The problem of drug-resistant bacterial infections has reached epidemic proportions. Methicillin-resistant Staphyolcoccus aureus (MRSA) infections now kill more US citizens each year than does AIDS, and new strategies to treat or prevent such infections are greatly needed. This issue is compounded by a lack of new drug candidates in the pipeline, and the fact that bacteria very quickly develop resistance to new antibiotics. With this project, we propose to explore an alternative strategy for combating bacterial infections, the use of a botanical medicine containing multiple different compounds with diverse modes of action. The botanical under investigation is goldenseal (Hydrastis canadensis), which has been used in traditional and modern alternative medicine to treat infections. Goldenseal is a significant topic of study because of its popularity as a dietary supplement (among the top 15 best-selling botanical medicines in the US, and the 6th most commonly used by children). This plant or its constituents have demonstrated antimicrobial activity in numerous in vitro and several in vivo studies. Our strong preliminary data provide new insights into the mechanisms by which goldenseal acts against bacteria. We have shown that this plant contains a diverse array of bioactive constituents, which can act as direct antimicrobia agents, as efflux pump inhibitors, and as anti-virulence compounds (via quorum quenching). A major goal of this application is to identify the constituents that contribute to these diverse activities. To accomplish this, we will employ an innovative approach, synergy-directed fractionation, which has recently been developed and published by the principal investigator's laboratory. Our long term objective is to use the information provided by these studies to enable the preparation of topical goldenseal preparations with optimal efficacy for the treatment or prevention of bacterial infections. More broadly, we also seek to explore one of the major guiding principles of complementary and alternative medicine, that the activity of multi-component therapies can be enhanced due to synergistic interactions. The methods validated as a part of this study are expected to prove useful to other investigators who must account for the synergistic interactions that play a role in the activity of many botanical medicines.

Public Health Relevance

The proposed research is relevant to public health because it concerns a botanical dietary supplement goldenseal (Hydrastis canadensis), which is widely used but poorly understood. Goldenseal shows promise as a treatment or preventative for bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA), which are a critical health care crisis in the US. Approximately 94,000 cases of MRSA are estimated to have occurred in the US in 2005, 20% of which were fatal.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAT1)
Program Officer
Hopp, Craig
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Greensboro
Schools of Arts and Sciences
United States
Zip Code
Caesar, Lindsay K; Kellogg, Joshua J; Kvalheim, Olav M et al. (2018) Integration of Biochemometrics and Molecular Networking to Identify Antimicrobials in Angelica keiskei. Planta Med 84:721-728
Caesar, Lindsay K; Kvalheim, Olav M; Cech, Nadja B (2018) Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics. Anal Chim Acta 1021:69-77
Britton, Emily R; Kellogg, Joshua J; Kvalheim, Olav M et al. (2018) Biochemometrics to Identify Synergists and Additives from Botanical Medicines: A Case Study with Hydrastis canadensis (Goldenseal). J Nat Prod 81:484-493
Todd, Daniel A; Parlet, Corey P; Crosby, Heidi A et al. (2017) Signal Biosynthesis Inhibition with Ambuic Acid as a Strategy To Target Antibiotic-Resistant Infections. Antimicrob Agents Chemother 61:
Leyte-Lugo, Martha; Britton, Emily R; Foil, Daniel H et al. (2017) Secondary Metabolites from the Leaves of the Medicinal Plant Goldenseal (Hydrastis canadensis). Phytochem Lett 20:54-60
Egan, Joseph M; Kaur, Amninder; Raja, Huzefa A et al. (2016) Antimicrobial fungal endophytes from the botanical medicine goldenseal (Hydrastis canadensis). Phytochem Lett 17:219-225
Kellogg, Joshua J; Todd, Daniel A; Egan, Joseph M et al. (2016) Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds. J Nat Prod 79:376-86
Todd, Daniel A; Zich, David B; Ettefagh, Keivan A et al. (2016) Hybrid Quadrupole-Orbitrap mass spectrometry for quantitative measurement of quorum sensing inhibition. J Microbiol Methods 127:89-94
Bussey 3rd, Robert O; Kaur, Amninder; Todd, Daniel A et al. (2015) Comparison of the chemistry and diversity of endophytes isolated from wild-harvested and greenhouse-cultivated yerba mansa (Anemopsis californica). Phytochem Lett 11:202-208
Britton, Emily R; Ibberson, Carolyn B; Horswill, Alexander R et al. (2015) A new mass spectrometry based bioassay for the direct assessment of hyaluronidase activity and inhibition. J Microbiol Methods 119:163-7

Showing the most recent 10 out of 14 publications