title: In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury.
abstract: This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.
authors.affiliation: Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130012, China. gyl197908@163.com.
authors.forename: Guo-Yu
authors.initials: GY
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. zhengyaxinxyz@163.com.
authors.forename: Ya-Xin
authors.initials: YX
authors.lastname: Zheng
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. sunfuzhou1989@126.com.
authors.forename: Fu-Zhou
authors.initials: FZ
authors.lastname: Sun
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. profhj@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Shihezi University, Shihezi 832002, China. lmm198508@163.com.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Lou
authors.affiliation: Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130012, China. gujk@mail.jlu.edu.cn.
authors.forename: Jing-Kai
authors.initials: JK
authors.lastname: Gu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. profwjh@126.com.|School of Pharmacy, Shihezi University, Shihezi 832002, China. profwjh@126.com.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001665:Binding Sites; D020170:Caspase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D018651:Cichorium intybus / Q000737:chemistry*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D010936:Plant Extracts; D054852:Small Molecule Libraries; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020170:Caspase 1
keywords: Akt-1; Cichorium intybus L.; acute liver injury; caspase-1; in silico analysis