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整合网络药理学与实验验证以揭示碧萝芷的抗炎成分及分子机制。

Integrating network pharmacology and experimental verification to reveal the anti-inflammatory ingredients and molecular mechanism of pycnogenol.

作者信息

Liu Hongyu, Shi Jie, Liu Fei, Zhang Litao

机构信息

School of Biological Science, Jining Medical University, Rizhao, Shandong, China.

出版信息

Front Pharmacol. 2024 Jun 26;15:1408304. doi: 10.3389/fphar.2024.1408304. eCollection 2024.

DOI:10.3389/fphar.2024.1408304
PMID:38989153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11233470/
Abstract

Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined. This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments. 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1β to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. PYC could affect inflammation via multi-components, -targets, and -mechanisms.

摘要

碧萝芷(PYC)是一种从法国滨海松中提取的标准化提取物,传统上用于治疗炎症。然而,其主要活性成分及其作用机制尚未确定。本研究采用超高效液相色谱-串联质谱法(UPLC-MS/MS)和网络药理学来鉴定PYC的潜在活性成分,并通过细胞实验阐明其抗炎机制。鉴定出768种PYC化合物,筛选出19种抗炎化合物,其中85种靶蛋白直接参与炎症反应。蛋白质-蛋白质相互作用(PPI)分析确定白细胞介素6(IL6)、肿瘤坏死因子(TNF)、基质金属蛋白酶9(MMP9)、白细胞介素1β(IL1B)、蛋白激酶B1(AKT1)、干扰素γ(IFNG)、趋化因子配体8(CXCL8)、核因子κB亚基1(NFKB1)、趋化因子配体2(CCL2)、白细胞介素10(IL10)和前列腺素内过氧化物合酶2(PTGS2)为核心靶点。京都基因与基因组百科全书(KEGG)富集分析表明,PYC中的化合物可能通过白细胞介素17和肿瘤坏死因子信号通路发挥抗炎作用。细胞实验表明,PYC处理可降低脂多糖(LPS)诱导的BV2细胞中IL6和IL1β的表达,从而减轻炎症。PYC可能通过多成分、多靶点和多机制影响炎症反应。

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