Discovery of beta(2)-adrenoceptor agonists in Curcuma zedoaria Rosc using label-free cell phenotypic assay combined with two-dimensional liquid chromatography

doi:10.1016/j.chroma.2018.09.053

	Discovery of beta(2)-adrenoceptor agonists in Curcuma zedoaria Rosc using label-free cell phenotypic assay combined with two-dimensional liquid chromatography
	Liu, Yanfang 1; Liang, Xinmiao 1,4; Zhou, Weijia 1,2; Wang, Jixia 1; Zhao, Yaopeng 1; Yu, Long 1; Fang, Ye 3; Jin, Hongli 1; Zhou, Han 1; Zhang, Pengyu 1
刊名	JOURNAL OF CHROMATOGRAPHY A
	2018-11-23
卷号	1577 页码:59-65
关键词	Curcuma zedoaria Rosc beta(2)-adrenoceptor agonists Diarylheptanoids Label-free cell phenotypic assay Two-dimensional liquid chromatography
ISSN号	0021-9673
DOI	10.1016/j.chroma.2018.09.053
通讯作者	Liu, Yanfang(liuyanfang@dicp.ac.cn) ; Zhang, Xiuli(zhangxiuli@dicp.ac.cn) ; Liang, Xinmiao(liangxm@dicp.ac.cn)
英文摘要	Traditional Chinese Medicines (TCMs) have been widely used in clinical practice, and provided a rich source for discovering new drug leads. However, efficient identification of active molecules responsible for the therapeutic effects of complex TCMs is still highly challenging. Here, we combined label-free cell phenotypic assay with two dimensional liquid chromatography (2DLC) to identify potential beta(2)-adrenoceptor (beta(2)-AR) agonists related to anti-asthmatic effect of Curcuma zedoaria Rosc (C.zedoaria), a commonly used TCM. The ethyl acetate extract of C.zedoaria was first fractionated into 26 fractions. Label free cell phenotypic profiling was then used to locate the active sites. Orthogonal second-dimensional (D2) separation was performed on two fractions displaying agonistic effect at the beta(2)-AR, combined with screening of the D2 fractions to track the activity. Finally, this approach led to the isolation of three known diarylheptanoids, among which diarylheptanoid b exhibited the most potent agonistic activity with an EC50 value of 5.93 mu M. This result was further demonstrated through the chemical synthesis of diarylheptanoid b. It is the first time to discover that diarylheptanoids could activate the beta(2)-AR, which may be responsible for the anti -asthmatic effect of C.zedoaria observed traditionally and in clinical application. This study also demonstrates the potential of this integrated strategy for identifying active ingredients and determining the basis of therapeutic materials in complex TCMs. (C) 2018 Elsevier B.V. All rights reserved.
资助项目	State Key Program of National Natural Science of China[U1508221] ; Project of National Science Foundation of China[81473436] ; Project of National Science Foundation of China[31670374] ; Project of National Science Foundation of China[81803706] ; DICP, CAS[DICP TMSR201601]
WOS关键词	FLIGHT MASS-SPECTROMETRY ; IDENTIFICATION ; EXTRACT ; CONSTITUENTS ; COMPONENTS ; INHIBITORS ; MEDICINE ; EFFICACY ; DRUGS
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000452343500008
资助机构	State Key Program of National Natural Science of China ; State Key Program of National Natural Science of China ; Project of National Science Foundation of China ; Project of National Science Foundation of China ; DICP, CAS ; DICP, CAS ; State Key Program of National Natural Science of China ; State Key Program of National Natural Science of China ; Project of National Science Foundation of China ; Project of National Science Foundation of China ; DICP, CAS ; DICP, CAS ; State Key Program of National Natural Science of China ; State Key Program of National Natural Science of China ; Project of National Science Foundation of China ; Project of National Science Foundation of China ; DICP, CAS ; DICP, CAS ; State Key Program of National Natural Science of China ; State Key Program of National Natural Science of China ; Project of National Science Foundation of China ; Project of National Science Foundation of China ; DICP, CAS ; DICP, CAS
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166416]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Liu, Yanfang; Liang, Xinmiao; Zhang, Xiuli
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100000, Peoples R China 3.Corning Inc, Biochem Technol Sci & Technol Div, Corning, NY 14831 USA 4.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226019, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yanfang,Liang, Xinmiao,Zhou, Weijia,et al. Discovery of beta(2)-adrenoceptor agonists in Curcuma zedoaria Rosc using label-free cell phenotypic assay combined with two-dimensional liquid chromatography[J]. JOURNAL OF CHROMATOGRAPHY A,2018,1577:59-65.
APA	Liu, Yanfang.,Liang, Xinmiao.,Zhou, Weijia.,Wang, Jixia.,Zhao, Yaopeng.,...&Zhang, Xiuli.(2018).Discovery of beta(2)-adrenoceptor agonists in Curcuma zedoaria Rosc using label-free cell phenotypic assay combined with two-dimensional liquid chromatography.JOURNAL OF CHROMATOGRAPHY A,1577,59-65.
MLA	Liu, Yanfang,et al."Discovery of beta(2)-adrenoceptor agonists in Curcuma zedoaria Rosc using label-free cell phenotypic assay combined with two-dimensional liquid chromatography".JOURNAL OF CHROMATOGRAPHY A 1577(2018):59-65.