Hypericin inhibitor

Zhang W, Law RE, Hinton DR, Couldwell WT. (1997). Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor. Cancer Lett. 120(1) 31-8. 

Dianthrone derivatives Hypericin, pseudohypericin, anthranol, photohypericin, hypericodehydrodianthrone Flavanols Catechin polymers (condensed tannins), leucocyanidin, epicatechin Photodynamic, antidepressant [monoamine oxidase inhibitor (MAOI)], antiviral Astringent, anti-inflammatory, styptic, antiviral... 

The hypericin fraction was initially reported to have MAO-A and -B inhibitor properties. Later studies found that the concentration required for this inhibition was higher than that achieved with recommended dosages. In vitro studies using the commercially formulated hydroalcoholic extract have shown inhibition of nerve terminal reuptake of serotonin, norepinephrine, and dopamine. While the hypericin constituent did not show reuptake inhibition for any of these systems, the hyperforin constituent did. Chronic administration of the commercial extract has also been reported to significantly down-regulate the expression of cortical 13 adrenoceptors and up-regulate the expression of serotonin receptors (5-HT2) in a rodent model. 

Binapthoquinones include the phototoxic phytotoxin cercosporin from the fungus Cercospora (two Phe Q moieties linked by two Phe—Phe links and an MD link). Hypericin (two anthraquinones linked by three Phe—Phe linkages) is a bianthraquinone from Hypericum species (Hypericaceae). Hypericin is a phototoxic protein kinase inhibitor that causes light-dependent ovine facial eczema. Benzonaphthoquinones include the der-matitic cypripedin (Phe Phe QJ. Lichen 7-chloroemodin is a novel chloroanthraquinone and the fused tricyclic pyrano-a-naphthoquinone (3-lapachone (Phe oQJ C50) is a reverse transcriptase inhibitor with antimicrobial and cytotoxic activity. 

This herb is also known as St. Joan s wort, klamath weed, and goatweed. It has historically been used for many purposes, but most recently it is marketed as an antidepressant. In fact, it outsells all conventional antidepressants in Germany. The active constituent is hypericin that seems to act as a weak monoamine oxidase MAO inhibitor and a selective serotonin reuptake inhibitor (SSRI). Dopamine and norepinephrine uptakes are also mildly inhibited. St. John s wort is available in many forms, as a tablet, tea, tincture, and the raw dried herb. For best results, a tablet standardized to contain 0.3% hypericin should be taken Kira by Lichtwer Pharma is the most extensively studied. Randomized, placebo-controlled trials using 300 mg of St. John s Wort three times daily have found it to be superior to placebo in mild to moderate depression. Response rates are generally regarded as inferior to conventional antidepressants, including... 

Saint John s wort is a serotonin reuptake inhibitor and to a lesser degree appears to inhibit monoamine oxidase. The toxin is hypericin, an anthraquinone dimer, which is present throughout the plant. It also contains tannin, rutin, and flavinoids. 

The pharmacological activities of the various constituents of St.John s wort have been studied extensively. Hyperforin appears to be the major bioactive constituent and it acts in several ways serving as a neurotransmitter reuptake inhibitor with a broad selectivity, as a ligand for the pregnane X receptor, and as an antibacterial and antitumor agent. It also has a rapid effect on amyloid precursor protein processing, indicating a possible role in the prevention of Hypericin and the flavonoid constituents may have... 

Assays with extracts devoid of hypericin but with a high content of hyperforin as well as assays with pure hyperforin demonstrated that this metabolite can modulate the function of various neurotransmitters involved in depression, being a potent inhibitor of serotonin, dopamine, noradrenaline and GABA uptake with almost equal potency. Moreover, results from clinical studies evidenced that the antidepressant efficacy of Hypericum preparations correlates with their content of hyperforin [6,87],... 

A commoniy reported drug-dietary suppiement interaction is between St. John s Wort and FiiV protease inhibitors, ieading to drug resistance and treatment faiiure. St. John s wort is a popuiar dietary suppiement often used for depression. Of the two substances found in St. John s wort, hypericin and hyperforin, hyperforin appears to be the main constituent, with in vitro seieotive serotonin reuptake inhibitor (SSRi) activity (see Chapter 21). Hyperforin aiso appears to be the more potent inducer of CYP3A enzymes based on in vitro and in vivo studies. 

Mirossay, L., Mirossay, A., Kocisova, E., Radvakova, I., Miskovsky, R, and Mojzis, J., Hypericin-induced phototoxicity of human leukemic cell line HL-60 is potentiated by omeprazole, an inhibitor of H+K+-ATPase, and 5 -(NAl-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger. Physiol Res., 48, 135, 1999. 

In summary, the body of evidence currently available for F. salina indicates that these cells possess two different types of putative photoreceptors, a rhodopsin-like and a hypericin-hke pigment. The hypothesis that a rhodopsin pigment is responsible for phototaxis is supported by several pieces of evidence based on the similarity of its action spectrum to that of P. bursaria, by the effect of metabohc inhibitors such as hydroxylamine and zaprinast, by gene analysis, and by the suggested effect of Hght on membrane conductance. 

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