Secondary metabolites from the leaves of the medicinal plant goldenseal ( Hydrastis canadensis )

Abstract

The study presented herein constitutes an extensive investigation of constituents in Hydrastis canadensis L. (Ranunculaceae) leaves. It describes the isolation and identification of two previously unknown compounds, 3,4-dimethoxy-2-(methoxycarbonyl)benzoic acid (1) and 3,5,3′-trihydroxy-7,4′-dimethoxy-6,8-C-dimethyl-flavone (2), along with the known compounds (±)-chilenine (3), (2R)-5,4′-dihydroxy-6-C-methyl-7-methoxy-flavanone (4), 5,4′-dihydroxy-6,8-di-C-methyl-7-methoxy-flavanone (5), noroxyhydrastinine (6), oxyhydrastinine (7) and 4′,5′-dimethoxy-4-methyl-3′-oxo-(1,2,5,6-tetrahydro-4H-1,3-dioxolo-[4′,5′:4,5]-benzo[1,2-e]-1,2-oxazocin)-2-spiro-1′-phtalan (8). Compounds 3-8 have been reported from other sources, but this is the first report of their presence in H. canadensis extracts. A mass spectrometry based assay was employed to demonstrate bacterial efflux pump inhibitory activity against Staphylococcus aureus for 2, with an IC50 value of 180 ± 6 μM. This activity in addition to that of other bioactive compounds such as flavonoids and alkaloids, may explain the purported efficacy of H. canadensis for treatment of bacterial infections. Finally, this report includes high mass accuracy fragmentation spectra for all compounds investigated herein which were uploaded into the Global Natural Products Social molecular networking library and can be used to facilitate their future identification in H. canadensis or other botanicals.

Biochemometrics to Identify Synergists and Additives from Botanical Medicines: A Case Study with Hydrastis canadensis (Goldenseal)

“…Chilenine has previously been reported as a constituent of H. canadensis , but its biological activity is unknown. 21 The data presented here suggest that it might possess antimicrobial activity (alone or in combination with berberine), a possibility that could be investigated in a future study.…”

“…Compounds 1 – 3 and 5 are known efflux pump inhibitors, as demonstrated in several previous studies. 5,21 Compound 8 has not previously been evaluated for biological activity against S. aureus , but has been shown to have antimicrobial activity against Streptococcus mutans and Fusobacterium nucleatum . 22 Based upon its structural similarity to 1 , which has one less hydroxy group at the C-3′ position, 8 is likely to be active as an efflux pump inhibitor.…”

“…As a side note, alkaloid 23 was found to be a product of β -hydrastine- N -oxide under reflux conditions and is likely present here as an isolation artifact. 21,42 …”

“…21 H. canadensis also contains several alkaloids that do not act as efflux pump inhibitors ( 13 , 17 , 24 ) or possess biologically relevant antimicrobial activity ( 10 , 13 – 15 , 17 , 24 , 25 ). 21–31 Finally, a number of compounds have also been identified from H. canadensis for which biological activity has not been evaluated ( 7 , 11 , 12 , 16 , 18 , 19 , 23 , 27 ). 21,30,32–37 Relying on existing knowledge about the chemistry and biological activity of H. canadensis , the goal with this investigation was to apply synergy-directed fractionation combined with biochemometric data analysis to an H. canadensis extract.…”

Molecular networking as a dereplication strategy for monitoring metabolites of natural product treated cancer cells

“…Conventionally, spectra of a natural product obtained by liquid chromatography–mass spectrometry, nuclear magnetic resonance and infrared spectroscopy are interpreted based on prior knowledge, or at least “postulation” to the chemical structures of the analyte compounds . Recently, a dereplication strategy utilizing Global Natural Product Social (GNPS) molecular networking has been proposed to leverage the structural features of known compounds to decrypt the tandem mass spectra of unknown compounds . Specifically, cosine similarities among each pair of tandem mass spectra of individual specialized metabolites are calculated, of which the compounds with similar chemical structures are prone to cluster together .…”