Hypericins as Potential Leads for New Therapeutics

70 years have passed since the first isolation of the naphthodianthrones hypericin and pseudohypericin from Hypericum perforatum L. Today, they continue to be one of the most promising group of polyphenols, as they fascinate with their physical, chemical and important biological properties which derive from their unique chemical structure. Hypericins and their derivatives have been extensively studied mainly for their antitumor, antiviral and antidepressant properties. Notably, hypericin is one of the most potent naturally occurring photodynamic agents. It is able to generate the superoxide anion and a high quantum yield of singlet oxygen that are considered to be primarily responsible for its biological effects. The prooxidant photodynamic properties of hypericin have been exploited for the photodynamic therapy of cancer (PDT), as hypericin, in combination with light, very effectively induces apoptosis and/or necrosis of cancer cells. The mechanism by which these activities are expressed continues to be a main topic of discussion, but according to scientific data, different modes of action (generation of ROS & singlet oxygen species, antiangiogenesis, immune responces) and multiple molecular pathways (intrinsic/extrinsic apoptotic pathway, ERK inhibition) possibly interrelating are implicated. The aim of this review is to analyse the most recent advances (from 2005 and thereof) in the chemistry and biological activities (in vitro and in vivo) of the pure naphthodianthrones, hypericin and pseudohypericin from H. perforatum. Extracts from H. perforatum were not considered, nor pharmakokinetic or clinical data. Computerised literature searches were performed using the Medline (PubMed), ChemSciFinder and Scirus Library databases. No language restrictions were imposed

Wirkung von Hypericin-induzierter PDT auf die intrazelluläre Ca2+-Konzentration humaner Glioblastomzellen

During photodynamic therapy (PDT) the interaction between light and photosensitizers induces oxidative stress and the production of reactive oxygen species (ROS). ROS formation influences ion channels and causes changes in the Ca²+ concentration which may induce further reactions leading to cell stimulation or cell death. In this study we analysed the influence of irradiation conditions on the cell death mechanisms during Hypericin-induced PDT. The process of apoptosis is characterised by morphological and physiological changes of the cell membrane and of the whole intracellular chain reactions. The translocation of the phospholipid phosphatidylserine from the inner to the outer leaflet of the plasma membrane is one of the earliest indications of apoptotic cell death. The translocation was traced by the binding of FITC (fluorescein isothiocyanate) conjugated Annexin-V to phosphatidilserine and FACS (fluorescence activated cell sorting) analysis