基于分子对接技术石菖蒲中抗抑郁活性成分的筛选
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摘要
目的用分子对接技术筛选石菖蒲中抗抑郁的活性成分。方法通过检索传统中药药理数据库(TCMSP)得到石菖蒲的所有化学成分,结合口服生物利用度,筛选出65个候选化合物,以单胺氧化酶A、多巴胺转运体、5-羟色胺转运体和组胺H1受体为抗抑郁药物作用靶点,采用AutoDock Vina分子对接软件,探索候选化合物与上述靶点的亲和力以及结合方式。结果石菖蒲中有18个化合物能与上述4个靶点结合,其中有4个化合物能与4个靶点发生结合,有3个化合物能与2个靶点发生结合,其余11种化合物能与1个靶点发生相互作用。结论分子对接技术可以为石菖蒲抗抑郁活性成分的确定和分子机制研究提供参考,为发现新型抗抑郁中药单体和先导化合物提供研究方向。
Objective To screen the anti-depressant active ingredients in Acori Tatarinowii Rhizoma by molecular docking technique.Methods All the chemical constituents of Acori Tatarinowii Rhizoma were obtained by Traditional Chinese Medicine Pharmacology Database(TCMSP). Combined with oral bioavailability, 65 candidate compounds were obtained. The studied anti-depressant targets included monoamine oxidase A, dopamine transporter, serotonin transporter, and histamine H1 receptor. AutoDock Vina was used to explore the affinity and binding modes of the candidate compounds with the above targets. Results There were 18 compounds from Acori Tatarinowii Rhizoma that could bind to the above four targets. Among them, four compounds could bind to four targets, three compounds could bind to two targets, and the other 11 compounds could interact with one target. Conclusion Molecular docking technology can be used to investigate the molecular mechanism of Acori Tatarinowii Rhizoma and determine the active ingredients,which provides an alternative method for the discovery of novel anti-depressants and lead compounds from Chinese herbal medicines.
Objective To screen the anti-depressant active ingredients in Acori Tatarinowii Rhizoma by molecular docking technique.Methods All the chemical constituents of Acori Tatarinowii Rhizoma were obtained by Traditional Chinese Medicine Pharmacology Database(TCMSP). Combined with oral bioavailability, 65 candidate compounds were obtained. The studied anti-depressant targets included monoamine oxidase A, dopamine transporter, serotonin transporter, and histamine H1 receptor. AutoDock Vina was used to explore the affinity and binding modes of the candidate compounds with the above targets. Results There were 18 compounds from Acori Tatarinowii Rhizoma that could bind to the above four targets. Among them, four compounds could bind to four targets, three compounds could bind to two targets, and the other 11 compounds could interact with one target. Conclusion Molecular docking technology can be used to investigate the molecular mechanism of Acori Tatarinowii Rhizoma and determine the active ingredients,which provides an alternative method for the discovery of novel anti-depressants and lead compounds from Chinese herbal medicines.
引文
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[2]王睿,费洪新,李晓明,等.石菖蒲的化学成分及药理作用研究进展[J].中华中医药学刊,2013,31(7):1606-1610.
[3]冯波,靖慧军,郭敏娟,等.石菖蒲挥发油和水煎液的抗焦虑作用[J].中国实验方剂学杂志,2014,20(9):207-210.
[4]Ru J,Li P,Wang J,et al.TCMSP:A database of systems pharmacology for drug discovery from herbalmedicines[J].J Cheminform,2014,6(1):13-19.
[5]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(12):6964-6982.
[6]Gammoh O,Mayyas F,Darwish E F.Chlorpheniramine and escitalopram:Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety[J].Biomed Reports,2017,6(6):675-680.
[7]Erol I,Aksoydan B,Kantarcioglu I,et al.Identification of novel serotonin reuptake inhibitors targeting central and allosteric binding sites:A virtual screening and molecular dynamics simulations study[J].J Mol Graph Model,2017,74(5):193-202.
[8]Talbot J N,Geffert L M,Jorvig J E,et al.Rapid and sustained antidepressant properties of an NMDAantagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening[J].Pharmacol Biochem Behav,2016,150/151(10):22-30.
[9]Trott O,Olson A J.Auto Dock Vina:Improving the speed and accuracy of docking with a new scoring function,efficient optimization,and multithreading[J].J Comput Chem,2010,31(2):455-461.
[10]Goddard T D,Huang C C,Ferrin T E.Visualizing density maps with UCSF Chimera[J].J Struct Biol,2007,157(1):281-287.
[11]Son S Y,Ma J,Kondou Y,et al.Structure of human monoamine oxidase A at 2.2-A resolution:The control of opening the entry for substrates/inhibitors[J].Proceed Nat Acad Sci,2008,105(15):5739-5744.
[12]Penmatsa A,Wang K H,Gouaux E.X-ray structure of dopamine transporter elucidates antidepressant mechanism[J].Nature,2013,503(7474):85-90.
[13]Shimamura T,Shiroishi M,Weyand S,et al.Structure of the human histamine H1 receptor complex with doxepin[J].Nature,2011,475(7354):65-70.
[14]Coleman J A,Green E M,Gouaux E.X-ray structures and mechanism of the human serotonin transporter[J].Nature,2016,532(7599):334-349.
[15]梁子亮,张旭毅,欧阳璞心,等.抗高原反应中药红景天化学成分的潜在靶标研究[J].中华灾害救援医学,2017,5(4):186-190.
[16]Lill M A,Danielson M L.Computer-aided drug design platform using PyMOL[J].J Computer-Aided Mol Design,2011,25(1):13-19.
[17]Laskowski R A,Swindells M B.LigPlot+:Multiple ligand-protein interaction diagrams for drug discovery[J].J Chem Inform Model,2011,51(10):2778-2786.
[18]张忠廉,罗祖良,石宏武,等.植物药活性成分环阿屯醇药理、生理活性及其研究展望[J].中国中药杂志,2017,42(3):433-437.
[19]Upadhyay S,Tripathi A C,Paliwal S,et al.Facile One-Pot synthesis methodology for nitrogen-containing heterocyclic derivatives of 3 5-disubstituted 45-dihydro-1H-pyrazole,their biological evaluation and molecular docking studies[J].Pharm Chem J,2017,51(7):564-575.
[20]Penmatsa A,Wang K H,Gouaux E.X-ray structure of dopamine transporter elucidates antidepressant mechanism[J].Nature,2013,503(7474):85-90.
[21]Heifetz A,Chudyk E I,Gleave L,et al.The fragment molecular orbital method reveals new insight into the chemical nature of GPCR-ligand interactions[J].J Chem Inform Model,2015,56(1):159-172.
[22]Henry L K,Field J R,Adkins E M,et al.Tyr-95 and Ile-172 in fransmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants[J].J Biol Chem,2006,281(4):2012-2023.
[23]卢成淑,冯宁,南国,等.石菖蒲及其活性成分防治阿尔茨海默病的研究进展[J].中草药,2016,47(7):1236-1242.
[24]王联生,潘菊华.石菖蒲治疗抑郁症的研究进展[J].环球中医药,2017,10(4):509-512.
[25]高志影,张春,董海影,等.石菖蒲有效成分对抑郁模型大鼠海马神经元的保护作用[J].中国老年学杂志,2014,34(4):1000-1002.
[26]陈蕾.黄酮类化合物的抗抑郁作用研究[J].国际精神病学杂志,2012,39(1):30-32.
[27]王佳,陈岳明,高力舒,等.山柰酚对乳腺癌抑郁模型大鼠的抗抑郁作用研究[J].中国现代应用药学,2016,33(3):277-280.
[28]孔令雷,胡金凤,陈乃宏.香豆素类化合物药理和毒理作用的研究进展[J].中国药理学通报,2012,28(2):165-168.
[29]吴全娥,高彦宇,李在斯,等.尖叶假龙胆与石菖蒲配伍抗抑郁的作用机理研究[J].中医药信息,2016,33(3):72-74.
[30]周天,李辉,凃中一,等.石菖蒲不同极性部位对抑郁模型小鼠抗抑郁效应及其机制[J].医药导报,2016,35(4):327-330.
[31]刘梅,周海松,许锦文,等.藜欢解郁胶囊的抗抑郁作用[J].中成药,2016,38(6):1383-1387.