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European Journal of Pharmaceutics and Biopharmaceutics
Vol. 12
6, 2018, Pages: 10-26

Biotechnological production of hyperforin for pharmaceutical formulation

Mariam Gaid, Eline Biedermann, Jendrik Füller, Paul Haas, Sönke Behrends, Rainer Krull, Stephan Scholl, Ute Wittstock, Christel Müller-Goymann, Ludger Beerhues

Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Germany.


Hyperforin is a major active constituent of Hypericum perforatum (St. John’s wort). It has amazing pharmacological activities, such as antidepressant properties, but it is labile and difficult to synthesize. Its sensitivity and lipophilicity are challenges for processing and formulation. Its chemical complexity provokes approaches of biotechnological production and modification. Dedifferentiated H. perforatum cell cultures lack appropriate storage sites and hence appreciable hyperforin levels. Shoot cultures are capable of forming hyperforin but less suitable for biomass up-scaling in bioreactors. Roots commonly lack hyperforin but a recently established adventitious root line has been demonstrated to produce hyperforin and derivatives at promising levels. The roots also contained lupulones, the typical constituents of hop (Humulus lupulus). Although shear-sensitive, these root cultures provide a potential production platform for both individual compounds and extracts with novel combinations of constituents and pharmacological activities. Besides in vitro cultivation techniques, the reconstruction of hyperforin biosynthesis in microorganisms is a promising alternative for biotechnological production. The biosynthetic pathway is under study, with omics-technologies being increasingly implemented. These biotechnological approaches may not only yield hyperforin at reasonable productivity but also allow for modifications of its chemical structure and pharmacological profile.

Graphical abstract

Keywords: Hypericum perforatum, Hyperforin, Formulations, Stabilization, Pharmacological profile, In vitro cultures, Root cultures, Gene identification, Heterologous production, Hypericin.

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