"Amyloid and Amino Acid Assembly: Ion Mobility, Atomic Force Microscopy and Infrared Spectroscopy Approaches"
Professor Michael Bowers, UC Santa Barbara
"Biochemometrics: An Untargeted Approach for Identifying Bioactives in Botanical Medicines"
Emily Britton, Laboratory of Professor Nadja Cech, UNC Greensboro, Department of Chemistry
Botanical medicines are highly complex, and their biological activity is often due to multiple constituents that work together additively or synergistically. One strategy for identifying synergists and overcoming the bias inherent to bioassay-guided fractionation is to utilize an untargeted biochemometrics-guided fractionation approach. Biochemometrics, which is the combination of metabolomics data and biological measurements using multivariate statistical approaches to predict active constituents, serves as an improvement upon existing techniques. The result of this methodology is selectivity ratio (SR) plots that represent retention time-mass pairs with varying degrees of correlation to the biological activity being evaluated. As a case study, we sought to employ this approach to identify synergists in the medicinal plant Hydrastis canadensis, which is known to contain multiple flavonoids that potentiate the activity of the antimicrobial alkaloid berberine against Staphylococcus aureus. After three stages of fractionation, LC-MS analysis and antimicrobial screening, ions representing known synergists were identified as correlating with bioactivity. Additionally, a new flavonoid, 3,3´-dihydroxy- 5,7,4´trimethoxy- 6,8-C-dimethylflavone, was predicted via biochemometrics and confirmed to potentiate the activity of berberine. This study demonstrates the importance of fractionation when using metabolomics for identifying bioactive components from botanical medicines, along with the strength of SR plots in guiding isolation efforts.