title: Nontargeted metabolomic analysis and "commercial-homophyletic" comparison-induced biomarkers verification for the systematic chemical differentiation of five different parts of Panax ginseng.
abstract: A key segment in authentication of herbal medicines is the establishment of robust biomarkers that embody the intrinsic metabolites difference independent of the growing environment or processing technics. We present a strategy by nontargeted metabolomics and "Commercial-homophyletic" comparison-induced biomarkers verification with new bioinformatic vehicles, to improve the efficiency and reliability in authentication of herbal medicines. The chemical differentiation of five different parts (root, leaf, flower bud, berry, and seed) of Panax ginseng was illustrated as a case study. First, an optimized ultra-performance liquid chromatography/quadrupole time-of-flight-MS(E) (UPLC/QTOF-MS(E)) approach was established for global metabolites profiling. Second, UNIFI™ combined with search of an in-house library was employed to automatically characterize the metabolites. Third, pattern recognition multivariate statistical analysis of the MS(E) data of different parts of commercial and homophyletic samples were separately performed to explore potential biomarkers. Fourth, potential biomarkers deduced from commercial and homophyletic root and leaf samples were cross-compared to infer robust biomarkers. Fifth, discriminating models by artificial neutral network (ANN) were established to identify different parts of P. ginseng. Consequently, 164 compounds were characterized, and 11 robust biomarkers enabling the differentiation among root, leaf, flower bud, and berry, were discovered by removing those structurally unstable and possibly processing-related ones. The ANN models using the robust biomarkers managed to exactly discriminate four different parts and root adulterant with leaf as well. Conclusively, biomarkers verification using homophyletic samples conduces to the discovery of robust biomarkers. The integrated strategy facilitates authentication of herbal medicines in a more efficient and more intelligent manner.
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China; School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Boshuo Road 1035, Changchun 130117, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Yang
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Chang-Liang
authors.initials: CL
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Boshuo Road 1035, Changchun 130117, China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Qiu
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Shi
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Jing-Xian
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Hou
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Qiu-Rong
authors.initials: QR
authors.lastname: Wang
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: wanyingwu@simm.ac.cn.
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Wu
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: daguo@simm.ac.cn.
authors.forename: De-An
authors.initials: DA
authors.lastname: Guo
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D005894:Panax / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers
keywords: Artificial neutral network; Panax ginseng; Robust biomarker; UNIFI™; Ultra-performance liquid chromatography/quadrupole time-of-flight-MS(E); “Commercial-homophyletic” comparison