逍遥散“异病同治”抑郁症和糖尿病的网络药理学作用机制研究
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摘要
目的构建逍遥散单味药-成分-共有靶点网络、蛋白相互作用网络,探究逍遥散"异病同治"抑郁症和糖尿病的共同作用机制。方法通过TCMdatabase@Taiwan、TCMID、Batman-TCM数据库结合文献挖掘获取逍遥散的化学成分和作用靶点,结合CTD、TTD、Pharm GKB、OMIM、Gencards、Drugbank数据库获取逍遥散治疗抑郁症和糖尿病的作用靶点。采用Cytoscape软件绘制单味药-成分-共有靶点网络。采用Metascape工具对逍遥散治疗抑郁症和糖尿病的共有靶点进行GO生物过程分析、Reactome通路分析、KEGG通路分析、蛋白相互作用网络构建和模块分析。分别采用Bio GPS、Genecards分析通路关键靶点的组织分布和亚细胞分布,并采用Cytoscape软件绘制组织-靶点、亚细胞-靶点网络。采用Dis Ge NET数据库对通路关键靶点进行蛋白归属。结果逍遥散治疗糖尿病和抑郁症共病涉及免疫炎症反应,与G蛋白偶联受体、胰岛素及其受体、单胺类神经递质相关,通过调节环磷酸腺苷(c AMP)信号通路、钙信号通路、磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)信号通路等实现。结论逍遥散治疗抑郁症和糖尿病共病的作用机制涉及脑源性神经营养因子(BDNF)相关信号通路、G蛋白偶联受体、单胺类神经递质、胰岛素及其受体等调节过程,可为深入阐释逍遥散抗抑郁作用特点及其药理机制提供依据。
Objective In this paper, herb-component-common target network and protein interaction network were constructed to study the mechanism of Xiaoyao Powder in the treatment of depression and diabetes for exploring the common mechanism of Xiaoyao Powder in treating these two diseases. Methods TCM database@Taiwan, TCMID, Batman-TCM database and literature mining were used to obtain the components and targets of Xiaoyao Powder, combined with CTD, TTD, PharmGKB, OMIM, Gencards, and Drugbank databases to obtain the targets of Xiaoyao Powder in the treatment of depression and diabetes. The herb-component-common target network was constructed by Cytoscape software. The tool of Metascape was used to perform GO biological processes analysis, Reactome pathway analysis, KEGG pathway analysis, protein interaction networks construction and module analysis on the common targets of Xiaoyao Powder in the treatment of depression and diabetes. BioGPS database and Genecards database were used to analyze the tissue distribution and subcellular distribution of the hub targets, and the tissue-target network and subcellular-target network were constructed by Cytoscape. Protein class was performed on hub pathway targets by DisGeNET database. Results The results showed that the immune and inflammatory responses, G protein-coupled receptors, insulin and insulin receptors, and monoamine neurotransmitter were involved in the treatment of these two diseases by regulating cAMP signaling pathway, Calcium signaling pathway and PI3 K-Akt signaling pathway by Xiaoyao Powder. Conclusion It provides a direction for further research on Xiaoyao Powder's common mechanism in treating depression and diabetes. It suggests that the efficacy of Xiaoyao Powder in the treatment of depression and diabetes are mainly involved with the regulation of BDNF-related signaling pathways, the process of G protein-coupled receptors, monoamine neurotransmitter and the insulin and insulin receptors, which will benefit to the further investigation on the declaration of the characteristics of the pharmacological mechanism of Xiaoyao Powder.
Objective In this paper, herb-component-common target network and protein interaction network were constructed to study the mechanism of Xiaoyao Powder in the treatment of depression and diabetes for exploring the common mechanism of Xiaoyao Powder in treating these two diseases. Methods TCM database@Taiwan, TCMID, Batman-TCM database and literature mining were used to obtain the components and targets of Xiaoyao Powder, combined with CTD, TTD, PharmGKB, OMIM, Gencards, and Drugbank databases to obtain the targets of Xiaoyao Powder in the treatment of depression and diabetes. The herb-component-common target network was constructed by Cytoscape software. The tool of Metascape was used to perform GO biological processes analysis, Reactome pathway analysis, KEGG pathway analysis, protein interaction networks construction and module analysis on the common targets of Xiaoyao Powder in the treatment of depression and diabetes. BioGPS database and Genecards database were used to analyze the tissue distribution and subcellular distribution of the hub targets, and the tissue-target network and subcellular-target network were constructed by Cytoscape. Protein class was performed on hub pathway targets by DisGeNET database. Results The results showed that the immune and inflammatory responses, G protein-coupled receptors, insulin and insulin receptors, and monoamine neurotransmitter were involved in the treatment of these two diseases by regulating cAMP signaling pathway, Calcium signaling pathway and PI3 K-Akt signaling pathway by Xiaoyao Powder. Conclusion It provides a direction for further research on Xiaoyao Powder's common mechanism in treating depression and diabetes. It suggests that the efficacy of Xiaoyao Powder in the treatment of depression and diabetes are mainly involved with the regulation of BDNF-related signaling pathways, the process of G protein-coupled receptors, monoamine neurotransmitter and the insulin and insulin receptors, which will benefit to the further investigation on the declaration of the characteristics of the pharmacological mechanism of Xiaoyao Powder.
引文
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[18]刘洋,李艳,张海燕,等.抑郁症与糖尿病相关性研究进展[J].世界科学技术-中医药现代化,2017,19(8):1396-1400.
[19]李冬霞,陈文进,朱晓燕,等.糖尿病并发抑郁症的研究进展[J].医学信息,2018,31(14):20-23.
[20]李玉娟,罗和春,钱瑞琴,等.丹栀逍遥散对抑郁症患者神经免疫内分泌系统的影响[J].中国中西医结合杂志,2007,27(3):197-200.
[21]崔杰,郭秉荣,任艳玲,等.逍遥散不同提取部位对慢性轻度不可预知应激模型大鼠行为学及海马中单胺类神经递质的影响[J].中国医药工业杂志,2012,43(7):584-587.
[22]史碧云.复方柴归方超临界CO2萃取组分抗抑郁作用机制研究[D].太原:山西大学,2014.
[23]潘秋霞.肝郁脾虚证大鼠肝脏能量代谢紊乱的机制及逍遥散的调节作用[D].北京:北京中医药大学,2018.
[24]Dai B,Wu Q,Zeng C,et al.The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus(T2DM)rats with insulin resistance[J].J Ethnopharmacol,2016,192(11):382-389.
[25]Park B Y,Jeon J H,Go Y,et al.PDK4 deficiency suppresses hepatic glucagon signaling by decreasing cyclic AMP levels[J].Diabetes,2018,67(10):2054-2068.
[2]Ng M,Fleming T,Robinson M,et al.Global,regional,and national prevalence of overweight and obesity in children and adults during 1980-2013:A systematic analysis for the Global Burden of Disease Study 2013[J].Lancet,2014,384(9945):766-781.
[3]Hashim N A,Ariaratnam S,Salleh M R,et al.Depression and associated factors in patients with type 2 diabetes mellitus[J].East Asian Arch Psych,2016,26(2):77-82.
[4]何嘉莉,仇志坤.糖尿病合并抑郁症的研究及治疗进展[J].医学研究杂志,2016,45(3):7-9.
[5]刘媛,魏军平.中医药治疗糖尿病合并抑郁症临床研究概况[J].中医杂志,2014,55(10):889-892.
[6]Tian J,Peng G,Gao X,et al.Dynamic analysis of the endogenous metabolites in depressed patients treated with TCM formula Xiaoyaosan using urinary 1H NMR-based metabolomics[J].J Ethnopharmacol,2014,158:1-10.
[7]Zhu X,Xia O,Han W,et al.Xiao Yao San improves depressive-like behavior in rats through modulation ofβ-arrestin 2-mediated pathways in hippocampus[J].Evidence-Based Compl Altern Med,2014,doi:10.1155/2014/902516.
[8]周珺,张黎,席红领,等.逍遥散加减对糖尿病合并抑郁症治疗作用的Meta分析[J].中医学报,2017,32(10):1878-1882.
[9]Hopkins A L.Network pharmacology:The next paradigm in drug discovery[J].Nat Chem Biol,2008,4(11):682-690.
[10]Xu X,Zhang W,Huang C,et al.A novel chemometric method for the prediction of human oral bioavailability[J].Int J Mol Sci,2012,13(6):6964-6982.
[11]Yamanishi Y,Kotera M,Kanehisa M,et al.Drug-target interaction prediction from chemical,genomic and pharmacological data in an integrated framework[J].Bioinformatics,2010,26(12):i246-i254.
[12]吴丹,高耀,向欢,等.基于网络药理学的栀子豉汤抗抑郁作用机制研究[J].中草药,2018,49(7):1594-1602.
[13]李静,高丽,高耀,等.基于网络药理学的款冬花止咳化痰活性成分靶点探究[J].中草药,2018,49(1):179-187.
[14]Zhang Y Q,Mao X,Guo Q Y,et al.Network pharmacology-based approaches capture essence of Chinese herbal medicines[J].Chin Herb Med,2016,8(2):107-116.
[15]朱虹宇,李红品,高兴,等.交泰丸对糖尿病、抑郁和失眠症“异病同治”的网络药理学机制分析[J].世界科学技术-中医药现代化,2018,20(3):460-467.
[16]张雯,唐仕欢,张毅,等.基于整合药理学的越鞠丸“异病同治”研究[J].中国中药杂志,2018,43(7):1352-1359.
[17]蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究[J].世界科学技术-中医药现代化,2016,18(9):1507-1514.
[18]刘洋,李艳,张海燕,等.抑郁症与糖尿病相关性研究进展[J].世界科学技术-中医药现代化,2017,19(8):1396-1400.
[19]李冬霞,陈文进,朱晓燕,等.糖尿病并发抑郁症的研究进展[J].医学信息,2018,31(14):20-23.
[20]李玉娟,罗和春,钱瑞琴,等.丹栀逍遥散对抑郁症患者神经免疫内分泌系统的影响[J].中国中西医结合杂志,2007,27(3):197-200.
[21]崔杰,郭秉荣,任艳玲,等.逍遥散不同提取部位对慢性轻度不可预知应激模型大鼠行为学及海马中单胺类神经递质的影响[J].中国医药工业杂志,2012,43(7):584-587.
[22]史碧云.复方柴归方超临界CO2萃取组分抗抑郁作用机制研究[D].太原:山西大学,2014.
[23]潘秋霞.肝郁脾虚证大鼠肝脏能量代谢紊乱的机制及逍遥散的调节作用[D].北京:北京中医药大学,2018.
[24]Dai B,Wu Q,Zeng C,et al.The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus(T2DM)rats with insulin resistance[J].J Ethnopharmacol,2016,192(11):382-389.
[25]Park B Y,Jeon J H,Go Y,et al.PDK4 deficiency suppresses hepatic glucagon signaling by decreasing cyclic AMP levels[J].Diabetes,2018,67(10):2054-2068.