Hypericin - The Facts About a Controversial Agent

Abstract

Hypericin is a naturally occurring substance found in the common St. John's Wort (Hypericum species) and can also be synthesized from the anthraquinone derivative emodin. As the main component of Hypericum perforatum, it has traditionally been used throughout the history of folk medicine. In the last three decades, hypericin has also become the subject of intensive biochemical research and is proving to be a multifunctional agent in drug and medicinal applications. Recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected. Also in the relatively newly established fields of medical photochemistry and photobiology, intensive research reveals hypericin to be a promising novel therapeutic and diagnostic agent in treatment and detection of cancer (photodynamic activation of free radical production). Hypericin is not new to the research community, but it is achieving a new and promising status as an effective agent in medical diagnostic and therapeutic applications. New, although controversial data, over the recent years dictate further research, re-evaluation and discussion of this substance. Our up-to-date summary of hypericin, its activities and potentials, is aimed to contribute to this process.

Evaluation of the Light-Sensitive Cytotoxicity of Hypericum perforatum Extracts, Fractions, and Pure Compounds

“…Quantification of several chemicals within the extracts revealed similar amounts of the identified chemicals in all ethanol extracts but no detectable amounts within the chloroform or hexane extracts (Tables 1-3). Therefore, Hp extracts containing the light-sensitive hypericin and pseudohypericin compounds were expected to exhibit greater cytotoxicity after light exposure than in the dark due to their production of singlet oxygen following photoexcitation (12,(26)(27)(28)(29). Despite containing between 1.8 and 3.7 μM hypericin and between 0.6 and 5.2 μM pseudohypericin (these concentrations are 1% of the quantities listed in Tables 2 and 3, representative of the amount of the extract stock solutions added to the cells at 1% of the treatment media), significant light-sensitive toxicity was generally only observed in the ethanol (-chloroform) and ethanol(-hexane) extracts prepared from the Frontier Herb material (Table 4) and with one ethanol extract prepared from the NCRPIS material (Table 7).…”

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

“…The phototoxicity of hypericin has been shown to be dose-and light-dependent in various cell culture studies, inducing apoptosis at lower concentrations of hypericin and light energy, whereas higher concentrations tend to induce necrotic cell death [4,12,16]. The threshold concentration of hypericin and/or light energy required to induce apoptotic versus necrotic cell death in cultured cells seems to be dependent upon several factors, including pre-incubation time before irradiation, treatment in cell culture media versus PBS or DMSO and the type of cell line [4,17,29,31,32].…”

“…Aggressive analysis of this plant over the last three decades has revealed that it possesses several biological properties, including antidepressant, antiviral and antiproliferative activities [4][5][6][7][8]. Although H. perforatum (Hp) is most commonly used as an alternative to standard tricyclic antidepressants, other biological properties possessed by this plant have also been utilized for the treatment of cancer and viral infections [8][9][10][11][12]. Widespread use of Hp as an alternative medicine has raised concern regarding its safe use by the public [1,2].…”

“…The hypericin compounds produce a significant amount of reactive oxygen species upon photoactivation, which can cause damage to areas of the body exposed to light [12,14,15]. Due to the lipophilic nature of hypericin, it has been found to preferentially accumulate in cellular membranes as well as organelles, such as liposomes, endoplasmic reticulum, and the Golgi apparatus [16,17].…”

Aspectos botânicos, químicos, farmacológicos e terapêuticos do Hypericum perforatum L.

“…Apesar de a hipericina ser considerada o composto responsável pelas atividades antidepressiva (Greeson, 2001), antiviral e antitumoral de HP (Miskovsky, 2002;Kubin et al, 2005), é, possivelmente, o mais poderoso fotossensibilizante natural já descrito (Miskovsky, 2002;Karioti & Bilia, 2010). A ingestão de grandes quantidades da planta por animais demonstrou causar uma condição de severa sensibilidade à luz, conhecida como síndrome do hipericismo (Patočka, 2003).…”