Thermal Shift高通量筛选法快速筛选覆盆子中雌激素样活性化合物
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摘要
[目的]从覆盆子中筛选具有雌激素样活性的化合物。[方法]基于配体=受体理论,以人源雌激素受体亚型的配体结合域(hERα-LBD、hERβ-LBD)为靶点,以17β-雌二醇(E_2)为阳性对照,采用Thermal Shift高通量筛选方法筛选覆盆子中具有雌激素样活性的化合物。[结果]山柰酚明显提高雌激素受体配体结合域的(hERα-LBD、hERβ-LBD)热稳定性。[结论]山柰酚能与hERα-LBD和h ERβ-LBD结合,具有雌激素样活性。
[Objective] To screen estrogen-like active compounds from Rubus chingii Hu. [Methods] The subtypes of human estrogen receptor ligand binding domain(hERα-LBD and hERβ-LBD) were chosen as targets and E_2 was set as positive control to screen compounds with estrogen-like activity from Rubus chingii Hu by using Thermal Shift high throughput method based on the ligandreceptor theory. [Results] Kaempferol can significantly increase the thermal stability of hERα-LBD and hERβ-LBD. [Conclusion]Kaempferol have an estrogen-like activity, which can bind to hERα-LBD and hERβ-LBD.
[Objective] To screen estrogen-like active compounds from Rubus chingii Hu. [Methods] The subtypes of human estrogen receptor ligand binding domain(hERα-LBD and hERβ-LBD) were chosen as targets and E_2 was set as positive control to screen compounds with estrogen-like activity from Rubus chingii Hu by using Thermal Shift high throughput method based on the ligandreceptor theory. [Results] Kaempferol can significantly increase the thermal stability of hERα-LBD and hERβ-LBD. [Conclusion]Kaempferol have an estrogen-like activity, which can bind to hERα-LBD and hERβ-LBD.
引文
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[24]陈育华,周克元,袁汉尧.山柰酚药效的研究进展[J].广东医学,2010,31(8):1064-1066.
[2]杜龙飞,李洁,杨龙,等.覆盆子的化学成分研究[J].天然产物研究与开发,2014,26(12):1957-1960.
[3]朱俊萍,范东瀛.Thermal Shift Assays在重组森林脑炎病毒丝氨酸蛋白酶纯化中的应用[J].中国生物工程杂志,2009,29(11):53-59.
[4]De CL,Wang X,Spyrou JA,et al.More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules[J].Nat Struct Mol Biol,2014,21(3):282-288.
[5]Zubriene A,Matuliene J,Baranauskiene L,et al.Measurement of nanomolar dissociation constants by titration calorimetry and thermal shift assay-radicicol binding to Hsp90 and ethoxzolamide binding to CAII[J].Int J Mol Sci,2009,10(6):2662-2680.
[6]Fu X,Wang Z,Li L,et al.Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches[J].Sci Rep,2016(6):29680.
[7]龚剑秋,梁文清.覆盆子抗骨质疏松化学组成及抗骨质疏松活性成分研究[J].中华中医药学刊,2016,34(3):657-659.
[8]王俊玲,黄思敏,梁启瑶,等.雌激素的来源及其在骨代谢中的作用[J].中国骨质疏松杂志,2015,21(6):729-732.
[9]Lagari VS,Levis S.Phytoestrogens in the prevention of postmenopausal bone loss[J].Clin Densitom,2013,16(4):445-449.
[10]程科军.Ⅰ.覆盆子活性成分研究Ⅱ.金雀根中二苯乙烯类成分的稳定性研究[D].上海:复旦大学,2008.
[11]Takeshi U.Pharmaceutical prospects of phytoestrogens[J].Endocr J,2006,53(1):7.
[12]袁婷婷,张乃丹,何勇静,等.天然药物中植物雌激素样化学成分的研究进展[J].中国中药杂志,2014,39(23):4526-4531.
[13]黄颖,周艳华,崔海峰,等.雌激素调节作用机制研究进展[J].中国医药导报,2010,7(5):7-8,11.
[14]孟庆书,何平,朱晓燕,等.植物雌激素的作用机制[J].生命的化学,2007,27(2):141-143.
[15]赵晓民,徐小明.雌激素受体及其作用机制[J].西北农林科技大学学报(自然科学版),2004,32(12):154-158.
[16]Anderson GL,Limacher M,Assaf A R,et al.Effects of conjugated equine estrogen in postmenopausal women with hysterectomy:the Women's Health Initiative randomized controlled trial[J].JAMA-The Journal of the American Medical Association,2004,291(14):1701-1712.
[17]Rossouw JE,Anderson GL,Prentice RL,et al.Risks and benefits oestrogen plus progestin in healthy postmenopausal women:principal results From the Women's Health Initiative randomized controlled trial[J].JAMA-The Journal of the American Medical Association,2002,288(3):321-333.
[18]Branca F,Lorenzetti S.Health effects of phytoestrogens[J].Forum Nutr,2005,57(57):100-111.
[19]Soto AM,Sonnenschein C,Chung KL,et al.The E-screen assay as a tool to identify estrogens:an update on estrogenic environmental pollutants[J].Environ Health Perspect,1995,103(7):113.
[20]Mueller SO.Overview of in vitro tools to assess the estrogenic and antiestrogenic activity of phytoestrogens[J].Chromatography B,2002,777(1-2):155.
[21]Cos P,De Bruyne T,Apers S,et al.Phytoestrogens:recent developments[J].Planta Medica,2003,69(7):589-599.
[22]Strauss L,Santti R,Saarinen N,et al.Dietary phytoestrogens and their role in hormonally dependent disease[J].Toxicology Letters,1998,102-103(102/103):349-354.
[23]Cassidy A,Hanley B,Lamuela-Raventos RM.Isoflavones,lignans and stilbenesorigins,metabolism and potential importance to human health[J].Journal of the Science of Food and Agriculture,2000,80(7):1044-1062.
[24]陈育华,周克元,袁汉尧.山柰酚药效的研究进展[J].广东医学,2010,31(8):1064-1066.