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.

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.

• Authors: Laiyou Wang, Weiye Tao, Duosheng Luo, Yinming Hu, Weijian Bei, Jiao Guo
• Journal: Complementary therapies in medicine (Complement Ther Med) Vol. 22 Issue 5 Pg. 887-93 (Oct 2014) ISSN: 1873-6963 [Electronic] Scotland
• PMID: 25440380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• FTZ formula
• Lipid Regulating Agents
• Lipids

Topics

• Animals
• Drug Synergism
• Drugs, Chinese Herbal (pharmacokinetics, pharmacology)
• Lipid Metabolism (drug effects)
• Lipid Regulating Agents (blood, pharmacokinetics, pharmacology)
• Lipids (blood)
• Liver (drug effects, metabolism)
• Metabolic Networks and Pathways
• Molecular Docking Simulation
• Rats