Laiyou Wang1, Weiye Tao2, Duosheng Luo1, Yinming Hu1, Weijian Bei1, Jiao Guo3. 1. 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. 2. College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China. 3. 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.
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. DESIGN: 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.
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. DESIGN: 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.