网络药理学探究二至丸防治阿尔茨海默病的物质基础与作用机制
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摘要
该研究采用网络药理学的方法,将阿尔茨海默病的关键靶点与二至丸化合物进行分子对接,通过Cytoscape 3.2.1软件,建立成分-靶点、靶点-信号通路网络模型进行网络分析,探讨二至丸防治阿尔茨海默病的物质基础与作用机制。模拟筛选出来的30个化合物与阿尔茨海默病关键靶点及靶点集中所在的Wnt,MAPK,PI3K-Akt-mTOR 3条信号通路均有很强的相互作用,其中有槲皮素、香叶醇、β-谷甾醇、橙花醇、圣草酚5个成分可通过文献验证,初步揭示了二至丸防治阿尔茨海默病的物质基础及其在3条信号通路上的作用机制。通过网络药理学方法发现,二至丸防治阿尔茨海默病的活性成分可能是槲皮素、香叶醇、β-谷甾醇、橙花醇、圣草酚,其作用机制可能与Wnt,MAPK,PI3K-Akt-mTOR 3条信号通路有关。
The present study is to explore the material basis and mechanism of Erzhi Wan the prevented Alzheimer's disease by using network pharmacology. The key target of Alzheimer' s disease was docked with the Erzhi Wan compounds,and the drugs-target combined with target-signal pathway network model was established by Cytoscape 3. 2. 1 software. Thirty compounds have a strong interaction with key target of Alzheimer's disease and three key pathways related with Wnt,MAPK and PI3 K-Akt-m TOR. There are 5 ingredients such as quercetin,geraniol,beta-sitosterol,nerol,eriodictyol that could be verified from literature. This result initially revealed the material basis for Erzhi Wan for Alzheimer's disease and the mechanism in terms of three signaling pathways. The network pharmacology method found that the active ingredients of Erzhi Wan for Alzheimer' s disease may be quercetin,geraniol,beta-sitosterol,nerol,and eriodictyol,and the mechanism may be related to three signal pathways including Wnt,MAPK,and PI3 K-Akt-m TOR.
The present study is to explore the material basis and mechanism of Erzhi Wan the prevented Alzheimer's disease by using network pharmacology. The key target of Alzheimer' s disease was docked with the Erzhi Wan compounds,and the drugs-target combined with target-signal pathway network model was established by Cytoscape 3. 2. 1 software. Thirty compounds have a strong interaction with key target of Alzheimer's disease and three key pathways related with Wnt,MAPK and PI3 K-Akt-m TOR. There are 5 ingredients such as quercetin,geraniol,beta-sitosterol,nerol,eriodictyol that could be verified from literature. This result initially revealed the material basis for Erzhi Wan for Alzheimer's disease and the mechanism in terms of three signaling pathways. The network pharmacology method found that the active ingredients of Erzhi Wan for Alzheimer' s disease may be quercetin,geraniol,beta-sitosterol,nerol,and eriodictyol,and the mechanism may be related to three signal pathways including Wnt,MAPK,and PI3 K-Akt-m TOR.
引文
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[22]代文博,曾亮.PI3K/Akt信号通路与阿尔茨海默病关系的研究进展[J].现代医药卫生,2014(10):1499.
[23]屈岭,顾蓓,张宏,等.中药筋脉通对糖尿病周围神经组织雪旺细胞自噬与凋亡的影响[C].北京:全国中西医结合内分泌代谢病学术大会暨中德代谢综合征高层论坛,2013.
[2]李林.中国阿尔茨海默病研究进展[J].中国药理学与毒理学杂志,2015,29(5):765.
[3]蔡秀江,黄美艳,丁安伟,等.二至丸考源及药理作用研究进展[J].中国实验方剂学杂志,2011,17(23):272.
[4]刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012(6):696.
[5]Liu C X,Liu R,Fan H R,et al.Network pharmacology bridges traditional application and modern development of traditional Chinese medicine[J].Chin Herb Med,2015,7(1):3.
[6]Ru J,Li P,Wang J,et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminformatics,2014,6(1):13
[7]陶晓倩,张新庄,李娜,等.网络药理学方法研究赤芍和黄柏干预阿尔茨海默病的作用机制[J].中草药,2015,46(11):1634.
[8]李冰涛.葛根芩连汤治疗2型糖尿病的配伍规律及作用机制研究[D].长沙:湖南中医药大学,2015.
[9]林卫东,陈超,梁生旺,等.人参皂苷改善胰岛素抵抗的网络药理学[J].中成药,2016,38(7):1455.
[10]Perry N S L,Houghton P J,Sampson J,et al.In vitro activity of S.lavandulaefolia(Spanish sage)relevant to treatment of Alzheimer's disease[J].J Pharm Pharmacol,2010,53(10):1347.
[11]Chuu C P,Kokontis J M,Hiipakka R A,et al.Modulation of liver X receptor signaling as novel therapy for prostate cancer[J].J Biomed Sci,2007,14(5):543.
[12]Howes M J,Houghton P J,Barlow D J,et al.Assessment of estrogenic activity in some common essential oil constituents[J].J Pharm Pharmacol,2010,54(11):1521.
[13]Cho J K,Ryu Y B,Curtis-Long M J,et al.Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits[J].Bioorg Med Chem,2012,20(15):4882.
[14]Zhang X,Jin H,Li Z,et al.Quercetin stabilizes apolipoprotein E and reduces brain Aβlevels in amyloid model mice[J].Neuropharmacology,2016,108:179.
[15]张雪玲,齐晓岚,单可人,等.阿尔茨海默病中β淀粉样蛋白与MAPK信号通路的关系[J].中国老年学,2011,31(13):2589.
[16]田允,蔡晶,陈旭征,等.补肾中药对帕金森病模型小鼠黑质-纹状体神经元的保护作用[J].中国老年学,2011,31(3):440.
[17]李杰.大黄素和槲皮素对LRRK2突变致PD果蝇的治疗作用探讨[D].苏州:苏州大学,2016.
[18]孔祥臣.新型化合物FLZ对热休克蛋白的诱导作用和对实验性帕金森氏病模型多巴胺系统保护作用及机制的研究[D].北京:北京协和医学院,2011.
[19]王薇,张海廷,王淑辉,等.阿尔茨海默病与Wnt信号通路及神经干细胞的关系[J].中国组织工程研究,2013,17(19):3566.
[20]De A.Wnt/Ca2+signaling pathway:a brief overview[J].Acta Biochim Biophys Sin,2011,43(10):745.
[21]吴婷,舒建洪.槲皮素对NRTI类药物引起的神经炎症的影响及其机制的初步探究[C].杭州:中国生物化学与分子生物学会2016年全国学术会议,2016.
[22]代文博,曾亮.PI3K/Akt信号通路与阿尔茨海默病关系的研究进展[J].现代医药卫生,2014(10):1499.
[23]屈岭,顾蓓,张宏,等.中药筋脉通对糖尿病周围神经组织雪旺细胞自噬与凋亡的影响[C].北京:全国中西医结合内分泌代谢病学术大会暨中德代谢综合征高层论坛,2013.