title: Identification of bio-active metabolites of gentiopicroside by UPLC/Q-TOF MS and NMR.
abstract: Gentiopicroside (GPS), the main bioactive component in Gentiana scabra Bge., has attracted our attention owing to its high bioactivity, especially the treatment of hepatobiliary disorders. The aglycone form of GPS, a typical secoiridoid glycoside, is considered to be more readily absorbed than its parent drug. This study aimed to identify and characterize the metabolites after GPS incubated with β-glucosidase in buffer solution at 37°C. Samples of biotransformed solution were collected and analyzed by ultraperformance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (Q-TOF MS). A total of four metabolites were detected: two were isolated and elucidated by preparative-HPLC and NMR techniques, and one of those four is reported for the first time. The mass spectral fragmentation pattern and accurate masses of metabolites were established on the basis of UPLC/Q-TOF MS analysis. Structure elucidation of metabolites was achieved by comparing their fragmentation pattern with that of the parent drug. A fairly possible metabolic pathway of GPS by β-glucosidase was proposed. The hepatoprotective activities of metabolites M1 and M2 were investigated and the results showed that their hepatoprotective activities were higher than that of parent drug. Our results provided a meaningful basis for discovering lead compounds from biotransformation related to G. scabra Bge. in traditional Chinese medicine.
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine, Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zeng
authors.forename: Han
authors.initials: H
authors.lastname: Han
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Tao
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
mesh_terms: D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D057888:Iridoid Glucosides / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D053858:Metabolic Networks and Pathways; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D020011:Protective Agents / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D004365:Drugs, Chinese Herbal; D057888:Iridoid Glucosides; D020011:Protective Agents; C012997:gentiopicroside
keywords: UPLC/Q-TOF MS; gentiopicroside; hepatoprotective activity; metabolites; β-glucosidase