Quorum Quenching and Antimicrobial Activity of Goldenseal (Hydrastis canadensis) against Methicillin-Resistant Staphylococcus aureus (MRSA)

Abstract

The popular herbal remedy goldenseal (Hydrastis canadensis L.) is traditionally used to treat skin infections. With this study, we show activity of H. canadensis extracts in vitro against methicillin-resistant Staphylococcus aureus (MRSA). An extract from H. canadensis leaves demonstrated more potent antimicrobial activity than the alkaloid berberine alone (MICs of 75 µg/mL and 150 µg/mL, respectively). LC-MS detected alkaloids and efflux-pump inhibitory flavonoids in the extract, and the latter may explain the enhanced efficacy of the extract compared to berberine alone. We also show evidence of anti-virulence activity as a second mechanism by which H. canadensis acts against S. aureus. The H. canadensis leaf extract (but not the isolated alkaloids berberine, hydrastine, and canadine) demonstrated quorum quenching activity against several clinically relevant MRSA isolates (USA300 strains). Our data suggest that this occurs by attenuation of signal transduction through the AgrCA two-component system. Consistent with this observation, the extract inhibited toxin production by MRSA, and prevented damage by MRSA to keratinocyte cells in vitro. Collectively, our results show that H. canadensis leaf extracts possess a mixture of constituents that act against MRSA via several different mechanisms. These findings lend support for the traditional application of crude H. canadensis extracts in the treatment of prevention of infection.

ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

“…Despite clearly representing a wealth of bioactive molecules, natural products have received limited attention with respect to identifying specific inhibitors of S. aureus QS that are not bactericidal. To date, other natural products identified as agr inhibitors include (i) ␣-cyperone from the nut grass plant Cyperus rotundus (93), (ii) the fungal metabolite ambuic acid (94), and extracts from (iii) the goldenseal plant Hydrastis canadensis (95) and (iv) three Italian medicinal plants, Ballota nigra, Castanea sativa, and Sambucus ebulus (96).…”

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

“…A recent investigation found that extracts of goldenseal were able to inhibit the Agr signaling pathway of S. aureus, as determined by luciferase reporters that indicate quorum-sensing activity, and were shown to reduce alpha-toxin production (280). Application of the extracts to cultures of methicillin-resistant S. aureus (MRSA) grown with keratinocytes reduced keratinocyte toxicity incurred by the bacteria.…”

“…Application of the extracts to cultures of methicillin-resistant S. aureus (MRSA) grown with keratinocytes reduced keratinocyte toxicity incurred by the bacteria. Interestingly, the extracts were active against three of the four agr groups, indicating the active component has a generalized mechanism of inhibition against the signaling pathway (280). In addition to the benefits that a broad Agr inhibitor would provide as a therapeutic, the compound(s), once identified, will serve as a valuable molecular probe to help understand signal transduction of the Agr pathway.…”

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

“…Arrows represent the region of the chromatogram in which a given ion corresponding to a known constituent of H. canadensis (indicated by compound numbers) could be detected. Compounds 1 – 7 , 10 , 13 , 16 , 17 , 20 – 24 , and 28 were identified by comparison of retention time and fragmentation with authenticated standards, 20 while compounds 8 , 9 , 11 , 12 , 14 , 15 , 18 , 19 , and 25 – 27 were tentatively identified by comparison of accurate mass and molecular formula with literature reports. 22,24,27,29,33,36,37 29 is a new flavonoid that was isolated and identified based on NMR and MS data as part of this report.…”

“…18,19 Activity against the common Gram-positive bacterium Staphylococcus aureus was evaluated, given that H. canadensis has previously been shown to possess activity against this pathogen. 20 …”