title: Potential synergistic effects of Chinese herbal prescription FTZ components detected in blood towards hepatic lipid-modulating targets.
abstract: OBJECTIVE
  Our goal in this study aims to explain the polypharmacological mechanism at the molecular level responsible for the effectiveness of a traditional Chinese medicine (TCM) prescription FTZ to treat hyperlipidemia and related disease.
  
  
  METHODS
  By MDL(®) ISIS_Base 2.5, we constructed a compound database based on the FTZ constituents, which were detected in the rat serum after oral administration of the TCM through ultra-performance liquid chromatography/quadruple-time-of-flight mass-spectrometry (UPLC/Q-TOF-MS/MS) method. After validation of the virtual docking system, we used molecular screening by LigandFit which is a computational method for the shape-directed rapid docking of ligands to target protein active sites, to investigate the interactions between the components in database and lipid-modulating targets in the liver.
  
  
  RESULTS
  In the prescription FTZ ingredients, there were sixteen constituents including jatrorrhizine, etc. showed potential effects towards the hyperlipidemia-related targets: HMG-CoA reductase (HMGR), squalene synthase (SQS), oxidosqualene cyclase (OSC), cholesteryl ester transfer protein (CETP), liver X receptor (LXR), farnesoid X receptor (FXR) and peroxisome proliferator-activated receptors (PPARα and PPARγ). Among the eight herbs in prescription FTZ, Rhizoma Coptidis (RC) plays the most important role in whole effect from FTZ on hyperlipidemia related disease.
  
  
  CONCLUSIONS
  Our research demonstrated that Chinese medicine formula FTZ has multi-target synergistic effect on hyperlipidemia and suggests the pharmacodynamic material basis could be jatrorrhizine, berberrubine, berberine and salidroside.
authors.affiliation: Key Unit of Modulating Liver to Treat Hyperlipidemia SATCM, Level 3 Lab of Lipid Metabolism SATCM, Guangdong TCM Key Laboratory against Metabolic Diseases, Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Laiyou
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Weiye
authors.initials: W
authors.lastname: Tao
authors.affiliation: Key Unit of Modulating Liver to Treat Hyperlipidemia SATCM, Level 3 Lab of Lipid Metabolism SATCM, Guangdong TCM Key Laboratory against Metabolic Diseases, Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Duosheng
authors.initials: D
authors.lastname: Luo
authors.affiliation: Key Unit of Modulating Liver to Treat Hyperlipidemia SATCM, Level 3 Lab of Lipid Metabolism SATCM, Guangdong TCM Key Laboratory against Metabolic Diseases, Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Yinming
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Unit of Modulating Liver to Treat Hyperlipidemia SATCM, Level 3 Lab of Lipid Metabolism SATCM, Guangdong TCM Key Laboratory against Metabolic Diseases, Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Bei
authors.affiliation: Key Unit of Modulating Liver to Treat Hyperlipidemia SATCM, Level 3 Lab of Lipid Metabolism SATCM, Guangdong TCM Key Laboratory against Metabolic Diseases, Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China. Electronic address: jiaoguo_gdpu@hotmail.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
mesh_terms: D000818:Animals; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D057847:Lipid Regulating Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D062105:Molecular Docking Simulation; D051381:Rats
chemical_list: D004365:Drugs, Chinese Herbal; C000591284:FTZ formula; D057847:Lipid Regulating Agents; D008055:Lipids
keywords: Hyperlipidemia; Molecular docking; Multi-target therapeutics; Polypharmacology; Virtual screening