文献类型：期刊文献

英文题名：Isolation and bioactive evaluation of flavonoid glycosides from Lobelia chinensis Lour using two-dimensional liquid chromatography combined with label-free cell phenotypic assays

作者：Wang, Jixia[1,5];Chen, Linlin[2];Qu, Lala[1,3];Li, Kuiyong[4];Zhao, Yaopeng[1,5];Wang, Zhiwei[5];Li, Yuan[2];Zhang, Xiuli[1,6];Jin, Yu[4];Liang, Xinmiao[1,5,6]

机构：[1]Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China;[2]Fudan Univ, Shanghai Canc Ctr, Pathol, Shanghai 200237, Peoples R China;[3]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[4]East China Univ Sci & Technol, Minist Educ, Sch Pharm, Engn Res Ctr Pharmaceut Proc Chem, Shanghai 200237, Peoples R China;[5]DICP CMC Innovat Inst Med, Taizhou 225300, Peoples R China;[6]Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226019, Peoples R China

年份：2019

卷号：1601

起止页码：224

外文期刊名：JOURNAL OF CHROMATOGRAPHY A

收录：;EI(收录号：20192006924164);WOS:【SCI-EXPANDED(收录号:WOS:000477685700025)】；

基金：This work was supported by the State Key Program of National Natural Science of China (Grant No. U1508221), Project of National Science Foundation of China (81803706) and the funding for the construction of DICP-CMC Innovation Institute of Medicine.

语种：英文

外文关键词：Flavonoid glycosides; Separation and purification; G protein-coupled receptor 35; Two-dimensional liquid chromatography; Label-free cell phenotypic assays

摘要：Flavonoid glycosides are widespread in herbs and often used as medicines and nutraceuticals because of good bioactivities and low toxicities. However, due to their structural complexity and diversity, isolation of flavonoid glycosides and evaluation of their bioactivities are still highly challenging. To solve this problem, a new method for separation and preparation of novel flavonoid glycosides from Lobelia chinensis Lour (L. chinensis) was developed. To avoid the interference of non-flavonoids, a solid phase extraction method was used to selectively enrich the flavonoids from the total extract. Based on hydrophilic and hydrophobic properties of the flavonoid chemical structure consisting of sugar residue and diphenylpropane (C6C3C6) skeleton, a structure-guided method development strategy was employed to design a 2D-HILIC x RPLC system in the first time. After optimization of chromatographic conditions, high selectivity and symmetric peaks of flavonoids were obtained on a zwitterionic Click XIon column and a polar-modified Atlantis T3 column. Based on these two columns, a 2 D-HILIC x RPLC system was constructed and successfully enlarged from the analytical level to the preparative level. In the first dimension, 20 fractions were obtained with good peak shapes at high sample loading. In the second-dimensional preparation, nine compounds were isolated and identified. Seven of them were novel flavonoid glycosides, lobelitin A-G, and two other known compounds were linatin and diosmin, respectively. Their target activities were evaluated via label-free cell phenotypic assays. Four novel flavonoid glycosides lobelitin A-D were found to have agonistic activities at G protein-coupled receptor 35 (GPR35). These results demonstrated that this method was effective to orthogonally separate flavonoids at the preparative level, especially for novel active flavonoid glycosides. The discovery of flavonoid glycosides with novel agonistic activity on GPR35 also sheds light on the mechanisms of action of L. chinensis relevant to its clinical application. (C) 2019 Elsevier B.V. All rights reserved.