Synergy-Directed Fractionation of Botanical Medicines: A Case Study with Goldenseal (Hydrastis canadensis)

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Robert E. Cannon, Professor and Associate Head (Creator)
Nadja B. Cech, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Tyler Graf, Research Scientist (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Scott J. Richter, Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: It is often argued that the efficacy of herbal medicines is a result of the combined action of multiple constituents that work synergistically or additively. Determining the bioactive constituents in these mixtures poses a significant challenge. We have developed an approach to address this challenge, synergy-directed fractionation, which combines comprehensive mass spectrometry profiling with synergy assays and natural products isolation. The applicability of synergy-directed fractionation was demonstrated using the botanical medicine goldenseal (Hydrastis canadensis) as a case study. Three synergists from goldenseal were identified, sideroxylin (1), 8-desmethyl-sideroxylin (2), and 6-desmethyl-sideroxylin (3). These flavonoids synergistically enhance the antimicrobial activity of the alkaloid berberine (also a constituent of H. canadensis) against Staphylococcus aureus by inhibition of the NorA multidrug resistance pump. The flavonoids possess no inherent antimicrobial activity against S. aureus; therefore, they could have been missed using traditional bioactivity-directed fractionation. The flavonoid synergists are present at higher concentration in extracts from H. canadensis leaves, while the antimicrobial alkaloid berberine is present at higher levels in H. canadensis roots. Thus, it may be possible to produce an extract with optimal activity against S. aureus using a combination of goldenseal roots and leaves.

Additional Information

Journal of Natural Products, 2011, 74, 1621-1629
Language: English
Date: 2011
herbal medicines, Hydrastis Canadensis, Staphylococcus aureus, synergy-directed fractionation

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