基于网络药理学和分子对接技术分析紫珠叶洗剂促进创面愈合的作用机制

Analysis of the Mechanism of Action of Zizhuye Lotion in Promoting Wound Healing Based on Network Pharmacology and Molecular Docking Techniques

摘要:

目的：运用网络药理学结合分子对接技术分析紫珠叶洗剂促进创面愈合的作用机制。方法：通过TCMSP、HERB、PubChem、SwissTargetPrediction和UniProt数据库筛选紫珠叶洗剂的活性成分及作用靶点；检索GeneCards、OMIM数据库获得创面相关靶点；利用微生信平台获得交集靶点；采用Cytoscape3.9.1构建“药物-成分-靶点”网络；利用STRING和Cytoscape3.9.1构建蛋白互作（PPI） 网络；并对交集靶点进行基因本体（GO） 功能和京都基因与基因组百科全书（KEGG） 通路富集分析；选取度值较高的关键活性成分与核心靶点进行分子对接。结果：获得紫珠叶洗剂活性成分63个，作用靶点214个，创面相关靶点1 184个，紫珠叶洗剂促进创面愈合的潜在靶点106个。关键活性成分主要有槲皮素、β-谷甾醇、豆甾醇、3-辛酮和山柰酚等，核心靶点主要有白细胞介素-6 （IL-6）、肿瘤坏死因子（TNF）、白细胞介素-1β （IL-1β）、蛋白激酶B1 （AKT1）、肿瘤蛋白p53 （TP53） 等。GO 生物过程主要涉及RNA 聚合酶Ⅱ调控转录、基因通路的调控、DNA模板转录的调控、信号传导通路、凋亡信号通路的调控等，KEGG通路主要富集于糖尿病并发症中的晚期糖基化终末产物-受体（AGE-RAGE）、白细胞介素-17（IL-17）、TNF和磷脂酰肌醇3-激酶（PI3K） -Akt等信号通路。关键活性成分与核心靶点的分子对接结合能均＜0 kcal/mol。结论：紫珠叶洗剂能通过槲皮素、β-谷甾醇、豆甾醇、3-辛酮和山柰酚等活性成分作用于IL-1β、IL-6、AKT1、TNF 等靶点，调控AGE-RAGE、IL-17、TNF、PI3K-Akt等信号通路，调控炎症反应、加速细胞代谢和免疫调节等，加快细胞修复生成，促进创面愈合。

Abstract:

Abstract： Objective： To analyze the mechanism of action of Zizhuye Lotion in promoting wound healing using network pharmacology combined with molecular docking techniques. Methods： The active ingredients and action targets of Zizhuye Lotion were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， HERB， PubChem， SwissTargetPrediction， and UniProt databases. Wound-related targets were obtained from the GeneCards and OMIM databases. Intersection targets were screened using the bioinformatics platform. A "drug-component-intersection target" network was constructed using Cytoscape3.9.1. The STRING database and Cytoscape3.9.1 were used to construct a protein-protein interaction （PPI） network， and core targets were screened. Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed. Key active components with high degree values and core targets were selected for molecular docking. Results：A total of 63 active components，214 action targets，1 184 wound-related targets，and 106 potential targets of Zizhuye Lotion for promoting wound healing were identified. The key active components mainly included quercetin， β -sitosterol， stigmasterol， octan-3-one， and kaempferol. The core targets mainly included interleukin-6 （IL-6）， tumor necrosis factor （TNF）， interleukin-1β （IL-1β）， protein kinase B1 （AKT1）， and tumor protein p53 （TP53）. GO biological processes were mainly involved in the regulation of RNA polymerase Ⅱ transcription，regulation of gene pathways，regulation of DNA-templated transcription，signal transduction pathways， and regulation of apoptotic signaling pathways. KEGG pathways were mainly enriched in the advanced glycation end product （AGE）-receptor for AGE （RAGE） signaling pathway in diabetic complications， the interleukin-17（IL-17） signaling pathway，the TNF signaling pathway，and the phosphoinositide 3-kinase（ PI3K）-Akt signaling pathway. The binding energy of molecular docking between key active components and core targets was all less than 0 kcal/mol. Conclusion：Zizhuye Lotion can act on targets such as IL-1β，IL-6，AKT1，and TNF through active components including quercetin， β-sitosterol，stigmasterol，octan-3-one，and kaempferol，regulating signaling pathways such as AGE-RAGE，IL-17，TNF，and PI3K-Akt. It modulates inflammatory responses，accelerates cellular metabolism， and regulates immunity to promote cell repair and regeneration，thereby facilitating wound healing.