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Pharm Res (2014) 31:17881800 DOI 10.1007/s11095-013-1283-1
RESEARCH PAPER
Bioactive Equivalence of Combinatorial Components Identified in Screening of an Herbal Medicine
Peng Liu & Hua Yang & Fang Long & Hai-Ping Hao & Xiaojun Xu & Ying Liu & Xiao-Wei Shi & Dan-Dan Zhang & Hao-Chuan Zheng &
Qian-Ying Wen & Wen-Wen Li & Hui Ji & Xi-Juan Jiang & Bo-Li Zhang & Lian-Wen Qi & Ping Li
Received: 21 October 2013 /Accepted: 31 December 2013 /Published online: 19 February 2014 # The Author(s) 2014. This article is published with open access at Springerlink.com
ABSTRACTPurpose To identify bioactive equivalent combinatorial components (BECCs) in herbal medicines. The exact composition of effective components in herbal medicines is often elusive due to the lack of adequate screening methodology. Herein, we propose a hypothesis that BECCs accounting for the whole efficacy of original herbal medicines could be discovered from a complex mixture of constituents.
Methods We developed a bioactive equivalence oriented feedback screening method and applied it to discover the BECCs from an herbal preparation Cardiotonic Pill (CP). The operations include chemical profiling of CP, followed by an iterative loop of determining, collecting and evaluating candidate BECCs. Results A combination of 18 compounds was identified as BECCs from CP, which accounts for 15.0% (w/w) of original CP. We have demonstrated that the BECCs were as effective as CP in cell models and in a rat model of myocardial infarction. Conclusions This work answers the key question of which are real bioactive components for CP that have been used in clinic for many years, and provides a promising approach for discovering BECCs from herbal medicines. More importantly, the BECCs could be extended to improve quality control of herbal products and inspire an herbal medicines based discovery of combinatorial therapeutics.
KEY WORDS bioactive equivalence . Cardiotonic Pill . combinatorial components screening . herbal medicines
ABBREVIATIONSBECCs Bioactive equivalent combinatorial components CCK-8 Cell counting kit-8CK-MB Creatine kinase-MBCP Cardiotonic PillHUVEC Human umbilical vein endothelial cellIL-6 Interleukin-6LAD Left anterior descendingLDH Lactate dehydrogenaseLPS LipopolysaccharideLV Left ventricularLVEDP Left ventricular end diastolic pressureLVSP Left ventricular systolic pressureMI Myocardial infarctionMRCs Mixture of reference compoundsOx-LDL Oxidized low density lipoproteinPGE2 Prostaglandin E2PLS-DA Partial least square-discriminant analysisROS Reactive oxygen speciesSD Standard deviationSI Simulated ischemiaTNF- Tumor necrosis factor-
TTC Triphenyltetrazolium chloride
INTRODUCTION
Herbal medicines...