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Isolation and bioactive evaluation of flavonoid glycosides from Lobelia chinensis Lour using two-dimensional liquid chromatography combined with label-free cell phenotypic assays.
J Chromatogr A 2019; 1601:224-231JC

Abstract

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 × 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 × 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.

Authors+Show Affiliations

Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; DICP-CMC Innovation Institute of Medicine, Taizhou 225300, China.Pathology, Fudan University Shanghai Cancer Center, Shanghai 200237, China.Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; DICP-CMC Innovation Institute of Medicine, Taizhou 225300, China.DICP-CMC Innovation Institute of Medicine, Taizhou 225300, China.Pathology, Fudan University Shanghai Cancer Center, Shanghai 200237, China.Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China. Electronic address: zhangxiuli@dicp.ac.cn.Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: jiny@ecust.edu.cn.Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; DICP-CMC Innovation Institute of Medicine, Taizhou 225300, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China. Electronic address: liangxm@dicp.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31101464

Citation

Wang, Jixia, et al. "Isolation and Bioactive Evaluation of Flavonoid Glycosides From Lobelia Chinensis Lour Using Two-dimensional Liquid Chromatography Combined With Label-free Cell Phenotypic Assays." Journal of Chromatography. A, vol. 1601, 2019, pp. 224-231.
Wang J, Chen L, Qu L, et al. Isolation and bioactive evaluation of flavonoid glycosides from Lobelia chinensis Lour using two-dimensional liquid chromatography combined with label-free cell phenotypic assays. J Chromatogr A. 2019;1601:224-231.
Wang, J., Chen, L., Qu, L., Li, K., Zhao, Y., Wang, Z., ... Liang, X. (2019). Isolation and bioactive evaluation of flavonoid glycosides from Lobelia chinensis Lour using two-dimensional liquid chromatography combined with label-free cell phenotypic assays. Journal of Chromatography. A, 1601, pp. 224-231. doi:10.1016/j.chroma.2019.04.073.
Wang J, et al. Isolation and Bioactive Evaluation of Flavonoid Glycosides From Lobelia Chinensis Lour Using Two-dimensional Liquid Chromatography Combined With Label-free Cell Phenotypic Assays. J Chromatogr A. 2019 Sep 13;1601:224-231. PubMed PMID: 31101464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isolation and bioactive evaluation of flavonoid glycosides from Lobelia chinensis Lour using two-dimensional liquid chromatography combined with label-free cell phenotypic assays. AU - Wang,Jixia, AU - Chen,Linlin, AU - Qu,Lala, AU - Li,Kuiyong, AU - Zhao,Yaopeng, AU - Wang,Zhiwei, AU - Li,Yuan, AU - Zhang,Xiuli, AU - Jin,Yu, AU - Liang,Xinmiao, Y1 - 2019/05/01/ PY - 2019/03/01/received PY - 2019/04/29/revised PY - 2019/04/30/accepted PY - 2019/5/19/pubmed PY - 2019/7/25/medline PY - 2019/5/19/entrez KW - Flavonoid glycosides KW - G protein-coupled receptor 35 KW - Label-free cell phenotypic assays KW - Separation and purification KW - Two-dimensional liquid chromatography SP - 224 EP - 231 JF - Journal of chromatography. A JO - J Chromatogr A VL - 1601 N2 - 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 × 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 × 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. SN - 1873-3778 UR - https://www.unboundmedicine.com/medline/citation/31101464/Isolation_and_bioactive_evaluation_of_flavonoid_glycosides_from_Lobelia_chinensis_Lour_using_two-dimensional_liquid_chromatography_combined_with_label-free_cell_phenotypic_assays L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9673(19)30476-5 DB - PRIME DP - Unbound Medicine ER -