基于网络药理学的杜仲-山茱萸配伍治疗糖尿病的作用机制
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摘要
为探讨杜仲-山茱萸治疗糖尿病的作用机制。研究利用网络药理学的方法,首先通过中药系统药理学数据库筛选出杜仲和山茱萸的活性成分和相关靶点,再利用Dis Ge NET、Drug Bank等数据库筛选出糖尿病的潜在靶点。以STRING数据库对活性靶点构建蛋白互作网络(PPI)分析,采用Cytoscape 3.7.0软件绘制其"成分-靶点-通路"的相互作用网络,通过Cludter Profiler对靶蛋白进行生物过程、细胞组分及分子功能分析;京都基因与基因组(KEGG)的代谢通路分析。实验结果筛选得到杜仲-山茱萸有效成分30个,其中槲皮素、山奈酚、β-谷甾醇等成分对PTGS2、DPP4、ADRB2、PPARG等相关靶点通过IL-17信号通路、钙信号通路、脂肪细胞脂解的调控等参与氮化合物代谢过程、血液循环、脂肪细胞分化和血压调节等过程。综上,杜仲-山茱萸配伍治疗糖尿病存在多成分和多重药理作用机制,为进一步研究其治疗糖尿病药理实验提供了参考,也为其他中药的相关研究提供借鉴和参考。
In this study,the mechanism of Eucommia ulmoides and Cornus officinalis in the treatment of diabetes mellitus was studied by means of network pharmacology.Firstly,the active components and related targets of Eucommia ulmoides and Cornus officinalis were screened out by traditional Chinese medicine systematic pharmacological database,and then the potential targets of diabetes mellitus were screened out by Dis Ge NET,Drug Bank and other databases.The active target constructed protein interaction network(PPI) was analyzed by STRING database.The interaction network of " component,target and pathway" was drawn by Cytoscape 3.7.0 software,and the biological process of the target protein was carried out by Cludter Profiler.Cell composition and molecular function analysis;Metabolic pathway analysis of Kyoto gene and genomic(KEGG).The results showed that 30 active components of Eucommia ulmoides and Cornus officinalis were screened,in which quercetin,kaempferol and β-sitosterol were used to target PTGS2,DPP4,ADRB2,PPARG through IL-17 signaling pathway and calcium signaling pathway.The regulation of adiposis is involved in nitrogen metabolism,blood circulation,adipocytes differentiation and blood pressure regulation.In summary,there are multiple components and multiple pharmacological mechanisms in the treatment of diabetes mellitus with the combination of Eucommia ulmoides and Cornus officinalis,which provides a reference for further study on the pharmacological experiment of the treatment of diabetes mellitus,and also provides a reference for the related research of other traditional Chinese medicine.
In this study,the mechanism of Eucommia ulmoides and Cornus officinalis in the treatment of diabetes mellitus was studied by means of network pharmacology.Firstly,the active components and related targets of Eucommia ulmoides and Cornus officinalis were screened out by traditional Chinese medicine systematic pharmacological database,and then the potential targets of diabetes mellitus were screened out by Dis Ge NET,Drug Bank and other databases.The active target constructed protein interaction network(PPI) was analyzed by STRING database.The interaction network of " component,target and pathway" was drawn by Cytoscape 3.7.0 software,and the biological process of the target protein was carried out by Cludter Profiler.Cell composition and molecular function analysis;Metabolic pathway analysis of Kyoto gene and genomic(KEGG).The results showed that 30 active components of Eucommia ulmoides and Cornus officinalis were screened,in which quercetin,kaempferol and β-sitosterol were used to target PTGS2,DPP4,ADRB2,PPARG through IL-17 signaling pathway and calcium signaling pathway.The regulation of adiposis is involved in nitrogen metabolism,blood circulation,adipocytes differentiation and blood pressure regulation.In summary,there are multiple components and multiple pharmacological mechanisms in the treatment of diabetes mellitus with the combination of Eucommia ulmoides and Cornus officinalis,which provides a reference for further study on the pharmacological experiment of the treatment of diabetes mellitus,and also provides a reference for the related research of other traditional Chinese medicine.
引文
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2 Wu QH,Li BT,Xu J,et al.Research progress of compound chinese medicine in treating diabetes mellitus[J].China JChin Materia Med(中国中药杂志),2019,44:1104-1109.
3 Han MG,Li XH.Research progress of traditional chinese medicine in the treatment of early diabetic nephropathy[J].Chin Med Herald(中国医药导报),2018,15(29):42-45.
4 Zhang LH,Cui MC,Chen SJ.Anti-tumor mechanisms of radix puerariae based on network pharmacology[J].Nat Prod Res Dev(天然产物研究与开发),2018,30:547-553.
5 Chen QH,Li XF,Duan CC,et al.Study on the main active components and pharmacological mechanism of eucommia ulmoides by network pharmacology[J].Chin Med Mat(中药材),2018,41:419-426.
6 Tu YC,Lian TW,Yen JH,et al.Antiatherogenic effects of kaempferol and rhamnocitrin[J].J Agr Food Chem,2007,55:9969-9976.
7 Fang XK,Gao J,Zhu DN,et al.Kaempferol and quercetin isolated from euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity[J].Life Sci,2008,82:620-622.
8 Xing J,Yu ZL,Zhang XY,et al.Epicatechin alleviates inflammation in lipopolysaccharide-induced acute lung injury in mice by inhibiting the P38 MAPK signaling pathway[J].Int Immunopharmacol,2019,66:146-153.
9 Han T,Lyu Y,Wang S,et al.PPAR(overexpression regulates cholesterol metabolism in human L02 hepatocytes[J].JPharmacol Sci,2018,139(1):1-8.
10 Tontonoz P,Hu E,Spiegelman BM,et al.Stimulation of adipogenesis in fibroblasts by PPARγ2,a lipid-activated transcription factor[J].Cell,1994,79:1147-1156.
11 Ben S,Cooper-dehoff RM,Flaten HK,et al.Multiplex SNa P-shot-a new simple and efficient CYP2D6 and ADRB1genotyping method[J].Hum Genomics,2016,10(1):11.
12 Vane JR,Mitchell JA,Appleton I,et al.Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation[J].P Natl Acad Sci,1994,91:2046-2050.
13 Tseng HC,Lin CC,Wang CY,et al.Lysophosphatidylcholine induces cyclooxygenase-2-dependent IL-6 expression in human cardiac fibroblasts[J].Cell Mol Life Sci,2018,75:4599-4617.
14 Bockaert J,Claeysen S,Carine B,et al.Neuronal 5-HTmetabotropic receptors:fine-tuning of their structure,signaling,and roles in synaptic modulation[J].Cell Tissue Res,2006,326:553-572.
15 Arner P,Langin D.Lipolysis in lipid turnover,cancer cachexia,and obesity-induced insulin resistance[J].Trends Endocrin Met,2014,25:255-262.
16 Ahmadian M,Wang Y,Sul HS,et al.Lipolysis in adipocytes[J].Int J Biochem Cell B,2010,42:550-559.
17 Kidoya H,Ueno M,Yamada Y,et al.Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis[J].Embo J,2014,27:522-534.
18 Pernaute B,Spruce T,Smith KM,et al.MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM[J].Gene Dev,2014,28:1873-1878.
19 Zhu XJ,Song BJ,Yang YH,et al.Effects of resveratrol on blood glucose and antioxidant enzymes in type 2 diabetic rats[J].Chin J Diabetes(中国糖尿病杂志),2013,21:947-949.
20 Thayer TC,Delano M,Liu C,et al.Superoxide production by macrophages and T cells is critical for the induction of autoreactivity and type 1 diabetes[J].Diabetes,2011,60:2144-2151.