摘要
该研究利用TCMSP数据库和Swiss Target Prediction平台获取臻呼畅组合物(简称SSD)中各中药的活性成分和靶点,利用GeneCards、DisGeNET、GEO数据库获取急性肺损伤相关靶点。通过Cytoscape 3.9.1软件、STRING数据库构建中药-活性成分-靶点-疾病网络、PPI网络,筛选出核心成分和核心靶点。利用David数据库对关键靶点进行GO和KEGG分析。应用AutoDock Vina 1.2.3软件对核心成分和核心靶点进行分子对接,PyMOL 2.6.0软件进行可视化处理。采用脂多糖(LPS)诱导的急性肺损伤(Acute lung injury,ALI)大鼠模型,验证SSD改善急性肺损伤的作用。结果表明:筛选出SSD活性成分30个,改善肺损伤相关靶点9个,其中核心成分主要为β-谷甾醇(β-sitosterol)、亚油酸乙酯(mandenol)、山奈酚(kaempferol)、26-O-β-D-glucopyranosyl-3β,26-dihydroxy-5-cholesten-16,22-dioxo-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside_qt,核心靶点主要为白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子(Tumor necrosis factor,TNF)、环加氧酶-2(prostaglandin-endoperoxide synthase 2,PTGS2)、Jun原癌基因(Jun proto-oncogene,JUN)、纤溶酶原激活物抑制因子-1(Serpin E1,SERPINE1)。GO和KEGG分析结果显示,SSD主要通过白细胞介素-8(Interleukin-8,IL-8)生成的正向调节、白细胞与血管内皮细胞粘附、脂多糖反应、血管内皮生长因子产生,与蛋白酶结合、IL-6受体结合、转录调控区序列特异性DNA结合,调控糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路等协同发挥改善急性肺损伤的作用。分子对接证明3个核心成分与5个核心靶点均结合良好。动物实验结果表明中高剂量的臻呼畅组合物可显著降低ALI大鼠肺泡灌洗液、肺组织中的炎症因子TNF-α、IL-1β和IL-10水平,病理学观察其可减轻肺组织损伤。该研究初步揭示了臻呼畅组合物改善急性肺损伤的多成分、多靶点、多途径的协同作用机制,为SSD应用于肺部健康的保健及ALI的预防提供理论依据。
In this study,the active ingredients and potential targets of each Traditional Chinese Medicine(TCM)in SSD compound were obtained from the TCMSP database and Swiss Target Prediction online prediction platform,while GeneCards,DisGeNET,and GEO databases were used to obtain the acute lung injury related(ALI)targets.The TCM-active ingredient-target-disease network and PPI network were constructed by using Cytoscape 3.9.1 software and the STRING database,and the core ingredients and targets were subsequently screened.GO and KEGG analysis of core targets were performed by the David database.Molecular docking of core ingredients and core targets was performed using AutoDock Vina 1.2.3 software,and the result was visualized by PyMOL 2.6.0.Finally,the lipopolysaccharide(LPS)induced ALI rat model was established to verify the effect of SSD on ALI.The results showed that 30 active ingredients of SSD were screened,and 9 ALI improvement related targets were identified,among which the main core ingredients wereβ-sitosterol,mandenol,kaempferol,and 26-O-β-D-glucopyranosyl-3β,26-dihydroxy-5-cholesten-16,22-dioxo-3-O-α-Lrhamnopyranosyl-(1→2)-β-D-glucopyranoside_qt,the main core targets were interleukin-6(IL-6),tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),Jun proto-oncogene(JUN),and serpin E1(SERPINE1).GO and KEGG analysis showed that SSD improved ALI through multiple biological processes,such as positive regulation of interleukin-8 production,leukocyte adhesion to vascular endothelial cell,cellular response to lipopolysaccharide,vascular endothelial growth factor production,protease binding,interleukin-6 receptor binding,transcription regulatory region sequence-specific DNA binding,regulation of AGE-RAGE signaling pathway and TNF signaling pathway in diabetic complications and other ways,these can play a synergistic role in improving ALI.Molecular docking results showed that all 3 core components were well combined with the 5 core targets.The results of animal experiments showed that medium and high dose of SSD could significantly reduce the levels of inflammatory factors TNF-α,IL-1βand IL-10 in bronchoalveolar lavage fluid and lung tissue of ALI rats,further pathological observation also showed that SSD could alleviate lung tissue injury.This study initially reveals that SSD improves ALI by the combined action of multiple components,multiple targets,and multiple pathways,which provides a theoretical basis for the application of SSD in lung health care and the prevention of ALI.
作者
陈石生
叶健文
严建刚
欧阳道福
李晓敏
毛新亮
CHEN Shisheng;YE Jianwen;YAN Jiangang;OUYANG Daofu;LI Xiaomin;MAO Xinliang(Perfect(Guangdong)Co.,Ltd.,Zhongshan 528400,China)
出处
《食品与发酵科技》
CAS
2024年第5期44-55,共12页
Food and Fermentation Science & Technology
基金
中山市科技创新领军人才资助项目(LJ2021007)。
关键词
橘红
鱼腥草
急性肺损伤
网络药理学
分子对接
作用机制
Citrus reticulata Blanco
Houttuynia cordata
acute lung injury(ALI)
network pharmacology
molecular docking
mechanism
