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基于转录组分析结合网络药理学探讨金黄膏治疗痤疮的作用机制及生物标志物研究

Identification of biomarkers of acne based on transcriptome analysis and combined with network pharmacology to explore the therapeutic mechanism of Jinhuang ointment.

机构信息

Shandong Women's University, Jinan City, Shandong Province, China.

Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, China.

出版信息

Medicine (Baltimore). 2023 Nov 3;102(44):e35642. doi: 10.1097/MD.0000000000035642.

Abstract

The incidence of acne is on the rise due to unhealthy diet and living habits. Jinhuang ointment (JHO) is a classic prescription composed of 10 kinds of commonly used Chinese herbal medicine, which has been widely used in clinical prevention and treatment of skin inflammatory diseases since ancient times. However, the pharmacological mechanism and target of JHO are not clear. The acne microarray dataset was downloaded from gene expression omnibus database to identify differentially expressed genes (DEG). Immune infiltration was analyzed by CiberSort algorithm. HUB gene was identified by protein-protein interaction network. The gene expression omnibus dataset validates the biomarkers of acne with high diagnostic value. The potential active components and targets of JHO were obtained through Traditional Chinese Medicine Systems Pharmacology database, and the therapeutic targets were obtained by crossing with disease targets. R-packet is used for enrichment analysis. Molecular docking using Auto Dock Tools. A total of 202 DEGs were identified from 12 skin samples in the GSE6475. Immune infiltration analysis showed that there were a large number of macrophages and mast cells in acne skin. Gene set enrichment analysis analysis showed that DEGS was mainly involved in bacterial reaction, inflammatory reaction and so on. Six central genes and gene cluster modules were identified by Cytoscape software. A total of 185 JHO active components and 220 targets were obtained, of which 10 targets were potential targets for JHO in the treatment of acne. Kyoto encyclopedia of genes and genomes enrichment analysis showed that JHO treatment of acne was mainly related to Toll-like receptors, IL-17 and other signal pathways. The results of molecular docking showed that 5 active compounds in JHO had strong binding activity to the core protein receptor. IL-1 β, CXCL8, toll-like receptor 2, CXCL2, LCN2, and secretory phosphoprotein 1 may be potential biomarkers for early diagnosis of acne. JHO active components may regulate skin cell metabolism and inflammatory response and improve cellular immune microenvironment by acting on core targets (CXCL8, ESR1, IL-1 β, MMP1, MMP3, secretory phosphoprotein 1), thus achieving the purpose of treating acne. This is the result of the joint action of multiple targets and multiple pathways. It provides an idea for the development of a new combination of drugs for the treatment of acne.

摘要

由于不健康的饮食和生活习惯,痤疮的发病率正在上升。金黄膏(JHO)是一种由 10 种常用中草药组成的经典方剂,自古以来就广泛应用于皮肤炎症性疾病的临床防治。然而,JHO 的药理机制和靶点尚不清楚。从基因表达综合数据库下载痤疮微阵列数据集,以鉴定差异表达基因(DEG)。通过 CiberSort 算法分析免疫浸润。通过蛋白质-蛋白质相互作用网络鉴定 HUB 基因。基因表达综合数据集验证了具有高诊断价值的痤疮生物标志物。通过中药系统药理学数据库获得 JHO 的潜在活性成分和靶点,并与疾病靶点交叉获得治疗靶点。使用 R 包进行富集分析。使用 Auto Dock Tools 进行分子对接。从 GSE6475 中的 12 个皮肤样本中鉴定出 202 个 DEG。免疫浸润分析表明,痤疮皮肤中有大量的巨噬细胞和肥大细胞。基因集富集分析分析表明,DEGS 主要参与细菌反应、炎症反应等。通过 Cytoscape 软件鉴定出 6 个中央基因和基因簇模块。共获得 185 个 JHO 活性成分和 220 个靶点,其中 10 个靶点可能是 JHO 治疗痤疮的潜在靶点。京都基因与基因组百科全书富集分析表明,JHO 治疗痤疮主要与 Toll 样受体、IL-17 等信号通路有关。分子对接结果表明,JHO 中的 5 种活性化合物与核心蛋白受体具有较强的结合活性。IL-1β、CXCL8、Toll 样受体 2、CXCL2、LCN2 和分泌性磷蛋白 1 可能是痤疮早期诊断的潜在生物标志物。JHO 活性成分可能通过作用于核心靶点(CXCL8、ESR1、IL-1β、MMP1、MMP3、分泌性磷蛋白 1)调节皮肤细胞代谢和炎症反应,改善细胞免疫微环境,从而达到治疗痤疮的目的。这是多个靶点和多个通路共同作用的结果。为开发治疗痤疮的新药组合提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4afd/10627606/c6a39ef72d61/medi-102-e35642-g001.jpg

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