基于网络药理学研究丹参治疗帕金森病的作用机制
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摘要
目的:通过网络药理学技术预测并筛选丹参治疗帕金森病的活性成分及其潜在作用靶点,探讨丹参对帕金森病的多成分群-多靶点群-疾病的防治作用机制。方法:通过BATMAN-TCM预测并筛选丹参的活性成分及其作用靶点,利用Cytoscape软件构建丹参治疗帕金森病的成分和作用靶点网络,采用STRING数据库构建PPI网络,利用KOBAS数据库分析靶点的GO富集和KEGG信号通路。结果:筛选得到丹参的124个活性成分,预测涉及帕金森病的靶点11个,主要与ACHE、ADORA2A、AGTR1等靶点有关,其中10个靶点有相互作用关系,以P<0.05进行筛选,得到GO生物过程1 112条,其功能涉及多巴胺代谢、含儿茶酚的化合物代谢等过程。筛选得到34条信号通路,其中前20条KEGG通路为多巴胺能突触、神经活性配体-受体相互作用等相关通路。结论:揭示了丹参从多巴胺代谢过程、神经活性配体-受体相互作用等途径多成分-多靶点-多途径治疗帕金森病的作用机制,为靶向药物研发和阐明机制提供理论支撑。
AIM: To predict and screen the active constituents of Parkinson's disease and its potential targets by using network pharmacology techniques, and to explore the mechanism of prevention and treatment of Salvia miltiorrhiza on multi-component group-multi-target group-disease of Parkinson's disease. METHODS: BATMAN-TCM was used to predict and screen the active components and target of Salvia miltiorrhiza. The components and target network of Salvia miltiorrhiza in Parkinson's disease were constructed by using Cytoscape software. The PPI network was constructed by STRING database, and the target GO was analyzed by KOBAS database. Enrichment and KEGG signaling pathways. RESULTS:The 124 active components of Salvia miltiorrhiza were screened and 11 targets related to Parkinson's disease were predicted, which were mainly related to ACHE, ADORA2A, AGTR1 and other targets. Ten of them had interactions, and were screened at P<0.05. A total of 1 112 GO biological processes were obtained, the functions of which involved processes such as dopamine metabolism, catechol-containing compound metabolism. 34 signal pathways were screened, and the first 20 KEGG pathways were related to dopaminergic synapses and neuroactive ligand-receptor interactions. CONCLUSION:The mechanism of multi-component-multi-target-multi-pathway treatment of Parkinson's disease from dopamine metabolism process and neuroactive ligand-receptor interaction is revealed, which provides theoretical support for targeted drug development and clarification mechanism.
AIM: To predict and screen the active constituents of Parkinson's disease and its potential targets by using network pharmacology techniques, and to explore the mechanism of prevention and treatment of Salvia miltiorrhiza on multi-component group-multi-target group-disease of Parkinson's disease. METHODS: BATMAN-TCM was used to predict and screen the active components and target of Salvia miltiorrhiza. The components and target network of Salvia miltiorrhiza in Parkinson's disease were constructed by using Cytoscape software. The PPI network was constructed by STRING database, and the target GO was analyzed by KOBAS database. Enrichment and KEGG signaling pathways. RESULTS:The 124 active components of Salvia miltiorrhiza were screened and 11 targets related to Parkinson's disease were predicted, which were mainly related to ACHE, ADORA2A, AGTR1 and other targets. Ten of them had interactions, and were screened at P<0.05. A total of 1 112 GO biological processes were obtained, the functions of which involved processes such as dopamine metabolism, catechol-containing compound metabolism. 34 signal pathways were screened, and the first 20 KEGG pathways were related to dopaminergic synapses and neuroactive ligand-receptor interactions. CONCLUSION:The mechanism of multi-component-multi-target-multi-pathway treatment of Parkinson's disease from dopamine metabolism process and neuroactive ligand-receptor interaction is revealed, which provides theoretical support for targeted drug development and clarification mechanism.
引文
[1] Kalia LV,Lang AE.Parkinson's disease[J].Lancet,2015,386(9996) :896-912.
[2] 孙忠人,杨文明.神经病学[M].2 版.北京:人民卫生出版社,2016:102-110.
[3] Dorsey ER,Constantinescu R,Thompson JP,et al.Projected number of people with Parkinson disease in the most populous nations,2005 through 2030[J].Neurology,2007,68(5):384-386.
[4] Connolly BS,Lang AE.Pharmacological treatment of Parkinson disease:a review[J].Jama,2016,311(16):1670-1683.
[5] 黄少东,梁健芬,陈月桥,等.中药复方联合复方左旋多巴治疗帕金森病的临床研究进展[J].湖南中医药大学学报,2018,38(12):1471-1475.
[6] 赵荣博,黄小波,王倩,等.补肾解毒法治疗帕金森病轻度认知功能障碍的临床疗效观察[J].中华中医药杂志,2018,33(7):3172-3175.
[7] 韦一佛,陈路,张亚男,等.滋肾益髓方对帕金森病小鼠分子伴侣介导的自噬途径的影响[J].中华中医药杂志,2018 (9):106.
[8] 杨明会,李敏,窦永起,等.补肾活血颗粒对帕金森病患者脑内多巴胺水平的影响[J].中医杂志,2011,52(4):299-302.
[9] Wang JG,Bondy SC,Zhou L,et al.Protective effect of Tanshinone IIA against infarct size and increased HMGB1,NFκB,GFAP and apoptosis consequent to transient middle cerebral artery occlusion[J].Neurochemical Research,2014,39(2):295-304.
[10] 郑鸿燕,曾水林,李涛.丹参注射液促帕金森病移植神经元存活的实验研究[J].药学与临床研究,2004,12(2):1-3.
[11] Hopkins AL.Network pharmacology:the next paradigm in drug discovery[J].Nat Chem Biol,2008,4(11):682-690.
[12] 李泮霖,苏薇薇.网络药理学在中药研究中的最新应用进展[J].中草药,2016,47(16):2938-2942.
[13] Liu CX,Liu R,Fan HR,et al.Network Pharmacology bridges traditional application and modern development of traditional Chinese medicine[J].Chinese Herbal Medicines,2015,7(1):3-17.
[14] Liu Z,Guo F,Wang Y,et al.BATMAN-TCM:a bioinformatics analysis tool for molecular mechanism of traditional chinese medicine[J].Sci Rep,2016,6:21146.
[15] 张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
[16] 姚晓萌,曲庆洋,向冬生,等.多巴胺D1受体阻断剂SCH23390对帕金森病大鼠脚内核电活动的影响[J].中华神经医学杂志,2018,17(4):331-336.
[17] 丁家琦,陈晓莉,林家骥,等.敲低小鼠中脑神经元多巴胺D2受体使其生脂基因表达上调[J].细胞与分子免疫学杂志,2018,34(1):28-34.
[18] 潘天虹.多巴胺及多巴胺转运蛋白与帕金森病[J].中国细胞生物学学报,2001,23(3):166-168.
[19] Aflaki E,Borger DK,Moaven N,et al.A new glucocerebrosidase chaperone reduces α-synuclein and glycolipid levels in iPSC-derived dopaminergic neurons from patients with gaucher disease and Parkinsonism[J].J Neurosci,2016,36(28):7441-7452.
[2] 孙忠人,杨文明.神经病学[M].2 版.北京:人民卫生出版社,2016:102-110.
[3] Dorsey ER,Constantinescu R,Thompson JP,et al.Projected number of people with Parkinson disease in the most populous nations,2005 through 2030[J].Neurology,2007,68(5):384-386.
[4] Connolly BS,Lang AE.Pharmacological treatment of Parkinson disease:a review[J].Jama,2016,311(16):1670-1683.
[5] 黄少东,梁健芬,陈月桥,等.中药复方联合复方左旋多巴治疗帕金森病的临床研究进展[J].湖南中医药大学学报,2018,38(12):1471-1475.
[6] 赵荣博,黄小波,王倩,等.补肾解毒法治疗帕金森病轻度认知功能障碍的临床疗效观察[J].中华中医药杂志,2018,33(7):3172-3175.
[7] 韦一佛,陈路,张亚男,等.滋肾益髓方对帕金森病小鼠分子伴侣介导的自噬途径的影响[J].中华中医药杂志,2018 (9):106.
[8] 杨明会,李敏,窦永起,等.补肾活血颗粒对帕金森病患者脑内多巴胺水平的影响[J].中医杂志,2011,52(4):299-302.
[9] Wang JG,Bondy SC,Zhou L,et al.Protective effect of Tanshinone IIA against infarct size and increased HMGB1,NFκB,GFAP and apoptosis consequent to transient middle cerebral artery occlusion[J].Neurochemical Research,2014,39(2):295-304.
[10] 郑鸿燕,曾水林,李涛.丹参注射液促帕金森病移植神经元存活的实验研究[J].药学与临床研究,2004,12(2):1-3.
[11] Hopkins AL.Network pharmacology:the next paradigm in drug discovery[J].Nat Chem Biol,2008,4(11):682-690.
[12] 李泮霖,苏薇薇.网络药理学在中药研究中的最新应用进展[J].中草药,2016,47(16):2938-2942.
[13] Liu CX,Liu R,Fan HR,et al.Network Pharmacology bridges traditional application and modern development of traditional Chinese medicine[J].Chinese Herbal Medicines,2015,7(1):3-17.
[14] Liu Z,Guo F,Wang Y,et al.BATMAN-TCM:a bioinformatics analysis tool for molecular mechanism of traditional chinese medicine[J].Sci Rep,2016,6:21146.
[15] 张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
[16] 姚晓萌,曲庆洋,向冬生,等.多巴胺D1受体阻断剂SCH23390对帕金森病大鼠脚内核电活动的影响[J].中华神经医学杂志,2018,17(4):331-336.
[17] 丁家琦,陈晓莉,林家骥,等.敲低小鼠中脑神经元多巴胺D2受体使其生脂基因表达上调[J].细胞与分子免疫学杂志,2018,34(1):28-34.
[18] 潘天虹.多巴胺及多巴胺转运蛋白与帕金森病[J].中国细胞生物学学报,2001,23(3):166-168.
[19] Aflaki E,Borger DK,Moaven N,et al.A new glucocerebrosidase chaperone reduces α-synuclein and glycolipid levels in iPSC-derived dopaminergic neurons from patients with gaucher disease and Parkinsonism[J].J Neurosci,2016,36(28):7441-7452.