基于网络药理学方法分析金津玉液汤治疗2型糖尿病的机制及其治疗阿尔茨海默病的潜在性
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摘要
目的:应用网络药理学的方法分析中药验方金津玉液汤治疗2型糖尿病(T2DM)的作用机制及对阿尔茨海默病(AD)的治疗潜力。方法:应用在线数据库TCMSP,DrugBank及文本挖掘等方法筛选方剂中药材的活性成分、相关靶点和疾病。应用Cytoscape 3. 2. 1软件构建成分、靶点、疾病之间网络图,同时对靶点进行蛋白-蛋白相互作用分析、基因本体生物学过程富集分析(GO-BP)、KEGG富集分析等,联合GEO芯片分析评估金津玉液汤治疗T2DM的潜在作用机制和AD的可能性。结果:共筛选出169个成分,对应125个靶点。药材中的活性成分主要作用于炎症和胰岛素信号转导相关的靶点,例如,靶点蛋白PTGS2,AR,TNFα,INSR,GSK3B参与IKK/NF-κB信号通路,PI3K-AKt信号通路,胰岛素和胰岛素抵抗信号通路等,发挥治疗T2DM的作用。同时,这些成分可以直接或通过蛋白间相互作用间接作用于AD相关靶点,提示其具有治疗AD的潜在性。结论:金津玉液汤通过干预炎症的发生发展以及胰岛素信号转导相关过程发挥治疗2型糖尿病作用,同时可能对AD具有潜在的治疗作用。
Objective: To analyze the therapeutic mechanism of"Jinjin Yuye decoction"on type 2 diabetes mellitus(T2 DM) and its therapeutic potential for Alzheimer's disease(AD) by network pharmacology. Methods:The active ingredients of "Jinjin Yuye decoction",corresponding targets and diseases were collected through the on-line database TCMSP,Drug Bank and literature. Meanwhile,the compound-target-disease network was constructed by Cytoscape 3. 2. 1 software. Protein-protein interaction analysis,GO-BP and KEGG enrichment analysis were performed based on the target sites,and GEO chip analysis was also evaluated to find out the potential mechanism of "Jinjin Yuye decoction " in the treatment of T2 DM and the therapeutic potential for Alzheimer's disease.Results: 169 ingredients and 125 targets were selected. The active compounds are mainly related to the targets of inflammatory and insulin signal transduction,such as PTGS2,AR,TNF alpha,INSR and PTPN1. These targets are mainly involved GSK3 B,in IKK/NF-kappa B,PI3 K-Akt,Insulin and Insulin resistance signal transduction process and play a role in the treatment of type 2 diabetes. Meanwhile these components can directly affect the target of Alzheimer's disease,or indirectly play a role in the treatment of Alzheimer's disease through protein-protein interaction. It indicates that these components have the potential to treat Alzheimer's disease. Conclusion: "JinjinYuye decoction"treatments the type 2 diabetes by intervening the signal transduction of insulin and inflammation process,and it may also play a therapeutic role in Alzheimer's disease.
Objective: To analyze the therapeutic mechanism of"Jinjin Yuye decoction"on type 2 diabetes mellitus(T2 DM) and its therapeutic potential for Alzheimer's disease(AD) by network pharmacology. Methods:The active ingredients of "Jinjin Yuye decoction",corresponding targets and diseases were collected through the on-line database TCMSP,Drug Bank and literature. Meanwhile,the compound-target-disease network was constructed by Cytoscape 3. 2. 1 software. Protein-protein interaction analysis,GO-BP and KEGG enrichment analysis were performed based on the target sites,and GEO chip analysis was also evaluated to find out the potential mechanism of "Jinjin Yuye decoction " in the treatment of T2 DM and the therapeutic potential for Alzheimer's disease.Results: 169 ingredients and 125 targets were selected. The active compounds are mainly related to the targets of inflammatory and insulin signal transduction,such as PTGS2,AR,TNF alpha,INSR and PTPN1. These targets are mainly involved GSK3 B,in IKK/NF-kappa B,PI3 K-Akt,Insulin and Insulin resistance signal transduction process and play a role in the treatment of type 2 diabetes. Meanwhile these components can directly affect the target of Alzheimer's disease,or indirectly play a role in the treatment of Alzheimer's disease through protein-protein interaction. It indicates that these components have the potential to treat Alzheimer's disease. Conclusion: "JinjinYuye decoction"treatments the type 2 diabetes by intervening the signal transduction of insulin and inflammation process,and it may also play a therapeutic role in Alzheimer's disease.
引文
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[18]赖琼,张海燕,杨启悦,等.从“治脑病”角度探讨糖尿病及其阿尔茨海默病的防治[J].中国新药杂志,2017,26(5):509-513.
[19]余美霞,刘迅,杜柳涛,等.经典途径IKKα和IKKβ在胰岛素抵抗和2型糖尿病中的作用机制及药物治疗[J].中国新药杂志,2017,26(5):535-541.
[20]李慧.治疗阿尔茨海默病药物的临床研究进展[J].中国新药杂志,2017,26(6):648-655.
[2] STEEN E,TERRY BM,RIVERA EJ,et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease——is this type 3 diabetes?[J]. J Alzheimers Dis,2005,7(1):63-80.
[3]邓海清.刘仲生金津玉液汤治疗糖尿病63例临床观察[J].江西中医药,2001,32(1):7.
[4]黄国荣.金津玉液汤治疗2型糖尿病临床观察[J].湖北中医杂志,2004,26(12):29.
[5] DENNIS G,SHERMAN BT,HOSACK DA,et al. DAVID:database for annotation,visualization,and integrated discovery[J].Genome Biology,2003,4(5):3.
[6] KHAN S,ZHANG D,ZHANG Y,et al. Wogonin attenuates diabetic cardiomyopathy through its anti-inflammatory and anti-oxidative properties[J]. Mol Cell Endocrinol,2016,428:101-108.
[7] KU SK,BAE JS. Baicalin,baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo[J].Bmb Reports,2015,48(9):519-524.
[8] XU N,ZHANG L,DONG J,et al. Low-dose diet supplement of a natural flavonoid,luteolin,ameliorates diet-induced obesity and insulin resistance in mice[J]. Mol Nutr Food Res,2014,58(6):1258-1268.
[9] YOKOKAWA T,SATO K,IWANAKA N,et al. Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1αexpression in C2C12 myotubes[J]. Biochem Bioph Res Co,2015,463(1-2):42-47.
[10] SATO K,FUJITA S,IEMITSU M. Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats.[J]. J Steroid Biochem Mol Biol,2014,143(9):152-159.
[11] BOSCO D,FAVA A,PLASTINO M,et al. Possible implications of in-sulin resistance and glucose metabolism in Alzheimer's disease pathogenesis[J]. J Cell Mol Med,2011,15(9):1807-1821.
[12] TONG Q,HOTAMISLIGIL GS. Molecular mechanisms of adipoeyte differentiation[J]. Rev Endocr Metab Dis,2001,2(4):349-355.
[13]张强,高天舒.健脾和胃法控制二甲双胍胃肠道副作用[J].实用中医内科杂志,2013,27(10):39-40.
[14] LI S,ZHANG B. Traditional Chinese medicine network pharmacology:theory,methodology and application.[J]. Chin J Nat Med,2013,11(2):110.
[15] LIN L. Commonality between diabetes and Alzheimer's disease and a new strategy for the therapy[J]. Clin Med Pathol,2008,1:83-91.
[16] NASRALLAH R,HASSOUNEH R,HBERT RL. PGE2,kidney disease,and cardiovascular risk:beyond hypertension and diabetes[J]. J Am Soc Nephrol,2016,27(3):666-676.
[17]吴亚柳,常晓彤.胰岛素信号通路、炎症信号通路与泛素-蛋白酶体系统的交互作用[J].中国生物化学与分子生物学报,2016,32(11):1177-1184.
[18]赖琼,张海燕,杨启悦,等.从“治脑病”角度探讨糖尿病及其阿尔茨海默病的防治[J].中国新药杂志,2017,26(5):509-513.
[19]余美霞,刘迅,杜柳涛,等.经典途径IKKα和IKKβ在胰岛素抵抗和2型糖尿病中的作用机制及药物治疗[J].中国新药杂志,2017,26(5):535-541.
[20]李慧.治疗阿尔茨海默病药物的临床研究进展[J].中国新药杂志,2017,26(6):648-655.