to investigate its mechanism in the treatment of oral lichen planus (OLP).
METHODS
The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was searched to identify the active ingredients and corresponding targets of HXQR. Disease genes were obtained from the GeneCards database, and a "drug-disease regulatory network" was constructed using Cytoscape software and PERL programming language. The STRING database was used to build a protein-protein interaction network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were analyzed using R software with a Bioconducter plugin. Finally, the results and the efficacy of HXQR in treating OLP were validated in a clinical trial that included enzyme-linked immunosorbent assay (ELISA) testing and observations of the post-treatment changes in clinical symptoms.
RESULTS
HXQR contained 167 active components and 261 targets, with 391 disease targets. The intersection of these two categories in a Venn diagram revealed 57 drug-disease common targets. A compound-target network was constructed and revealed that the six key pharmaceutical ingredients of HXQR were quercetin, luteolin, wogonin, kaempferol, beta-carotene, and baicalein. The protein-protein interaction network mainly involved core proteins such as ALB, interleukin-6, and AKT1. Drug-disease common targets were enriched in 1628 GO terms and 117 KEGG terms, mainly involving inflammatory responses, viral infections, and tumor-related pathways. ELISA testing indicated that HXQR inhibited the tumor necrosis factor (TNF) signaling pathway by reducing the expression of interleukin-6, matrix metalloproteinase-9, and intercellular adhesion molecule-1. The clinical symptoms of the patients with OLP were significantly improved after 8 weeks of treatment with HXQR.
CONCLUSION
HXQR treats OLP by regulating the TNF signaling pathway, resulting in a marked treatment effect with few adverse effects.
目的
鉴定化湿醒郁清热方（HXQR）的主要活性成分和靶点，并探讨其治疗口腔扁平苔藓（OLP）的作用机制。
方法
利用中药系统药理学数据库与分析平台（TCMSP）检索 HXQR 的活性成分和相应靶点。从 GeneCards 数据库中获取疾病基因，利用 Cytoscape 软件和 PERL 编程语言构建“药物-疾病调控网络”。利用 STRING 数据库构建蛋白质-蛋白质相互作用网络。利用 R 软件及其 Bioconducter 插件对基因本体（GO）和京都基因与基因组百科全书（KEGG）术语进行分析。最后，通过酶联免疫吸附测定（ELISA）检测和观察治疗后临床症状的变化，在临床试验中验证 HXQR 治疗 OLP 的疗效。
结果
HXQR 包含 167 个活性成分和 261 个靶点，与 391 个疾病靶点有交集。通过 Venn 图的交集发现 57 个药物-疾病共有靶点。构建化合物-靶点网络，发现 HXQR 的 6 种主要药用成分分别为槲皮素、木樨草素、汉黄芩素、山奈酚、β-胡萝卜素和黄芩素。蛋白质-蛋白质相互作用网络主要涉及核心蛋白，如 ALB、白细胞介素-6 和 AKT1。药物-疾病共有靶点富集了 1628 个 GO 术语和 117 个 KEGG 术语，主要涉及炎症反应、病毒感染和肿瘤相关途径。ELISA 检测表明，HXQR 通过降低白细胞介素-6、基质金属蛋白酶-9 和细胞间黏附分子-1 的表达，抑制肿瘤坏死因子（TNF）信号通路。经 HXQR 治疗 8 周后，OLP 患者的临床症状明显改善。
结论
HXQR 通过调节 TNF 信号通路治疗 OLP，疗效显著，不良反应少。
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