Abstract
PurposeTo 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.MethodsWe 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.ResultsA 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-013-1283-1) contains supplementary material, which is available to authorized users.
Highlights
Herbal medicines have played an important role in health maintenance and disease treatment for thousands of years [1,2]
While the nature of this study refers to Cardiotonic Pill, we suggest that this screening method is promising for detecting bioactive equivalent combinatorial components (BECCs) for other herbal medicines, and more importantly, to improve quality control of herbal medicines and inspire an herbal medicines based discovery of combinatorial therapeutics
Structural characterization was performed by Q-TOF mass spectrometry (MS), and the total ion chromatograms of Cardiotonic Pill (CP) in positive and negative ion modes were shown in Figure S3, Supplementary Material
Summary
Herbal medicines have played an important role in health maintenance and disease treatment for thousands of years [1,2]. A variety of research efforts in recent decades have been focused on isolating and identifying single effective constituents from herbal medicines. They disregarded the combinatorial role and integrative therapeutic effects of multiple active compounds [8,9]. The therapeutic efficacy of herbal medicines is achieved by combinatorial components rather than single compound. It is incumbent upon researchers to elucidate the exact combinatorial composition of effective components in herbal medicines, if any, accounting for of the holistic efficacy of herbal medicines
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