New Method Pinpoints Synergistic Botanical Compounds

Richard A. Cech

ANTIMICROBIAL HERB Americans spend about $5 billion annually on natural medicines, such as those extracted from the goldenseal plant.

Botanical dietary supplements and medicines make up a multi-billion-dollar industry in the U.S., but scientists have had trouble proving their efficacy. Many supporters say these treatments succeed because of a phenomenon called synergy, in which many molecules together produce a combined medicinal effect more powerful than a sum of the effects of individual compounds. Now scientists have developed a method to identify synergistic compounds in botanicals (J. Nat. Prod., DOI: 10.1021/np200336g).

Goldenseal (Hydrastis canadensis) is a perennial herb in the buttercup family that is widely used to treat infections. Previous studies have shown that it has antibacterial activity, but scientists have yet to pinpoint all of its molecules that kill bacteria.   

Scientists knew of one alkaloid in goldenseal called berberine that has weak antimicrobial activity. Nadja Cech at the University of North Carolina, Greensboro, and her colleagues wanted to find the synergistic compounds in this herb that helped berberine kill the bacterium Staphylococcus aureus.

The team developed a process they named “synergy directed fractionation” to isolate compounds that boosted berberine’s effectiveness. They first used flash chromatography and high-performance liquid chromatography to separate an extract of goldenseal leaves into fractions. They identified the molecules present in each fraction with electrospray ionization mass spectrometry. The researchers then added berberine to each fraction and tested whether the mixture killed S. aureus bacteria at greater rates than berberine did alone. They repeated the process until they narrowed the fractions down to three synergistic compounds called sideroxylin, 8-desmethyl-sideroxylin, and 6-desmethyl-sideroxylin.  

Cech says that her study develops “a very careful, strategic approach that takes the guesswork out of identifying the synergistic compounds.” She hopes to use the method to study other botanicals and, eventually, to develop drugs to treat antibiotic-resistant infections.

J. Nat. Prod.

sideroxylin (1), 8-desmethyl-sideroxylin (2), and 6-desmethyl-sideroxylin (3), and berberine (4)

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