基于亲和超滤技术的天然活性物质筛选方法

doi:10.3969/j.issn.1000-1565.2021.05.008

摘要/Abstract

摘要： 药效物质与药物靶标的相互作用是其生物活性的基础,利用药物靶标亲和选择性“钩钓”其特异性配体,可以实现复杂提取物中天然活性物质分析的“精准制导”.亲和超滤是一种以上述原理为基础,将亲和捕获与超滤分离相结合以实现化合物高通量筛选的技术,具有快速、简单、高效等特点,常与液质联用等分析技术联合使用,克服了天然活性物质筛选研究面临的诸多问题,近年来被广泛应用于天然活性物质的快速靶向筛选.本文从亲和超滤技术本身的原理、影响因素及与其他分析技术的联用情况等方面,详细综述了亲和超滤技术的特点和应用现状,以期为构建天然活性物质的快速筛选策略提供科学思路和依据.

关键词: 亲和超滤, 天然活性物质, 筛选方法

Abstract: The interaction between medicinal substance and drug target is the basis of biological activity- DOI:10.3969/j.issn.1000-1565.2021.05.008基于亲和超滤技术的天然活性物质筛选方法王志强¹,韩晔红²,闫宏远^1,2(1.河北大学公共卫生学院,河北省公共卫生安全重点实验室,河北保定 071002;2.河北大学药学院,药物化学与分子诊断教育部重点实验室,河北保定 071002)闫宏远工学博士,河北大学教授,博士生导师.河北省杰出青年基金获得者,河北省“三三三人才工程”人选,河北省高校百名优秀创新人才;现任中国医检整合联盟常务理事、河北省预防医学会副理事长、河北省检验检疫学会副理事长、河北省分析仪器技术学会副理事长、河北省健康学会常务理事、《中华疾病控制杂志》常务编委、《医学理论与实践》编委、河北省公共卫生安全重点实验室主任.近年来主持国家自然科学基金面上项目、河北省自然科学基金重点项目等10余项,在国际学术期刊上发表研究论文50余篇;授权国家发明专利6项;2016年获河北省自然科学奖三等奖,2019年获河北省科技进步奖二等奖.2020年入选“中国高被引学者”和斯坦福大学发布的“2020全球前2%顶尖科学家”榜单.摘要:药效物质与药物靶标的相互作用是其生物活性的基础,利用药物靶标亲和选择性“钩钓”其特异性配体,可以实现复杂提取物中天然活性物质分析的“精准制导”.亲和超滤是一种以上述原理为基础,将亲和捕获与超滤分离相结合以实现化合物高通量筛选的技术,具有快速、简单、高效等特点,常与液质联用等分析技术联合使用,克服了天然活性物质筛选研究面临的诸多问题,近年来被广泛应用于天然活性物质的快速靶向筛选.本文从亲和超滤技术本身的原理、影响因素及与其他分析技术的联用情况等方面,详细综述了亲和超滤技术的特点和应用现状,以期为构建天然活性物质的快速筛选策略提供科学思路和依据.关键词:亲和超滤;天然活性物质;筛选方法中图分类号:R917;R93 文献标志码:A 文章编号:1000-1565(2021)05-0511-17Screening methods of natural bioactive compounds based on the affinity ultrafiltration techniquesWANG Zhiqiang¹, HAN Yehong², YAN Hongyuan^1,2(1. Key Laboratory of Public Health Safety of Hebei Province, College of Public Health, Hebei University, Baoding 071002,China;2. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Pharmaceutical Sciences, Hebei University, Baoding 071002,China)Abstract: The interaction between medicinal substance and drug target is the basis of biological activity- 收稿日期:2021-06-08 基金项目:国家自然科学基金资助项目(81803401;82073605);河北省自然科学基金资助项目(H2019201186) 第一作者:王志强(1989—),男,黑龙江鹤岗人,河北大学副教授,主要从事天然活性物质筛选研究.E-mail:wangzq2017@hbu.edu.cn 通信作者:闫宏远(1975—),男,河北高阳人,河北大学教授,博士生导师,主要从事药物分离分析技术研究.E-mail:yanhy@hbu.edu.cn第5期王志强等:基于亲和超滤技术的天然活性物质筛选方法for the medicinal substance, and “precise guidance” of natural bioactive compounds from complex extracts can be achieved by the selective affinity of drug target, just like “fishing”. Affinity ultrafiltration is a technology that combines affinity capture and ultrafiltration separation for high-throughput screening of bioactive compounds based on the above principles, which is often coupled with liquid chromatography-mass spectrometry, overcoming lots of problems in discovering bioactive natural products. This paper reviewed in detail the characteristics and application status of affinity ultrafiltration technology, influencing factors, and the combination with other analytical technologies, in order to provide scientific ideas and basis for the construction of rapid screening strategies for natural active substances.

Key words: affinity ultrafiltration, natural bioactive compounds, screening methods

中图分类号:

R917
R93

王志强,韩晔红,闫宏远. 基于亲和超滤技术的天然活性物质筛选方法[J]. 河北大学学报(自然科学版), 2021, 41(5): 511-527.

WANG Zhiqiang, HAN Yehong, YAN Hongyuan. Screening methods of natural bioactive compounds based on the affinity ultrafiltration techniques[J]. Journal of Hebei University(Natural Science Edition), 2021, 41(5): 511-527.

参考文献

[1] NEWMAN D J, CRAGG G M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019[J]. J Nat Prod, 2020, 83(3): 770-803. DOI: 10.1021/acs.jnatprod.9b01285.
[2] VAN BREEMEN R B, HUANG C R, NIKOLIC D, et al. Pulsed ultrafiltration mass spectrometry: a new method for screening combinatorial libraries[J]. Anal Chem,1997, 69: 2159-2164. DOI: 10.1021/ac970132j.
[3] WEI H, ZHANG X, TIAN X, et al. Pharmaceutical applications of affinity-ultrafiltration mass spectrometry: recent advances and future prospects[J]. J Pharm Biomed Anal, 2016, 131: 444-453. DOI: 10.1016/j.jpba.2016.09.021.
[4] WU B, SONG H P, ZHOU X, et al. Screening of minor bioactive compounds from herbal medicines by in silico docking and the trace peak exposure methods[J]. J Chromatogr A, 2016, 1436: 91-99. DOI: 10.1016/j.chroma.2016.01.062.
[5] ZHANG G, GUO X H, WANG S S, et al. Screening and identification of natural ligands of tyrosinase from Pueraria lobata Ohwi by a combination of ultrafiltration and LC-MS[J]. Anal Methods, 2017, 9: 4858-4862. DOI: 10.1039/C7AY00851A.
[6] ZUO G, WANG Z, GUILLEN QUISPE Y N, et al. Target guided isolation of potential tyrosinase inhibitors from Otholobium pubescens(Poir.)J.W. Grimes by ultrafiltration, high-speed countercurrent chromatography and preparative HPLC[J]. Ind Crop Prod, 2019, 134: 195-205. DOI: 10.1016/j.indcrop.2019.03.045.
[7] MAYR F, STURM S, GANZERA M, et al. Mushroom tyrosinase-based enzyme inhibition assays are not suitable for bioactivity-guided fractionation of extracts[J]. J Nat Prod, 2019, 82(1): 136-147. DOI: 10.1021/acs.jnatprod.8b00847.
[8] WANG Z, HWANG S H, HUANG B, et al. Identification of tyrosinase specific inhibitors from Xanthium strumarium fruit extract using ultrafiltration-high performance liquid chromatography[J]. J Chromatogr B, 2015, 1002: 319-328. DOI: 10.1016/j.jchromb.2015.08.030.
[9] LIU H, ZHU Y, WANG T, et al. Enzyme-site blocking combined with optimization of molecular docking for efficient discovery of potential tyrosinase specific inhibitors from Puerariae lobatae Radix[J]. Molecules, 2018, 23(10): 2612. DOI: 10.3390/molecules23102612.
[10] WANG Z, KWON S H, HWANG S H, et al. Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract[J]. J Chromatogr B, 2017, 1048: 30-37. DOI: 10.1016/j.jchromb.2017.02.001.
[11] SHIBATA S, ZHANG Z, KOROTKOV K V, et al. Screening a fragment cocktail library using ultrafiltration[J]. Anal Bioanal Chem, 2011, 401(5): 1585-1591. DOI: 10.1007/s00216-011-5225-7.
[12] QIN S, REN Y, FU X, et al. Multiple ligand detection and affinity measurement by ultrafiltration and mass spectrometry analysis applied to fragment mixture screening[J]. Anal Chim Acta, 2015, 886: 98-106. DOI: 10.1016/j.aca.2015.06.017.
[13] WANG Z, ZUO G, HWANG S H, et al. Affinity measurement of ligands in Perilla frutescens extract towards alpha-glucosidase using affinity-based ultrafiltration-high-performance liquid chromatography[J]. J Chromatogr B, 2019, 1125: 121725. DOI: 10.1016/j.jchromb.2019.121725.
[14] SONG H P, WANG H, LIANG J X, et al. Integration of multiple analytical and computational tools for the discovery of high-potency enzyme inhibitors from herbal medicines[J]. Chem Med Chem, 2016, 11(23): 2588-2597. DOI: 10.1002/cmdc.201600489.
[15] WANG Z, HWANG S H, LIM S S. Comprehensive profiling of minor tyrosinase inhibitors from Gastrodia elata using an off-line hyphenation of ultrafiltration, high-speed countercurrent chromatography, and high-performance liquid chromatography[J]. J Chromatogr A, 2017, 1529: 63-71. DOI: 10.1016/j.chroma.2017.11.008.
[16] ZHAO H, LAI C, ZHANG M, et al. An improved 2D-HPLC-UF-ESI-TOF/MS approach for enrichment and comprehensive characterization of minor neuraminidase inhibitors from Flos Lonicerae Japonicae[J]. J Pharm Biomed Anal, 2019, 175: 112758. DOI: 10.1016/j.jpba.2019.07.006.
[17] WHITLAM J B, BROWN K F. Ultrafiltration in serum protein binding determinations[J]. J Pharm Sci, 1981, 70: 146-150. DOI: 10.1002/jps.2600700208.
[18] WIEBOLDT R, ZWEIGENBAUM J, HENION J. Immunoaffinity ultrafiltration with ion spray HPLC/MS for screening small-molecule libraries[J]. Anal Chem, 1997, 69: 1683-1691. DOI: 10.1021/ac9610265.
[19] 徐晨,刘舒,刘志强,等.离心超滤质谱法筛选中药复方二妙丸中黄嘌呤氧化酶抑制剂[J].高等学校化学学报, 2014, 35(8): 1640-1645.DOI:10.7503/cjcu20140419.
[20] 马丽娜,章从恩,鄢丹,等.超滤质谱技术筛选板蓝根中抗流感病毒的活性成分[J].中国中药杂志, 2014, 39(5): 812-816.DOI:10.4268/cjcmm.20140511.
[21] ZHONG H, ABDYKKAH, ZHANG Y, et al. Exploring the potential of novel xanthine oxidase inhibitory peptide(ACECD)derived from Skipjack tuna hydrolysates using affinity-ultrafiltration coupled with HPLC-MALDI-TOF/TOF-MS[J]. Food Chem, 2021, 347: 129068. DOI: 10.1016/j.foodchem.2021.129068.
[22] IJZERMAN A P, GUO D. Drug-target association kinetics in drug discovery[J]. Trends Biochem Sci, 2019, 44(10): 861-871. DOI: 10.1016/j.tibs.2019.04.004.
[23] GASHAW I, ELLINGHAUS P, SOMMER A, et al. What makes a good drug target[J]. Drug Discov Today, 2011, 16: 1037-1043. DOI: 10.1016/j.drudis.2011.09.007.
[24] WANG Z, HWANG S H, ZUO G, et al. An in vitro affinity-based method for studying herb-drug interactions for direct identification of cytochrome P450 1A2, 3A4, and 2C9 specific ligands from herbal extracts using ultrafiltration-high performance liquid chromatography[J]. RSC Advances, 2018, 8: 8944-8949. DOI: 10.1039/C7RA12161J.
[25] CHOI Y, JUNG Y, KIM S N. Identification of eupatilin from Artemisia argyi as a selective PPARɑ agonist using affinity selection ultrafiltration LC-MS[J]. Molecules, 2015, 20(8): 13753-13763. DOI: 10.3390/molecules200813753.
[26] YANG X X, XU F, WANG D, et al. Development of a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method for screening mitochondria-targeted bioactive constituents from complex matrixes: Herbal medicines as a case study[J]. J Chromatogr A, 2015, 1413: 33-46. DOI: 10.1016/j.chroma.2015.08.014.
[27] LIANG L, LI F J, LIU X, et al. Identification of mitochondrial ligands with hepatoprotective activity from Notopterygii Rhizoma et Radix using affinity ultrafiltration/liquid chromatography/mass spectrometry[J]. Biomed Res Int, 2019, 2019: 5729263. DOI: 10.1155/2019/5729263.
[28] CHEN X, XIA Y, LU Y, et al. Screening of permeable compounds in Flos Lonicerae Japonicae with liposome using ultrafiltration and HPLC[J]. J Pharm Biomed Anal, 2011, 54(2): 406-410. DOI: 10.1016/j.jpba.2010.08.028.
[29] 马蕾,王兆伏,陈丽娜,等.红车轴草总异黄酮成分DNA结合剂的超滤质谱筛选[J].高等学校化学学报, 2013, 34(2): 331-335.DOI:10.7503/cjcu20120467.
[30] MULABAGAL V, CALDERON A I. Development of binding assays to screen ligands for Plasmodium falciparum thioredoxin and glutathione reductases by ultrafiltration and liquid chromatography/mass spectrometry[J]. J Chromatogr B, 2010, 878: 987-993. DOI: 10.1016/j.jchromb.2010.02.030.
[31] 唐英,刘春明,李森林,等.黄连中α-葡萄糖苷酶抑制剂的筛选分离及质谱分析[J].天然产物研究与开发, 2016, 28: 1078-1083.DOI:10.16333/j.1001-6880.2016.7.016.
[32] 陈海君,秦惠玉,龙飞,等.超滤亲和结合液相色谱-质谱联用和分子对接技术筛选毛菊苣种子中高亲和性α-葡萄糖苷酶抑制剂[J].分析化学, 2017, 45: 889-897.DOI:10.11895/j.issn.0253-3820.170050.
[33] LI S, LI S, HUANG Y, et al. Ionic-liquid-based ultrasound-assisted extraction of isoflavones from Belamcanda chinensis and subsequent screening and isolation of potential alpha-glucosidase inhibitors by ultrafiltration and semipreparative high-performance liquid chromatography[J]. J Sep Sci, 2017, 40: 2565-2574. DOI: 10.1002/jssc.201700258.
[34] CHEN G, GUO M. Rapid screening for alpha-glucosidase inhibitors from Gymnema sylvestre by affinity ultrafiltration-HPLC-MS[J]. Front Pharmacol, 2017, 8: 228. DOI: 10.3389/fphar.2017.00228.
[35] YANG X, CHEN L, LIU C, et al. Rapid screening, separation, and detection of α-glucosidase inhibitors from Hedyotis diffusa by ultrafiltration-liquid chromatography tandem mass spectrometry-high-speed countercurrent chromatography[J]. Med Chem Res, 2017, 26: 3315-3322. DOI: 10.1007/s00044-017-2024-5.
[36] CHEN H, OUYANG K, JIANG Y, et al. Constituent analysis of the ethanol extracts of Chimonanthus nitens Oliv. leaves and their inhibitory effect on alpha-glucosidase activity[J]. Int. J Biol Macromol, 2017, 98: 829-836. DOI: 10.1016/j.ijbiomac.2017.02.044.
[37] TANG Y, LI S, LI S, et al. Screening and isolating potential α-glucosidase inhibitors from Rhizoma Coptidis by ultrafiltration LC-PDA-ESI/MS combined with high-speed countercurrent chromatography and reverse-phase medium-pressure liquid chromatography[J]. Med Chem Res, 2017, 26: 3384-3394. DOI:10.1007/s00044-017-2031-6.
[38] ZHANG H, ZHANG X, JIANG H, et al. Screening and identification of alpha-glucosidase inhibitors from Shenqi Jiangtang Granule by ultrafiltration liquid chromatography and mass spectrometry[J]. J Sep Sci, 2018, 41(3): 797-805. DOI: 10.1002/jssc.201700835.
[39] NING Z W, ZHAI L X, HUANG T, et al. Identification of alpha-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking[J]. Food Funct, 2019, 10(4): 1893-1902. DOI: 10.1039/c8fo01845f.
[40] ZHANG L, XU L, YE Y, et al. Phytochemical profiles and screening of α-glucosidase inhibitors of four Acer species leaves with ultra-filtration combined with UPLC-QTOF-MS/MS[J]. Ind Crop Prod, 2019, 129: 156-168. DOI:10.1016/j.indcrop.2018.11.051.
[41] XIE L, FU Q, SHI S, et al. Rapid and comprehensive profiling of alpha-glucosidase inhibitors in Buddleja Flos by ultrafiltration HPLC-QTOF-MS/MS with diagnostic ions filtering strategy[J]. Food Chem, 2021, 344: 128651. DOI: 10.1016/j.foodchem.2020.128651.
[42] CAI Y, WU L, LIN X, et al. Phenolic profiles and screening of potential α-glucosidase inhibitors from Polygonum aviculare L. leaves using ultra-filtration combined with HPLC-ESI-qTOF-MS/MS and molecular docking analysis[J]. Ind Crop Prod, 2020, 154: 112673. DOI:10.1016/j.indcrop.2020.112673.
[43] CHEN Y, QI L, ZHONG F, et al. Integrated metabolomics and ligand fishing approaches to screen the hypoglycemic ingredients from four Coptis medicines[J]. J Pharm Biomed Anal, 2021, 192: 113655. DOI: 10.1016/j.jpba.2020.113655.
[44] XIE X, CHEN C, FU X. Screening α-glucosidase inhibitors from four edible brown seaweed extracts by ultra-filtration and molecular docking[J]. LWT, 2021, 138: 110654. DOI: 10.1016/j.lwt.2020.110654.
[45] LIU M, LI X, LIU Q, et al. Comprehensive profiling of α-glucosidase inhibitors from the leaves of Rubus suavissimus using an off-line hyphenation of HSCCC, ultrafiltration HPLC-UV-MS and prep-HPLC[J]. J Food Compos Anal, 2020, 85: 103336. DOI:10.1016/j.jfca.2019.103336.
[46] ZHANG H J, HU Y J, XU P, et al. Screening of potential xanthine oxidase inhibitors in Gnaphalium hypoleucum DC. by immobilized metal affinity chromatography and ultrafiltration-ultra performance liquid chromatography-mass spectrometry[J]. Molecules, 2016, 21(9): 1242. DOI: 10.3390/molecules21091242.
[47] LIU L, XIAO A, MA L, et al. Analysis of xanthine oxidase inhibitors from Puerariae flos using centrifugal ultrafiltration coupled with HPLC-MS[J]. J Brazil Chem Soc, 2016, 28: 360-366. DOI: 10.5935/0103-5053.20160185.
[48] WANG J, SHI D, ZHENG M, et al. Screening, separation, and evaluation of xanthine oxidase inhibitors from Paeonia lactiflora using chromatography combined with a multi-mode microplate reader[J]. J Sep Sci, 2017, 40: 4160-4167. DOI: 10.1002/jssc.201700690.
[49] 谢晶,张晨辉,曾金祥,等.基于液质联用及分子对接技术的短管兔耳草中XOD捕集成分研究[J]. 中国中药杂志, 2018, 43(17): 3595-3603.DOI:10.19540/j.cnki.cjcmm.20180702.005.
[50] LIN L, LIU X, ZHAO M. Screening of xanthine oxidase inhibitor from selected edible plants and hypouricemic effect of rhizoma alpiniae officinarum extract on hyperuricemic rats[J]. J Funct Foods, 2018, 50: 26-36. DOI: 10.1016/j.jff.2018.09.024.
[51] DONG X, WANG B, CAO J, et al. Ligand fishing based on bioaffinity ultrafiltration for screening xanthine oxidase inhibitors from citrus plants[J]. J Sep Sci, 2021, 44(7): 1353-1360. DOI: 10.1002/jssc.202000708.
[52] ZHAO H, ZHOU S, ZHANG M, et al. An in vitro AChE inhibition assay combined with UF-HPLC-ESI-Q-TOF/MS approach for screening and characterizing of AChE inhibitors from roots of Coptis chinensis Franch[J]. J Pharm Biomed Anal, 2016, 120: 235-240. DOI: 10.1016/j.jpba.2015.12.025.
[53] YANG Y, LIANG X, JIN P, et al. Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem-leaf saponins using ultrafiltration(UF)-LC-ESI-MS2[J]. Phytochem Anal, 2019, 30(1): 26-33. DOI: 10.1002/pca.2787.
[54] LIU M, LIU Q, CHEN M, et al. Large-scale separation of acetylcholinesterase inhibitors from Zanthoxylum nitidum by pH-zone-refining counter-current chromatography target-guided by ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry screening[J]. J Sep Sci, 2019, 42(6): 1194-1201. DOI: 10.1002/jssc.201801238.
[55] LI S, LIU C, ZHANG Y, et al. On-line coupling pressurised liquid extraction with two-dimensional counter current chromatography for isolation of natural acetylcholinesterase inhibitors from Astragalus membranaceus[J]. Phytochem Anal, 2021, 32(4): 640-653. DOI: 10.1002/pca.3012.
[56] LIU C, HOU W, LI S, et al. Extraction and isolation of acetylcholinesterase inhibitors from Citrus limon peel using an in vitro method[J]. J Sep Sci, 2020, 43(8): 1531-1543. DOI: 10.1002/jssc.201901252.
[57] ZHANG H, GUO Y, MENG L, et al. Rapid screening and characterization of acetylcholinesterase inhibitors from Yinhuang oral liquid using ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Pharmacogn Mag, 2018, 14(54): 248-252. DOI: 10.4103/pm.pm_166_17.
[58] ZHANG M, ZHAO H, ZHAO Z, et al. Rapid screening, identification, and purification of neuraminidase inhibitors from Lithospermum erythrorhizon Sieb.et Zucc. by ultrafiltration with HPLC-ESI-TOF-MS combined with semipreparative HPLC[J]. J Sep Sci, 2016, 39: 2097-2104. DOI: 10.1002/jssc.201600087.
[59] ZHANG Y, HE Y, LIU C, et al. Screening and isolation of potential neuraminidase inhibitors from leaves of Ligustrum lucidum Ait. based on ultrafiltration, LC/MS, and online extraction-separation methods[J]. J Chromatogr B, 2018, 1083: 102-109. DOI: 10.1016/j.jchromb.2018.03.006.
[60] CAO C X, DU P X, ZHU X M, et al. Rapid screening and purification of potential alkaloid neuraminidase inhibitors from Toddalia asiatica(Linn.)Lam. roots via ultrafiltration liquid chromatography combined with stepwise flow rate counter-current chromatography[J]. J Sep Sci, 2019, 42(16): 2621-2627. DOI: 10.1002/jssc.201900379.
[61] PARK M H, JUNG S, YUK H J, et al. Rapid identification of isoprenylated flavonoids constituents with inhibitory activity on bacterial neuraminidase from root barks of paper mulberry(Broussonetia papyrifera)[J]. Int J Biol Macromol, 2021, 174: 61-68. DOI: 10.1016/j.ijbiomac.2021.01.140.
[62] YIN X S, ZHANG X Q, YIN J T, et al. Screening and identification of potential tyrosinase inhibitors from Semen Oroxyli extract by ultrafiltration LC-MS and in silico molecular docking[J]. J Chromatogr Sci, 2019, 57(9): 838-846. DOI: 10.1093/chromsci/bmz054.
[63] ZHANG H, XU C, TIAN Q H, et al. Screening and characterization of aldose reductase inhibitors from Traditional Chinese medicine based on ultrafiltration-liquid chromatography mass spectrometry and in silico molecular docking[J]. J Ethnopharmacol, 2021, 264: 113282. DOI: 10.1016/j.jep.2020.113282.
[64] WANG Z Q, HWANG S H, GUILLEN QUISPE Y N, et al. Investigation of the antioxidant and aldose reductase inhibitory activities of extracts from Peruvian tea plant infusions[J]. Food Chem, 2017, 231: 222-230. DOI: 10.1016/j.foodchem.2017.03.107.
[65] WANG Z Q, HWANG S H, LIM S S. Characterization of DHDP, a novel aldose reductase inhibitor isolated from Lysimachia christinae[J]. J Funct Foods, 2017, 37: 241-248. DOI:10.1016/j.jff.2017.07.057.
[66] WANG Z Q, GUILLEN QUISPE Y N, HWANG S H, et al. Pistafolin B is the major aldose reductase inhibitor of the pods of tara[Caesalpinia spinose(Molina)Kuntze] [J]. Ind Crop Prod, 2018, 122: 709-715. DOI:10.1016/j.indcrop.2018.06.023.
[67] WANG Z Q, SHEN S G, CUI Z, et al. Screening and isolating major aldose reductase inhibitors from the seeds of evening primrose(Oenothera biennis)[J]. Molecules, 2019, 24(15): 2709. DOI: 10.3390/molecules24152709.
[68] TANG Y, LI S L, LI S N, et al. Screening and isolation of potential lactate dehydrogenase inhibitors from five Chinese medicinal herbs: Soybean, Radix pueraria, Flos pueraria, Rhizoma belamcandae, and Radix astragali[J]. J Sep Sci, 2016, 39(11): 2043-2049. DOI: 10.1002/jssc.201600050.
[69] LI S L, LI S N, TANG Y, et al. Ultrafiltration-LC-MS combined with semi-preparative HPLC for the simultaneous screening and isolation of lactate dehydrogenase inhibitors from Belamcanda chinensis[J]. J Sep Sci, 2016, 39(23): 4533-4543. DOI: 10.1002/jssc.201600703.
[70] LIU C, LI S, TSAO R, et al. Extraction and isolation of potential anti-stroke compounds from black soybean(Glycine max L. Merrill)guided by in vitro PC12 cell model[J]. J Funct Foods, 2017, 31: 295-303. DOI:10.1016/j.jff.2017.02.011.
[71] LI S N, ZHANG J X, LI S L, et al. Extraction and separation of lactate dehydrogenase inhibitors from Poria cocos(Schw.)Wolf based on a hyphenated technique and in vitro methods[J]. J Sep Sci, 2017, 40(8): 1773-1783. DOI: 10.1002/jssc.201700054.
[72] LI S N, LI S L, LIU C Y, et al. Extraction and isolation of potential anti-stroke compounds from flowers of Pueraria lobata guided by in vitro PC12 cell model[J]. J Chromatogr B, 2017, 1048: 111-120. DOI: 10.1016/j.jchromb.2017.02.009.
[73] HUAI J X, ZHAO X N, WANG S Q, et al. Characterization and screening of cyclooxygenase-2 inhibitors from Zi-shen pill by affinity ultrafiltration-ultra performance liquid chromatography mass spectrometry[J]. J Ethnopharmacol, 2019, 241: 111900. DOI: 10.1016/j.jep.2019.111900.
[74] JIAO J J, YANG Y Z, WU Z F, et al. Screening cyclooxygenase-2 inhibitors from Andrographis paniculata to treat inflammation based on bio-affinity ultrafiltration coupled with UPLC-Q-TOF-MS[J]. Fitoterapia, 2019, 137: 104259. DOI: 10.1016/j.fitote.2019.104259.
[75] LI S, ZHANG Y, SHI D, et al. Screening and isolation of cyclooxygenase-2 inhibitors from the stem bark of Phellodendron amurense Ruprecht by ultrafiltration with liquid chromatography and tandem mass spectrometry, and complex chromatography[J]. J Sep Sci, 2019, 42(10): 1905-1914. DOI: 10.1002/jssc.201801262.
[76] ZHANG X Y, WEI Z J, QIAO W L, et al. Discovery of cyclooxygenase-2 inhibitors from Kadsura coccinea by affinity ultrafiltration mass spectrometry and the anti-inflammatory activity[J]. Fitoterapia, 2021, 151: 104872. DOI: 10.1016/j.fitote.2021.104872.
[77] CEN Y, XIAO A, CHEN X, et al. Isolation of alpha-amylase inhibitors from Kadsura longipedunculata using a high-speed counter-current chromatography target guided by centrifugal ultrafiltration with LC-MS[J]. Molecules, 2016, 21(9): 1190. DOI: 10.3390/molecules21091190.
[78] LIAO L P, CHEN J, LIU L L, et al. Screening and binding analysis of flavonoids with alpha-amylase inhibitory activity from Lotus leaf[J]. J Brazil Chem Soc, 2017, 29: 1-7. DOI:10.21577/0103-5053.20170171.
[79] MA C, HU L, KOU X, et al. Rapid screening of potential α-amylase inhibitors from Rhodiola rosea by UPLC-DAD-TOF-MS/MS-based metabolomic method[J]. J Funct Foods, 2017, 36: 144-149. DOI: 10.1016/j.jff.2017.06.060.
[80] CHEN G, TIAN Y, GUO M. Screening for inhibitors of topoisomerase I from Lycoris radiata by combining ultrafiltration with liquid chromatography/mass spectrometry[J]. Rapid Commun Mass Spectrom, 2016, 30(S1): 95-99. DOI:10.1002/rcm.7649.
[81] CHEN G L, TIAN Y Q, WU J L, et al. Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I[J]. Sci Rep, 2016, 6: 38284. DOI: 10.1038/srep38284.
[82] CHEN G, GUO M. Screening for natural inhibitors of topoisomerases I from Rhamnus davurica by affinity ultrafiltration and high-performance liquid chromatography-mass spectrometry[J]. Front Plant Sci, 2017, 8: 1521. DOI: 10.3389/fpls.2017.01521.
[83] FANG Y X, SONG H P, LIANG J X, et al. Rapid screening of pancreatic lipase inhibitors from Monascus-fermented rice by ultrafiltration liquid chromatography-mass spectrometry[J]. Anal Methods, 2017, 9(23): 3422-3429. DOI: 10.1039/C7AY00777A.
[84] YANG J, QI Y, LI H, et al. Determination of quinic acids in Helichrysum arenarium(L.)Moench by ultrafiltration affinity and ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UF-UPLC-Q-TOF-MS)[J]. Anal Lett, 2020, 54: 772-789. DOI: 10.1080/00032719.2020.1781876.
[85] ZHAO A Q, LI L, LI B, et al. Ultrafiltration LC-ESI-MSn screening of 5-lipoxygenase inhibitors from selected Chinese medicinal herbs Saposhnikovia divaricata, Smilax glabra, Pueraria lobata and Carthamus tinctorius[J]. J Funct Foods, 2016, 24: 244-253. DOI:10.1016/j.jff.2016.04.011.
[86] WANG S Q, HUAI J X, SHANG Y, et al. Screening for natural inhibitors of 5-lipoxygenase from Zi-shen pill extract by affinity ultrafiltration coupled with ultra performance liquid chromatography-mass spectrometry[J]. J Ethnopharmacol, 2020, 254: 112733. DOI: 10.1016/j.jep.2020.112733.
[87] ZHANG Q, YANG Y X, LI S Y, et al. An ultrafiltration and high performance liquid chromatography coupled with diode array detector and mass spectrometry approach for screening and characterizing thrombin inhibitors from Rhizoma Chuanxiong[J]. J Chromatogr B, 2017, 1061/1062: 421-429. DOI: 10.1016/j.jchromb.2017.07.050.
[88] JIN Y, CHENG X H, JIANG F Q, et al. Application of the ultrafiltration-based LC-MS approach for screening PTP1B inhibitors from Chinese red yeast rice[J]. Anal Methods, 2016,8(2): 353-361. DOI: 10.1039/C5AY01767J.
[89] ZHANG Y C, HE Y, LIU C Y, et al. In vitro screening and isolation of human aromatase inhibitors from Cicer arietinum by a novel continuous online method combining chromatographic techniques[J]. J Sep Sci, 2018, 41(2): 483-492. DOI: 10.1002/jssc.201700990.
[90] LIU Z C, LIN Z T, CHEN S Z, et al. Rapid screening of potential phosphodiesterase inhibitors from the roots of Ilex pubescens Hook. et arn. using a combination of ultrafiltration and LC-MS[J]. Evid Based Complement Alternat Med, 2017, 2017: 2749643. DOI: 10.1155/2017/2749643.
[91] WU S Q, SONG H P, LI B, et al. A fast and accurate method for the identification of peroxidase inhibitors from Radix Salvia Miltiorrhizae by on-flow biochemical assay coupled with LC/Q-TOF-MS: comparison with ultrafiltration-based affinity selection[J]. Anal Bioanal Chem, 2018, 410(18): 4311-4322. DOI: 10.1007/s00216-018-1081-z.
[92] WANG Y, HONG F, LI D, et al. A novel strategy for evaluation of natural products acting on the myeloperoxidase/hypochlorous acid system by combining high-performance liquid chromatography-photodiode array detection-chemiluminescence and ultrafiltration-mass spectrometry techniques[J]. J Sep Sci, 2018, 41(22): 4222-4232. DOI: 10.1002/jssc.201800658.
[93] LI L, KONG J, YAO C H, et al. Rapid identification of urokinase plasminogen activator inhibitors from Traditional Chinese Medicines based on ultrafiltration, LC-MS and in silico docking[J]. J Pharm Biomed Anal, 2019, 164: 241-248. DOI: 10.1016/j.jpba.2018.10.036.
[94] GUO Y, FU R, QIAN Y, et al. Comprehensive screening and identification of natural inducible nitric oxide synthase inhibitors from Radix Ophiopogonis by off-line multi-hyphenated analyses[J]. J Chromatogr A, 2019, 1592: 55-63. DOI: 10.1016/j.chroma.2019.01.029.
[95] HUANG Y, YU M, WU T, et al. Development of a method to screen and isolate lipoxidase inhibitors from Radix Saposhnikoviae via ultrafiltration liquid chromatography combined with metablism in vitro[J]. Phytochem Anal, 2020, 31(6): 937-947. DOI: 10.1002/pca.2966.
[96] HE Y, WANG Y, ZHANG X, et al. Chemical characterization of small-molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry[J]. Rapid Commun Mass Spectrom, 2020, 34(8): e8694. DOI: 10.1002/rcm.8694.
[97] ZHAO D F, FAN Y F, WANG F Y, et al. Discovery and characterization of naturally occurring potent inhibitors of catechol-O-methyltransferase from herbal medicines[J]. RSC Advances, 2021,11(17):10385-10392. DOI: 10.1039/DORA10425F.
[98] 付旭,李利新,汪志华,等.利用亲和质谱技术从中药材提取物中筛选马尔堡病毒核蛋白的小分子配体[J].南开大学学报自然科学版, 2016, 49(5): 1-7.
[99] 高岩,秦卫卫,葛跃伟,等.对照亲和超滤液质联用和分子对接技术筛选博落回种子中的G-四链体配体[J].中国中药杂志, 2020, 45(16): 3908-3914.
[100] WANG Y Q, TANG Y, LIU C M, et al. Determination and isolation of potential α-glucosidase and xanthine oxidase inhibitors from Trifolium pratense L. by ultrafiltration liquid chromatography and high-speed countercurrent chromatography[J]. Med Chem Res, 2016, 25: 1020-1029. DOI: 10.1007/s00044-016-1548-4.
[101] FU X, WANG Z H, LI L X, 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. DOI: 10.1038/srep29680.
[102] CHEN G L, WU J L, LI N, et al. Screening for anti-proliferative and anti-inflammatory components from Rhamnus davurica Pall. using bio-affinity ultrafiltration with multiple drug targets[J]. Anal Bioanal Chem, 2018, 410: 3587-3595. DOI: 10.1007/s00216-018-0953-6.
[103] HOU W C, XIA J L, LIU C M, et al. Development of a method to screen and isolate bioactive constituents from Stellera chamaejasme by ultrafiltration and liquid chromatography combined with semi-preparative high-performance liquid chromatography and high-speed counter current chromatography[J]. J Sep Sci, 2019, 42: 3421-3431. DOI: 10.1002/jssc.201900772.
[104] XIE L, LEE D Y, SHANG Y, et al. Characterization of spirostanol glycosides and furostanol glycosides from anemarrhenae rhizoma as dual targeted inhibitors of 5-lipoxygenase and Cyclooxygenase-2 by employing a combination of affinity ultrafiltration and HPLC/MS[J]. Phytomedicine, 2020, 77: 153284. DOI: 10.1016/j.phymed.2020.153284.
[105] CHEN G L, XU Y B, WU J L, et al. Hypoglycemic and hypolipidemic effects of Moringa oleifera leaves and their functional chemical constituents[J]. Food Chem, 2020, 333: 127478. DOI: 10.1016/j.foodchem.2020.127478.
[106] ZHUANG X C, CHEN G L, LIU Y, et al. New lignanamides with antioxidant and anti-inflammatory activities screened out and identified from Warburgia ugandensis combining affinity ultrafiltration LC-MS with SOD and XOD enzymes[J]. Antioxidants(Basel), 2021, 10: 370. DOI: 10.3390/antiox10030370.
[107] CHEN G L, GUO M Q. Rapid re-evaluation of bioactive saponins from Paris polyphylla using affinity ultrafiltration-LC/MS with multiple drug targets[J]. Int J Mass Spectrom, 2018, 434: 87-92. DOI:10.1016/j.ijms.2018.09.016.
[108] WU T, LIU C M, HUANG Y, et al. Simultaneous screening and isolation of activated constituents from Puerariae Flos by ultrafiltration with liquid chromatography and mass spectrometry combined with high-speed counter-current chromatography[J]. J Sep Sci, 2018, 41(24): 4458-4468. DOI: 10.1002/jssc.201800691.
[109] ZHUANG X C, ZHANG Y L, CHEN G L, et al. Identification of anti-inflammatory and anti-proliferative neolignanamides from Warburgia ugandensis employing multi-target affinity ultrafiltration and LC-MS[J]. Pharmaceuticals(Basel), 2021, 14: 313. DOI: 10.3390/ph14040313. (