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Hypericine

Anglais : hypericin
Espagnol : hypericina
Étymologie : latin Hypericum, nom du genre dans lequel elle a été identifiée, suffixe -ine
n. f. Naphtodianthrone octacyclique, présente en faible quantité (<0,3 %) dans les feuilles et les fleurs du millepertuis (Hypericum perforatum L., Hypericaceae). Son absorption et son passage de la barrière hémato-encéphalique sont discutés et, par conséquent, son implication dans les propriétés antidépressives légères revendiquées pour le millepertuis est sujette à caution. L'hypéricine est, in vitro, antibactérienne et antivirale ; elle est aussi photosensibilisante, cette propriété étant à l'origine d'une des précautions d'emploi du millepertuis.
L'hypéricine synthétique est utilisée par voie locale, avec le statut de médicament orphelin aux États-Unis et en Europe, dans le traitement du lymphome T cutané dans le cadre d'une thérapie photodynamique.
L'accumulation préférentielle de l'hypéricine dans les cellules cancéreuses permet également son utilisation comme indicateur de ces cellules.

Curr Pharm Des. 2005;11(2):233-53. Hypericin--the facts about a controversial agent.
Kubin A1, Wierrani F, Burner U, Alth G, Grünberger W.
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.



Hypericin is an anthraquinone derivative that is naturally found in the yellow flower of Hypericum perforatum (St. John's wort) with antidepressant, potential antiviral, antineoplastic and immunostimulating activities. Hypericin appears to inhibit the neuronal uptake of serotonin, norepinephrine, dopamine, gamma-amino butyric acid (GABA) and L-glutamate, which may contribute to its antidepressant effect. Hypericin may also prevent the replication of encapsulated viruses probably due to inhibition of the assembly and shedding of virus particles in infected cells. This agent also exerts potent phototoxic effects by triggering apoptotic signaling that results in formation of reactive oxygen species.

Hypericin is found in alcoholic beverages. Hypericin is widespread in Hypericum species especially Hypericum perforatum (St John's Wort) Hypericin is a red-coloured anthraquinone-derivative, which, together with hyperforin, is one of the principal active constituents of Hypericum (Saint John's wort). Hypericin is believed to act as an antibiotic and non-specific kinase inhibitor. Hypericin may inhibit the action of the enzyme dopamine -hydroxylase, leading to increased dopamine levels, although thus possibly decreasing norepinephrine and epinephrine. Hypericin has been shown to exhibit anti-rheumatic, anti-depressant and anti-viral functions (PMID: 11458458, 12770617, 9796444). Hypericin belongs to the family of Triphenylenes. These are compounds containing a triphenylene moiety, which consists of four fused benzene rings forming a 9, 10-benzo[l]phenanthrene.


Free Radic Res. 2007 Feb;41(2):234-41.
The main components of St John's Wort inhibit low-density lipoprotein atherogenic modification: a beneficial "side effect" of an OTC antidepressant drug?
Laggner H1, Schreier S, Hermann M, Exner M, Mühl A, Gmeiner BM, Kapiotis S.
Hypericin and pseudohypericin are polycyclic-phenolic structurally related compounds found in Hypericum perforatum L. (St John's wort). As hypericin has been found to bind to LDL one may assume that it can act as antioxidant of LDL lipid oxidation, a property which is of prophylactic/therapeutic interest regarding atherogenesis as LDL oxidation may play a pivotal role in the onset of atherosclerosis. Therefore, in the present paper hypericin, pseudohypericin and hyperforin, an other structurally unrelated constituent in St John's wort were tested in their ability to inhibit LDL oxidation. LDL was isolated by ultracentrifugation and oxidation was initiated either by transition metal ions (copper), tyrosyl radical (myeloperoxidase/hydrogen peroxide/tyrosine) or by endothelial cells (HUVEC). LDL modification was monitored by conjugated diene and malondialdehyde formation. The data show that all compounds (hypericin, pseudohypericin and hyperforin) at doses as low as 2.5 micromol/l are potent antioxidants in the LDL oxidation systems used. The results indicate that the derivatives found in Hypericum perforatum have possible antiatherogenic potential.


Front. Plant Sci., 06 May 2016 | https://doi.org/10.3389/fpls.2016.00560
Hypericin in the Light and in the Dark: Two Sides of the Same Coin
Hypericin (4,5,7,4′,5′,7′-hexahydroxy-2,2′-dimethylnaphtodiant hrone) is a naturally occurring compound synthesized by some species of the genus Hypericum
Hypericin was first isolated from Hypericum perforatum L. (Brockmann et al., 1939), commonly known as St. John's wort, which is one of the best characterized and most important representatives of this genus, because of its broad pharmacological activity (antidepressant, antimicrobial, anticancer, anti-inflammatory, wound healing, etc.) (reviewed in Kasper et al., 2010; Wölfle et al., 2014). Hypericin and its derivatives are accumulated in special morphological structures, so called dark nodules, occurring in the aerial parts of hypericin-producing Hypericum species. The newest data on interspecific variation in localization of hypericins and spatial chemo-profiling of hypericin in some Hypericum species were published recently (Kusari et al., 2015; Kucharikova et al., 2016).

In addition to St. John's wort, this secondary metabolite was found in several other Hypericum species (Kitanov, 2001; Ayan et al., 2004) and in some basidiomycetes (Dermocybe spp.) (Dewick, 2002; Garnica et al., 2003) or endophytic fungi growing in Hypericum perforatum (Thielavia subthermophila) (Kusari et al., 2008, 2009). As hypericin is a bioactive compound that is applicable in several medicinal approaches, its content has been evaluated in in vitro grown Hypericum perforatum and in its transgenic clones (Čellárová et al., 1997; Košuth et al., 2003; Koperdáková et al., 2009), or in Hypericum cultures exposed to various biotechnological applications that focused on their preservation or stimulation of secondary metabolite production (Urbanová et al., 2006; Bruňáková et al., 2015; reviewed in: Čellárová, 2011).

Hypericin is well-known as a potent natural photosensitizing agent with great potential in anticancer photodynamic therapy (PDT) and photodynamic diagnosis (PDD). Besides its antineoplastic action, light-dependent in vitro fungicidal (Rezusta et al., 2012; Paz-Cristobal et al., 2014) and bactericidal effects (Kashef et al., 2013; García et al., 2015) have also been reported. In addition, light-activated hypericin is considered to be an effective antiviral agent (Hudson et al., 1993; Prince et al., 2000). However, some clinical studies have revealed that high doses of hypericin can induce phototoxic skin reactions without showing any detectable antiviral or antiretroviral activity in patients with viral infections (Gulick et al., 1999; Jacobson et al., 2001). The controversy concerning the virucidal effect of hypericin was summarized in detail by Kubin et al. (2005).

However, the potential use of this secondary metabolite in medicine might be broader than currently thought. Although hypericin has been extensively studied mainly because of its photodynamic and photocytotoxic properties, it also possesses various positive or negative biological activities without being activated by light.

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