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Title: THE PRODUCTION OF HYPERICINS AND HYPERFORIN BY IN VITRO CULTURES OF HYPERICUM PERFORATUM

Author
item KIRAKOSYAN, ARA - YEREVAN STATE UNIV
item SIRVENT, TARA - BOYCE THOMPSON INST
item Gibson, Donna
item KAUFMAN, PETER - UNIVERSITY OF MICHIGAN

Submitted to: Biotech and Applied Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/2003
Publication Date: 11/15/2003
Citation: Kirakosyan, A., Sirvent, T., Gibson, D.M., Kaufman, P. 2003. The production of hypericins and hyperforin by in vitro cultures of hypericum perforatum. Biotech and Applied Biochemistry. 39:71-81.

Interpretive Summary: Hypericum perforatum L. (family Hypericaceae), commonly called St. John's wort, is considered to be an important dietary supplement, with worldwide sales of over $500 million. St. John's wort is supplied from cultivated as well as wild-harvested materials, generating concerns for loss of biodiversity, variability in quality, and adulteration and contamination issues. We were invited to summarize the status of production using plant cell culture system to generate the biologically active components in St. John's wort. This review summarizes our work, as well as a number of other laboratories, that are investigating the biochemical pathways involved and the various methods that can be used to optimize the production of the biologically active compounds in St. John's wort.

Technical Abstract: St. John's wort is an herbaceous perennial distributed throughout the world that has been widely used in traditional medicine. The plant produces several types of biologically active compounds, including the hypericins - a family of light-activated anthraquinones, localized within specialized glands found predominantly on flowers and leaves - and the hyperforins - a family of prenylated acylphloroglucinols localized in the reproductive structures of the plant. Hypericins are known to be toxic to mammals and display anti-viral and anti-cancer activity, but the role of these compounds within the plant is unknown. Hyperforins display potent anti-microbial activity and are thought to be the primary bioactive ingredient for anti-depressive effects of the herb. Introduction of St. John's wort from Europe into the United States occurred in the last century. Since the plant is considered a noxious weed, few efforts have been carried out to analyze populations in the context of secondary metabolite concentrations. But in terms of secondary metabolite studies, Hypericum perforatum (St. John's wort) is an ideal model system to study the biosyntheses of aromatic polyketides and regulation of those pathways by environmental and genetic influences. This is due, in part, to the ease of conducting these studies in plant tissue culture. This review describes the progress of secondary metabolite studies currently underway in H. perforatum. Specifically, this review focuses on the production and regulation of the hypericins and the hyperforins in wild populations, field cultivation, greenhouse studies, and plant tissue culture. Additionally, factors optimizing compound production - particularly in cell culture - are presented and reviewed.