USING METABOLOMICS TO INVESTIGATE NATIVE AMERICAN MEDICINAL PLANTS AND THEIR USES

Korey J. Brownstein

To relieve pain and inflammation, the people of southern Africa, Europe, and North America use the tubers of Harpagophytum procumbens. However, the use of H. procumbens is an unsustainable practice because cultivation lags behind the demand rate. The seeds have a low germination rate and the plants require years to mature. The candidate metabolite responsible for the anti-inflammatory properties of H. procumbens may be harpagoside; however, it has been shown that extracts of H. procumbens tubers are more active in bioassays than harpagoside alone. Tuber extracts have also been shown to possess anti-inflammatory properties in human clinical trials. It is apparent that instead of relying on a single metabolite, the entire metabolite profile should be investigated. My research involves the rediscovery of North American plants with similar metabolite profiles as H. procumbens. I have shown that Scrophularia californica, S. lanceolata, and S. marilandica produce not only abundant amounts of harpagoside, but also other metabolites previously characterized in H. procumbens. A field trial of S. lanceolata and S. marilandica also revealed the optimal production of metabolites with important pharmacological properties. Using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) in combination with metabolomics software enabled us to identify differences and similarities between the metabolite profiles of each Scrophularia species and characterize metabolites with potential bioactivity. The capabilities of UPLC-MS were then used to analyze residue extracted from ancient artifacts. Previous methods in residue analysis relied on several biomarkers (i.e., anabasine, cotinine, and nicotine) to determine the prehistoric use of pipes. This approach has limitations because these biomarkers are common throughout the plant kingdom. Therefore, a method for ancient residue analysis was developed to analyze a greater suite of species-specific biomarkers. Experimental pipes smoked with fifteen common smoke plants as well as an ancient pipe were extracted using a sequential extraction method. The experimental and ancient pipe extracts were analyzed by UPLC-MS and compared using a novel metabolomics method. The ancient pipe contained nicotine, but our methods scaled-up the number of species-specific biomarkers revealing that this pipe may have been smoked with a mixture of plants native to North America, including an endemic tobacco.

USING METABOLOMICS TO INVESTIGATE NATIVE AMERICAN MEDICINAL PLANTS AND THEIR USES

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