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Mechanisms of Dihuang(Rehmanniae Radix)in treating diabetic nephropathy complicated with depression based on network pharmacology 被引量:2
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作者 LEI Xing CHEN Qingyao +7 位作者 WANG Xiaoping XU Jie GAO Yazhen LIN Qiaohong ye zuwen ZHANG Jieyan SI Qin WANG Fang 《Digital Chinese Medicine》 2022年第2期178-188,共11页
Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanni... Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc. 展开更多
关键词 Dihuang(Rehmanniae Radix) Diabetic nephropathy DEPRESSION Network pharmacology Molecular docking Simultaneous treatment of different diseases True deficiency with false excess patterns Inflammation
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山蜡梅叶挥发油抗急性肺损伤的分子作用机制分析
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作者 徐杰 张小飞 +6 位作者 李风琴 林巧红 叶祖文 陈青垚 李嘉乐 王芳 杨明 《中国实验方剂学杂志》 CAS CSCD 北大核心 2023年第1期123-132,共10页
目的:基于网络药理学和分子对接技术对山蜡梅叶挥发油(CLO)治疗急性肺损伤(ALI)的作用机制进行预测,并通过建立ALI模型对其作用通路进行初步验证。方法:采用气相色谱-质谱法(GC-MS)对CLO进行成分分析;从PharmMapper和SwissTargetPredict... 目的:基于网络药理学和分子对接技术对山蜡梅叶挥发油(CLO)治疗急性肺损伤(ALI)的作用机制进行预测,并通过建立ALI模型对其作用通路进行初步验证。方法:采用气相色谱-质谱法(GC-MS)对CLO进行成分分析;从PharmMapper和SwissTargetPrediction数据库中获取其成分靶点,GeneCards、在线人类孟德尔遗传数据库(OMIM)和DisGeNET获取ALI相关靶点,与高通量基因表达数据库(GEO)获取的ALI差异表达基因(DEGs)在Venny 2.1.0平台上交集分析获得CLO抗ALI的潜在靶点;利用STRING 11.5对潜在靶点进行蛋白质-蛋白质相互作用(PPI)分析;从美国国家生物技术信息中心(NCBI)获取潜在靶点的组织表达情况并构建靶点组织分布图;运用RStudio 4.0.0软件对潜在靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;利用Cytoscape 3.9.1软件构建“成分-靶点-通路”网络图,筛选出关键成分和重点通路并进行分子对接验证;通过脂多糖(LPS)诱导建立ALI模型,测定大鼠血清中白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α的表达水平,免疫组化分析IL-17蛋白在ALI大鼠肺组织中的表达水平。结果:通过GC-MS鉴定出CLO的19个成分,经靶点筛选得到18个潜在靶点,PPI分析后得到15个具有相互作用关系的靶蛋白,进一步分析发现其在肺和胸腺等组织上高度表达,通过分析“成分-靶点-通路”网络图得到关键成分乙酸龙脑酯、芳樟醇、榄香醇、异丁酸香叶酯和核心靶点基质金属蛋白酶13(MMP13)、S100钙结合蛋白A9(S100A9)、脾酪氨酸激酶(SYK)及主要通路IL-17、TNF等;分子对接结果显示,CLO关键成分与IL-17信号通路的MMP13、S100A9结合稳定。药理实验结果证实CLO可以显著降低ALI大鼠血清中的IL-6和TNF-α含量,同时抑制大鼠肺组织中IL-17蛋白的表达水平。结论:CLO可以实现对ALI的治疗作用,保护肺组织,其作用机制可能与降低ALI大鼠血清中的IL-6和TNF-α表达水平、抑制肺组织中IL-17信号通路的活化有关。 展开更多
关键词 山蜡梅叶挥发油 网络药理学 急性肺损伤(ALI) 分子对接 白细胞介素(IL) 肿瘤坏死因子(TNF) 药理实验
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