Phytochemical Diversity in Hypericum (St. John´s Wort)

The flowering plant genus Hypericum (Clusiaceae) is represented by ca. 450 species, the most well-known of which is H. perforatum L. (Common St. John`s Wort). This economically-valuable medicinal plant has a long history of use, and extracts are currently sold in Europe and North America to treat mild and moderate depression. The extracts contain many medicinally active constituents, including flavonoid glycosides, naphthodianthrones (e.g. hypericin and pseudohypericin), and acylphloroglucinol derivatives (e.g. hyperforin). Consequently, the identification of genetic and/or environmental factors affecting production of these compounds is of considerable interest to many groups, particularly plant breeders and pharmaceutical companies. Goal One of the project examines the influence of reproductive biology and genetic diversity on phytochemical variation in Hypericum perforatum. In this species, seeds can be produced either sexually or asexually, resulting in many levels of genetic variation in mature plants. While metabolic variation among species within a genus, populations within a species, and even plants within a population is commonly observed, few attempts have been made to study the specific influence of genetic factors on such variation in a medicinal plant species under controlled conditions. Currently, a rare opportunity exists to perform exactly such a study through access to an extensive collection of H. perforatum plants, for which reproductive strategies and genetic diversity levels are known and which represent over 150 European and North American populations, growing in greenhouses at the Leibniz Institut für Pflanzengenetik und Kulturpflanzenforschung (Gatersleben, Germany). As part of Goal One of the proposal, we would like to conduct metabolic profiling of this unique collection of H. perforatum plants. Goal Two outlines plans to search for new medicinally valuable secondary metabolites, particularly acylphloroglucinol derivatives, in Hypericum and explores the influences of ecological pressures on the production of these compounds in targeted species. Recent research performed through funding of a Lise Meitner Postdoctoral Grant (FWF M844-B05) allowed the isolation and identification of several compounds with promising bioactivities against the honeybee pathogens Ascosphaera apis and Paenibacillus larvae, as well as against the GABA receptor and the 5-LOX enzyme, important in human diseases. As part of Goal Two of the proposal, we plan to (I) continue bioassay-guided isolation of structurally-related acylphloroglucinol derivatives to discover new medicinal lead compounds, (II) establish and maintain two bee pathogenic microorganism bioassays at Karl-Franzens-University for extract and compound screening, (III) conduct chemical modification of previously isolated bioactive compounds in order to elucidate structure-activity relationships, and (IV) examine variation in inducible chemical defense responses by exposing several species of Hypericum to herbivory pressures and/or chemical elicitation.