Abstract
BackgroundPattern-oriented chemical profiling is increasingly being used to characterize the phytochemical composition of herbal medicines for quality control purposes. Ideally, a fingerprint of the biological effects should complement the chemical fingerprint. For ethical and practical reasons it is not possible to test each herbal extract in laboratory animals or humans. What is needed is a test system consisting of an organism with relevant biology and complexity that can serve as a surrogate in vitro system. The purpose of this study was to test the hypothesis that the Saccharomyces cerevisiae transcriptome might be used as an indicator of phytochemical variation of closely-related yet distinctly different extracts prepared from a single species of a phytogeographically widely distributed medicinal plant. We combined phytochemical profiling using chromatographic methods (HPTLC, HPLC-PDA-MS/MS) and gene expression studies using Affymetrix Yeast 2.0 gene chip with principal component analysis and k-nearest neighbor clustering analysis to test this hypothesis using extracts prepared from the phytogeographically widely distributed medicinal plant Equisetum arvense as a test case.ResultsWe found that the Equisetum arvense extracts exhibited qualitative and quantitative differences in their phytochemical composition grouped along their phytogeographical origin. Exposure of yeast to the extracts led to changes in gene expression that reflected both the similarities and differences in the phytochemical composition of the extracts. The Equisetum arvense extracts elicited changes in the expression of genes involved in mRNA translation, drug transport, metabolism of energy reserves, phospholipid metabolism, and the cellular stress response.ConclusionsOur data show that functional genomics in S. cerevisiae may be developed as a sensitive bioassay for the scientific investigation of the interplay between phytochemical composition and transcriptional effects of complex mixtures of chemical compounds. S. cerevisiae transcriptomics may also be developed for testing of mixtures of conventional drugs (“polypills”) to discover novel antagonistic or synergistic effects of those drug combinations.
Highlights
Pattern-oriented chemical profiling is increasingly being used to characterize the phytochemical composition of herbal medicines for quality control purposes
Herbal medicine, which can rightfully be considered a progenitor of modern pharmacotherapy, has along the way been relegated to the sidelines and its continued popularity with the general public is viewed by many orthodox medical professionals at best as a useless but harmless anachronism that can be harnessed for its placebo effects or at worst as a harmful superstition with potentially lethal adverse effects that needs to be discouraged [8,9]
Chromatograms generated using high performance liquid chromatography (HPLC) and detection using a photodiode array (PDA) set at 280 nm contained 35 ± 7 peaks, triple the number of constituents contained in the high performance thin-layer chromatography (HPTLC) profile (Figure 1B)
Summary
Pattern-oriented chemical profiling is increasingly being used to characterize the phytochemical composition of herbal medicines for quality control purposes. The notion that therapeutic effects of herbal medicines were due to the presence of a distillable “quintessence” popularized by Paracelsus and fellow alchemists some 450 years ago [1], morphed over time into the scientific hypothesis that pharmacological effects of herbal medicines are due to their content of plant-derived chemical compounds (mainly so called secondary metabolites) [2,3] Research based on this hypothesis conducted over the last two centuries has led to the isolation and structural elucidation of some of the best-known drugs and has led to the creation of modern pharmacology and pharmacological therapy [2,4,5,6,7]. A good drug is thought to act like Paul Ehrlich’s “magical bullet” that finds its target and in the process “destroys” the disease process [14]
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