基于化合物与蛋白互作分析根皮苷的降糖机制
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摘要
目的:以根皮苷为对象,分析根皮苷在分子层面的降糖机制。方法:通过Stitch和ChEMBL网络数据库检索获得根皮苷的作用靶点及蛋白互作信息,利用分子复合物检测算法(MCODE)对网络进行模块分析及功能注释。结果:从数据库中筛选出21个靶点,构建的蛋白互作网络中有170个节点和545条边,通过聚类分析得到10个功能模板,模块分析表明,根皮苷主要参与组蛋白乙酰化、血糖稳态、乙酰胆碱分解、戊糖降解、嘌呤核苷酸阴离子转运、钙离子稳态等生物过程,发挥降糖作用。结论:本研究从分子网络水平分析了根皮苷的降糖机制,为糖尿病的治疗提供新途径。
Objective:Phloridzin was employed as the research object,and the hypoglycemic effect on molecular level was analyzed. Methods:Phloridzin was chosen in this study to obtain the targets of the components and protein-protein information though Stitch and ChEMBL databases retrieval. Module analysis and function annotation of network were analyzed by a graph theoretic clustering algorithm molecular complex detection(MCODE). Results:21 targets were screened from database. There were 170 nodes and 545 deges in the protein interaction network. 10 function modules were obtained from cluster analysis. Hypoglycemic effect of phloridzin was mainly associated with histone acetylation,glucose homeostasis,acetylcholine catabolic process,pentose catabolic process,purine nucleoside transport,anion transport,calcium ion homeostasis. Conclusion:In this study,the anti-diabetes mechanism of phloridzin was elucidated systematically from molecular network level,which provided new approaches for the treatment of diabetes.
Objective:Phloridzin was employed as the research object,and the hypoglycemic effect on molecular level was analyzed. Methods:Phloridzin was chosen in this study to obtain the targets of the components and protein-protein information though Stitch and ChEMBL databases retrieval. Module analysis and function annotation of network were analyzed by a graph theoretic clustering algorithm molecular complex detection(MCODE). Results:21 targets were screened from database. There were 170 nodes and 545 deges in the protein interaction network. 10 function modules were obtained from cluster analysis. Hypoglycemic effect of phloridzin was mainly associated with histone acetylation,glucose homeostasis,acetylcholine catabolic process,pentose catabolic process,purine nucleoside transport,anion transport,calcium ion homeostasis. Conclusion:In this study,the anti-diabetes mechanism of phloridzin was elucidated systematically from molecular network level,which provided new approaches for the treatment of diabetes.
引文
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[31]刘勇华,刘丹,夏春华.OATP遗传多态对口服降糖药及调血脂药转运的影响及可能的相互作用机制研究[J].江西医药,2017,52(6):576-578.
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[33]刘莹,王淑秋,李喆.2型糖尿病大鼠肾脏的钙稳态失衡、细胞色素C的变化与灵芝孢子粉的干预[J].中国老年学杂志,2009,29(3):267-269.
[34]吕俊华,杨文豪,沈文娟,等.绿茶多酚对D-半乳糖与Aβ25～35诱导Alzheimer病小鼠抗氧化能力和钙稳态的影响[J].中国老年学杂志,2006,26(8):1093-1095.
[2]Chamberlain J J,Herman W H,Leal S,et al.Pharmacologic therapy for type 2 diabetes:Synopsis of the 2017 American diabetes association standards of medical care in diabetes[J].Annals of Internal Medicine,2017,166(8):542-552.
[3]Ran J,Sun H,Xu Y,et al.Comparison of antioxidant activities and high-performance liquid chromatography analysis of polyphenol from different apple varieties[J].International Journal of Food Properties,2016,19(11):2396-2407.
[4]Fromm M,Bayha S,Carle R,et al.Characterization and quantitation of low and high molecular weight phenolic compounds in apple seeds[J].Journal of Agricultural and Food Chemistry,2012,60(5):1232-1242.
[5]Pei F,Li B Y,Zhang Z,et al.Beneficial effect of phlorizin on diabetic nephropathy in diabetic db/db mice[J].Journal of Diabetes and Its Complications,2014,28(5):596-603.
[6]Wang Q,Qiu L,Chen X R,et al.Inhibitory effects of phloridzin dihydrate on the activity of mushroom(Agaricus bisporus)tyrosinase[J].Bioorganic & Medicinal Chemistry,2007,15(3):1568-1571.
[7]Ehrenkranz J R L,Lewis N G,Kahn C R,et al.Phlorizin:A review[J].Diabetes/Metablism Research Reviews,2005,21(1):31-38.
[8]Lemoine R,Delrot S.Recognition of phlorizin by the carriers of sucrose and hexose in broad bean leaves[J].Physiologia Plantarum,1987,69(4):639-644.
[9]任真真,张燕玲,王星,等.三七皂苷类成分的蛋白质相互作用网络分析[J].中国中药杂志,2014,39(11):2097-2101.
[10]霍梦琪,张燕玲,郑世超,等.基于共表达蛋白相互作用网络探讨川芎嗪治疗冠心病的机制[J].北京中医药大学学报,2016,39(12):989-997.
[11]Assenov Y.Computing topological parameters of biological networks[J].Bioinformatics,2008,24(2):282-284.
[12]Lobingier B T,Hüttenhain R,Eichel K,et al.An approach to spatiotemporally resolve protein interaction networks in living cells[J].Cell,2017,169(2):350-360.
[13]Yang W,Schuster C,Beahan C T,et al.Regulation of meristem morphogenesis by cell wall synthases in arabidopsis[J].Current Biology,2016,26(11):1404-1415.
[14]王燕飞,候粲,苏欣,等.组蛋白乙酰化与糖尿病[J].中华内分泌代谢杂志,2014,30(2):167-170.
[15]侯粲,赵明,李霞,等.2型糖尿病患者外周血单个核细胞组蛋白乙酰化研究[J].中华内分泌代谢杂志,2012,28(3):183-185.
[16]Kissa A K,Stolarczyk M,Melzig M F.Epigenetic modulation of mechanisms involved in inflammation:Influence of selected polyphenolic substances on histone acetylation state[J].Food Chemistry,2012,131(3):1015-1020.
[17]Rosenstock J,Cefalu W T,Lapuerta P,et al.Greater dose-ranging effects on A1C levels than on glucosuria with LX4211,a dual inhibitor of SGLT1 and SGLT2,in patients with type 2 diabetes on metformin monotherapy[J].Diabetes Care,2015,38(3):431-438.
[18]Walle T,Walle U K.The beta-D-glucoside and sodium-dependent glucose transporter 1(SGLT1)-inhibitor phloridzin is transported by both SGLT1 and multidrug resistance-associated proteins 1/2[J].Drug Metabolism & Disposition,2003,31(11):1288-1291.
[19]赵晓云,邢邯英,裴华颖,等.内源性一氧化碳在糖尿病大鼠股动脉舒张反应障碍中的作用[J].北京大学学报:医学版,2005,37(4):389-392.
[20]王晓兵.辣椒素对2型糖尿病大鼠冠状动脉内皮依赖性舒张功能的影响[J].中国糖尿病杂志,2017,9(2):116-121.
[21]张颖,李赛,丁选胜.淫羊藿苷对糖尿病肾病大鼠肾动脉舒缩功能的影响[J].药学与临床研究,2016,24(3):209-211.
[22]Rizzoni D,Porteri E,Guelfi D,et al.Structural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus[J].Circulation,2016,103(9):1238-1244.
[23]高文波,陈武,翁国斌,等.绿茶多酚减轻环孢素A致血管收缩和肾毒性的实验研究[J].浙江医学,2010,32(8):1205-1208.
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[27]蔡晓凌,陈祎霏,韩斐斐,等.高尿酸血症与2型糖尿病[J].中国心血管杂志,2016,21(1):8-10.
[28]Ioachimescu A G,Hampstead B M,Moore A,et al.Growth hormone deficiency after mild combat-related traumatic brain injury[J].Pituitary,2015,18(4):535-541.
[29]Dyer E M,Amin R.Fifteen-minute consultation:Monogenic forms of diabetes with onset after age 6 months[J].Archives of Disease in Childhood Education and Practice,2018,103(2):58-64.
[30]Liu J R,Liu B W,Yin F Z.Change in nonhigh-density lipoprotein cholesterol levels in adults with prediabetes[J].Medicine,2017,96(44):e8461.
[31]刘勇华,刘丹,夏春华.OATP遗传多态对口服降糖药及调血脂药转运的影响及可能的相互作用机制研究[J].江西医药,2017,52(6):576-578.
[32]Arruda A P,G?khan S H.Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes[J].Cell Metabolism,2015,22(3):381-397.
[33]刘莹,王淑秋,李喆.2型糖尿病大鼠肾脏的钙稳态失衡、细胞色素C的变化与灵芝孢子粉的干预[J].中国老年学杂志,2009,29(3):267-269.
[34]吕俊华,杨文豪,沈文娟,等.绿茶多酚对D-半乳糖与Aβ25～35诱导Alzheimer病小鼠抗氧化能力和钙稳态的影响[J].中国老年学杂志,2006,26(8):1093-1095.
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