Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin.
Authorsde Witte P, Agostinis P, Van Lint J, Merlevede W, Vandenheede JR
JournalBiochem Pharmacol
PubMed ID8267642
The naphthodianthrone hypericin produces a potent and irreversible inhibition of the epidermal growth factor (EGF) receptor tyrosine kinase activity. The inhibition was time and temperature dependent but did not depend on EGF activation. The IC50 values obtained were 0.37-8.7 microM with membranes incubated for 30 min at 30 degrees or ... More
Induction of differentiation of the human histocytic lymphoma cell line U-937 by hypericin.
AuthorsKim JI, Park JH, Park HJ, Choi SK, Lee KT
JournalArch Pharm Res
PubMed ID9875513
'Hypericin, a photosensitizing plant pigment, was found to be a potent inducer of differentiation of human myeloid leukemia U-937 cells. At a concentration of 0.2 microM, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ability to induce phagocytosis of latex particles, and ... More
In vivo photodynamic activity of hypericin in transitional cell carcinoma bladder tumors.
AuthorsZupkó I, Kamuhabwa AR, D'Hallewin MA, Baert L, De Witte PA
JournalInt J Oncol
PubMed ID11295062
'In a recent clinical study, we showed that hypericin accumulates selectively in urothelial lesions of the bladder following intravesical administration of the compound in patients. This observation infers that hypericin, a potent photosensitizer, could be used as a selective photodynamic therapy (PDT) tool against superficial bladder cancer. In the present ... More
Localization of two distinct type III phosphatidylinositol 4-kinase enzyme mRNAs in the rat.
AuthorsZólyomi A, Zhao X, Downing GJ, Balla T
JournalAm J Physiol Cell Physiol
PubMed ID10794665
'Inositol lipid kinases generate polyphosphoinositides, important regulators of several cellular functions. We have recently cloned two distinct phosphatidylinositol (PI) 4-kinase enzymes, the 210-kDa PI4KIIIalpha and the 110-kDa PI4KIIIbeta, from bovine tissues. In the present study, the distribution of mRNAs encoding these two enzymes was analyzed by in situ hybridization histochemistry ... More
Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wild-type p53.
AuthorsWeller M, Trepel M, Grimmel C, Schabet M, Bremen D, Krajewski S, Reed JC
JournalNeurol Res
PubMed ID9329022
'Hypericin and tamoxifen are experimental agents for the adjuvant chemotherapy of malignant glioma. We report that hypericin and tamoxifen induce apoptosis of 7 human malignant glioma cell lines in a concentration- and time-dependent manner. Illumination is essential for the cytotoxicity of hypericin but not tamoxifen. Apoptosis is unaffected by inhibitors ... More
Tobacco smoke tumor promoters, catechol and hydroquinone, induce oxidative regulation of protein kinase C and influence invasion and metastasis of lung carcinoma cells.
AuthorsGopalakrishna R, Chen ZH, Gundimeda U
JournalProc Natl Acad Sci U S A
PubMed ID7991611
'Cigarette smoke polyphenolic agents (catechol and hydroquinone) that generate oxidants have been shown to be tumor promoters. Furthermore, oxidants can influence protein kinase C (PKC)-mediated signal transduction. Since terpenoid tumor promoters, phorbol esters, increase invasion and metastasis by activating PKC, we have determined whether polyphenolic agents present in the cigarette ... More
Efficacy of antitumoral photodynamic therapy with hypericin: relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model.
AuthorsChen B, Xu Y, Roskams T, Delaey E, Agostinis P, Vandenheede JR, de Witte P
JournalInt J Cancer
PubMed ID11410877
'We investigated the hypericin-mediated PDT effects on the tumor and normal skin and in correlation with its biodistribution. These studies were carried out on C3H mice bearing RIF-1 tumors. The hypericin distribution and PDT effects were recorded at different intervals (0.5-24 hr) after intravenous injection of a 5-mg/kg dose of ... More
Hypericin photosensitization in aqueous model systems.
AuthorsSenthil V, Jones LR, Senthil K, Grossweiner LI
JournalPhotochem Photobiol
PubMed ID8127939
'Photosensitization of lysozyme, liposomes, ghosts and intact red blood cells (RBC) was investigated for aqueous hypericin. The effects of azide ion, 1,4-diazabicyclo(2.2.2)octane, and superoxide dismutase on photosensitized inactivation of lysozyme in 0.5% Triton X-100 indicate that singlet oxygen is the major inactivating intermediate with a contribution from superoxide. The singlet ... More
Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression.
AuthorsObach RS
JournalJ Pharmacol Exp Ther
PubMed ID10871299
'Commercially available St. John''s wort (Hypericum perforatum) extracts, preparations that are used in the treatment of depression, were examined for the potential to inhibit human cytochrome P450 (CYP) enzyme activities, specifically CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Crude extracts demonstrated inhibition of each of these five enzymes, with CYP2D6, CYP2C9, ... More
Development of a simple, rapid and reproducible HPLC assay for the simultaneous determination of hypericins and stabilized hyperforin in commercial St. John's wort preparations.
Authorsde los Reyes GC, Koda RT
JournalJ Pharm Biomed Anal
PubMed ID11600308
'A reversed-phase HPLC method was developed and validated for the simultaneous determination of hypericins and stabilized hyperforin in St. John''s wort extract. The sample solution was prepared by extraction of the finely powdered extract with methanol-water (80:20, v/v) containing 5% HP-beta-cyclodextrin, and adjusted to pH 2.5 with orthophosphoric acid. Diluted ... More
Photodynamic activity of hypericin in human urinary bladder carcinoma cells.
AuthorsKamuhabwa AR, Agostinis P, D'Hallewin MA, Kasran A, de Witte PA
JournalAnticancer Res
PubMed ID10953329
'Recently, we reported the selective accumulation of hypericin in transitional cell carcinoma cells following intravesical instillation of hypericin in humans. This observation infers that hypericin, a potent photosensitizer, could be used as a selective PDT (photodynamic therapy) tool against superficial bladder cancer. The aim of the present study was to ... More
Novel therapeutic and diagnostic applications of hypocrellins and hypericins.
AuthorsDiwu Z
JournalPhotochem Photobiol
PubMed ID7568399
'Hypocrellins and hypericins, structurally related plant pigments isolated from Hypocrella bambuase and Hypericum respectively, are known photodynamic agents. This review summarizes certain significant advances in the photophysics, photochemistry and photobiology of these pigments in the last 2 years and discusses their prospects as novel therapeutic and diagnostic agents in the ... More
Biochemical activities of extracts from Hypericum perforatum L. 5th communication: dopamine-beta-hydroxylase-product quantification by HPLC and inhibition by hypericins and flavonoids.
AuthorsDenke A, Schempp H, Weiser D, Elstner EF
JournalArzneimittelforschung
PubMed ID10858868
'Extracts from the herb "St. John''s wort" (Hypericum perforatum L.) exhibit beneficial effects on patients suffering from mental depressions. Lack of catecholamine neurotransmitters may be one biochemical mechanism for this problem under discussion. It has been recently reported that alcoholic extracts from Hypericum perforatum inhibit dopamine-beta-hydroxylase (D-beta-H) with an I50 ... More
Time-course of hypericin phototoxicity and effect on mitochondrial energies in EMT6 mouse mammary carcinoma cells.
AuthorsJohnson SA, Dalton AE, Pardini RS
JournalFree Radic Biol Med
PubMed ID9667489
'Photoactivated hypericin produces singlet oxygen and superoxide anion radical; however, the intracellular events contributing to toxicity are unknown. Clonogenic assays of oxygen-dependent hypericin phototoxicity to EMT6 cells have previously shown that 0.5 microM hypericin + 1.5 J cm(-2) fluorescent light is non-toxic and that 1.0 microM hypericin + 1.5 J ... More
Inhibition of duck hepatitis B virus replication by hypericin.
'Hypericin was found to be active against a member of the hepatitis B virus family, duck hepatitis B virus (DHBV). After a single 1 h incubation with hypericin, cells stably-transfected with a clone of DHBV stopped producing infectious virus for several days, though virus-like particles continued to be released into ... More
Sequence specific interaction of the antiretrovirally active drug hypericin with 5'ATGGCAGGATAT3' oligonucleotide: a resonance Raman spectroscopy study.
AuthorsKocisova E, Chinsky L, Miskovsky P
JournalJ Biomol Struct Dyn
PubMed ID9669559
'The resonance Raman spectra of two oligonucleotides and their complexes with potent antiretrovirally and antineoplastic active photochemical drug hypericin are reported. The Raman spectra of two oligonucleotides containing twelve base pairs on addition of hypericin (one and two molecules per one oligonucleotide) were compared. The first one contains the first ... More
Oral bioavailability of active principles from herbal products in humans. A study on Hypericum perforatum extracts using the soft gelatin capsule technology.
AuthorsAgrosi M, Mischiatti S, Harrasser PC, Savio D
JournalPhytomedicine
PubMed ID11194173
'The oral absorption of two known active principles of Hypericum perforatum, namely hyperforin and hypericin, was studied in an open, single dose, two-way, randomized, cross-over study involving 12 healthy subjects (six males and six females). Alcoholic Hypericum extract (300 mg, containing 5% hyperforin and 0.3 % hypericin) was administered in ... More
Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates.
AuthorsFox E, Murphy RF, McCully CL, Adamson PC
JournalCancer Chemother Pharmacol
PubMed ID11221960
'Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment derived from the plant Hypericum perforatum (St John''s Wort). The compound has been synthesized and shown to inhibit the growth of malignant glioma cell lines in vitro via inhibition of protein kinase C. Oral hypericin has entered clinical trials in adults ... More
Acute effects of LI 160 (extract of Hypericum perforatum, St John's wort) and two of its constituents on neuroendocrine responses in the rat.
AuthorsFranklin M, Chi JD, Mannel M, Cowen PJ
JournalJ Psychopharmacol
PubMed ID11198053
'Extracts of Hypericum perforatum (St John''s wort), such as LI 160, which are effective antidepressants have several active constituents. Their mode of action in depression, however, is unclear. In the present investigation, we assessed the effect of equivalent doses of LI 160 and two of its components, hypericin and hyperforin ... More
Antiretroviral activity of synthetic hypericin and related analogs.
AuthorsKraus GA, Pratt D, Tossberg J, Carpenter S
JournalBiochem Biophys Res Commun
PubMed ID1699534
'Hypericin and pseudohypericin are naturally occurring polycyclic quinones which have recently been shown to inhibit the infectivity of several retroviruses, including human immunodeficiency virus. To better understand the antiviral mechanisms of these compounds, hypericin and a series of analogous quinones were synthesized and tested for anti-retroviral activity against equine infectious ... More
New potential photodynamic therapeutic anti-cancer agents: synthesis and characterization of demethoxy amino-substituted hypocrellins.
AuthorsWu T, Xu S, Shen J, Song A, Chen S, Zhang M, Shen T
JournalAnticancer Drug Des
PubMed ID11200504
'A novel method was used to obtain demethoxy amino-substituted hypocrellin derivatives. The reaction condition was mild and amino substitution occurred at position 2 or 11 of hypocrellins with high yield. The photophysical and photochemical properties of the amino-substituted hypocrellins derivatives were investigated, and their significantly enhanced red absorptivities and strong ... More
Photosensitization is required for inactivation of equine infectious anemia virus by hypericin.
AuthorsCarpenter S, Kraus GA
JournalPhotochem Photobiol
PubMed ID1707176
'Hypericin, a photoreactive polycyclic quinone, was found to dramatically reduce infectivity of cell-free stocks of equine infectious anemia virus. However, the antiviral activity of hypericin was completely dependent on the presence of light. Short periods of photosensitization resulted in a partial loss of reverse transcriptase activity and complete inhibition of ... More
Hypericum perforatum (St John's Wort): a non-selective reuptake inhibitor? A review of the recent advances in its pharmacology.
AuthorsNathan PJ
JournalJ Psychopharmacol
PubMed ID11277608
'Hypericum possesses a unique pharmacology in that it displays the pharmacology of many classes of antidepressants and new mechanisms not typical of standard antidepressants. The most potent of all its action is the moderate to high potency for inhibition of the reuptake of monoamines, serotonin, dopamine and noradrenaline and the ... More
Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.
AuthorsKerb R, Brockmöller J, Staffeldt B, Ploch M, Roots I
JournalAntimicrob Agents Chemother
PubMed ID8878586
'Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St. John''s Wort extract LI 160, a plantal antidepressant. Oral administration of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH resulted in ... More
Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity.
AuthorsTakahashi I, Nakanishi S, Kobayashi E, Nakano H, Suzuki K, Tamaoki T
JournalBiochem Biophys Res Commun
PubMed ID2558652
'Hypericin and pseudohypericin which have been isolated from plants of the Hypericum family are aromatic polycyclic diones. Daniel Meruelo et. al. have reported that hypericin and pseudohypericin showed potent antiretroviral activity including anti-human immunodeficiency virus (1,2). However, the mechanism of these antiretroviral activities has not been clarified. In the course ... More
Photosensitized inhibition of growth factor-regulated protein kinases by hypericin.
AuthorsAgostinis P, Vandenbogaerde A, Donella-Deana A, Pinna LA, Lee KT, Goris J, Merlevede W, Vandenheede JR, De Witte P
JournalBiochem Pharmacol
PubMed ID7786302
'The naphthodianthrone hypericin causes a photosensitized inhibition of protein kinases involved in growth factor signalling pathways. Nanomolar concentrations of hypericin inhibit the protein tyrosine kinase activities (PTK) of the epidermal growth factor receptor and the insulin receptor, while being ineffective towards the cytosolic protein tyrosine kinases Lyn, Fgr, TPK-IIB and ... More
Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin.
AuthorsAlecu M, Ursaciuc C, Hãlãlãu F, Coman G, Merlevede W, Waelkens E, de Witte P
JournalAnticancer Res
PubMed ID9891535
'Hypericin displays antiproliferative and cytotoxic effects on tumor cells. This effect depends on photodynamic activation with visible light and oxygen. Hence, we explored its potential use in treating skin cancer. Eight patients with squamous cell carcinoma (SCC) and eleven patients with basal cell carcinoma (BCC) were treated topically with hypericin. ... More
Incidence and clinical relevance of the interactions and side effects of Hypericum preparations.
AuthorsSchulz V
JournalPhytomedicine
PubMed ID11315759
'Observational studies with preparations of St. John''s wort have recorded an incidence of adverse events (AE) among those treated of between 1 and 3%. This is some ten times less than with synthetic antidepressants. The most common adverse events (1 per 300000 treated cases) among the spontaneous reports in the ... More
Cytotoxicity and antiproliferative effect of hypericin and derivatives after photosensitization.
AuthorsVandenbogaerde AL, Delaey EM, Vantieghem AM, Himpens BE, Merlevede WJ, de Witte PA
JournalPhotochem Photobiol
PubMed ID9477769
'The toxicity on three human tumor cell lines (A431, HeLa and MCF7) of five phenanthroperylenequinones (hypericin and derivatives) and two perylenequinones (cercosporin and calphostin C) was investigated after photosensitization (4 J/cm2). Furthermore, the antiproliferative effect on HeLa cells was studied for the phenanthroperylenequinones. Hypericin, 2,5-dibromohypericin, 2,5,9,12-tetrabromohypericin and perylenequinones displayed a ... More
Hypericin: a potential antiglioma therapy.
AuthorsCouldwell WT, Gopalakrishna R, Hinton DR, He S, Weiss MH, Law RE, Apuzzo ML, Law RE
JournalNeurosurgery
PubMed ID7808614
'Hypericin, a polycyclic aromatic dione isolated from plants, is presently being clinically evaluated as an antiviral agent in the treatment of human immunodeficiency virus (HIV) infection. In addition, it is known to be a potent protein kinase C inhibitor. To evaluate its potential as an inhibitor of glioma growth, an ... More
Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection.
AuthorsJacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee D, Spritzler J, Prince AM
JournalAntimicrob Agents Chemother
PubMed ID11158749
'Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral ... More
Growth inhibition and apoptosis in human neuroblastoma SK-N-SH cells induced by hypericin, a potent inhibitor of protein kinase C.
AuthorsZhang W, Lawa RE, Hintona DR, Su Y, Couldwell WT
JournalCancer Lett
PubMed ID7553605
'The effect of hypericin, an antiviral agent and inhibitor of protein kinase C (PKC), on cell proliferation and programmed death was investigated in the human neuroblastoma cell line SK-N-SH. Hypericin induced significant growth inhibition in a dose-dependent manner demonstrated by a microculture tetrazolium (MTT) assay. DNA isolated from cells treated ... More
St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties.
AuthorsBarnes J, Anderson LA, Phillipson JD
JournalJ Pharm Pharmacol
PubMed ID11370698
'The chemical composition of St. John's wort has been well-studied. Documented pharmacological activities, including antidepressant, antiviral, and antibacterial effects, provide supporting evidence for several of the traditional uses stated for St John's wort. Many pharmacological activities appear to be attributable to hypericin and to the flavonoid constituents; hypericin is also ... More
Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8.
AuthorsSchempp CM, Simon-Haarhaus B, Termeer CC, Simon JC
JournalFEBS Lett
PubMed ID11277999
'Hypericin (HYP) is a photosensitizing pigment from Hypericum perforatum that displays cytotoxic effects in neoplastic cell lines. Therefore, HYP is presently under consideration as a new anticancer drug in photodynamic therapy. Here, we investigated the mechanism of action of HYP photo-induced apoptosis of Jurkat cells compared to the cytostatic drug ... More
Single-dose and steady-state administration of Hypericum perforatum extract (St John's Wort) does not influence skin sensitivity to UV radiation, visible light, and solar-simulated radiation.
AuthorsSchempp CM, Müller K, Winghofer B, Schulte-Mönting J, Simon JC
JournalArch Dermatol
PubMed ID11295948
Hypericin and its photodynamic action.
AuthorsDurán N, Song PS
JournalPhotochem Photobiol
PubMed ID3529141
The chemical and biological properties of hypericin--a compound with a broad spectrum of biological activities.
AuthorsLavie G, Mazur Y, Lavie D, Meruelo D
JournalMed Res Rev
PubMed ID7739292
Research at the Interface between Chemistry and Virology: Development of a Molecular Flashlight.
AuthorsKraus GA, Zhang W, Fehr MJ, Petrich JW, Wannemuehler Y, Carpenter S
JournalChem Rev
PubMed ID11848763
Antiviral activity of the photoactive plant pigment hypericin.
AuthorsLopez-Bazzocchi I, Hudson JB, Towers GH
JournalPhotochem Photobiol
PubMed ID1658826
The polycyclic compound hypericin, a known photodynamic agent, was investigated for antiviral activity in the presence and absence of light. The three viruses tested: murine cytomegalovirus; Sindbis virus; and human immunodeficiency virus type 1, were all susceptible to hypericin; but these antiviral activities were considerably enhanced, in a dose-dependent manner, ... More
Is the excited-state H-atom transfer in hypericin concerted?
AuthorsPark J, Datta A, Chowdhury PK, Petrich JW
JournalPhotochem Photobiol
PubMed ID11272722
The excited-state intramolecular H-atom transfer of hypericin (Hyp) was investigated as a function of pH in monodispersed reverse micelles formed by sodium bis(2-ethylhexyl)sulfosuccinate/heptane/water and in complexes with Tb3+ under conditions in which one of the two carbonyl groups of Hyp is incapable of accepting a hydrogen atom. The results of ... More
Hypocrellin, from Hypocrella bambuase, is phototoxic to human immunodeficiency virus.
Hypocrellin, a photodynamic perylene quinonoid isolated from the Chinese medicinal fungus Hypocrella bambuase, was evaluated for antiviral activity against the human immunodeficiency virus (HIV-1). Hypocrellin was phototoxic to HIV-1, almost as good as the structurally similar plant pigment hypericin, and like hypericin its activity required visible light. In contrast peroxyhypocrellin ... More
Seasonal variation in hypericin content of Hypericum perforatum L. (St. John's Wort).
AuthorsSouthwell IA, Bourke CA
JournalPhytochemistry
PubMed ID11261576
Hypericin and pseudohypericin, bioactive constituents in St. John's Wort (Hypericum perforatum), have been determined in the soft tops of the plant that are most likely to be browsed by foraging livestock. In two consecutive seasons, the hypericin/pseudohypericin concentration in a broad leaf biotype varied from a winter minimum of less ... More
Absorbance data of hypericin and pseudohypericin used as reference compounds for medicinal plant analysis.
AuthorsWirz A, Meier B, Sticher O
JournalPharmazie
PubMed ID11210670
The evaluation of the absorbance data of hypericin and pseudohypericin revealed the molar/specific coefficients of absorbance in methanol-pyridine (99:1, v/v) at the maximum of the longest wavelength to be 51936/1030 and 43486/836, respectively. The absorbance data of hypericin were also determined in methanol. They were not significantly different from those ... More
Laser photosensitization of cells by hypericin.
AuthorsAndreoni A, Colasanti A, Colasanti P, Mastrocinque M, Riccio P, Roberti G
JournalPhotochem Photobiol
PubMed ID8041807
Administering a light dose of 90 J/cm2 at 599 nm during incubation with hypericin to a highly differentiated normal epithelial cell line (FRTL-5), derived from Fisher rat thyroid, and to a neoplastic cell line (MPTK-6), derived from the lung metastases of a thyroid carcinoma induced in Fisher rats, produces cell ... More
The role of oxygen in the antiviral activity of hypericin and hypocrellin.
AuthorsPark J, English DS, Wannemuehler Y, Carpenter S, Petrich JW
JournalPhotochem Photobiol
PubMed ID9796444
The light-induced antiviral activity of hypericin and hypocrellin in the presence and absence of oxygen was examined under experimental conditions where the effect of oxygen depletion could be quantified. There was a significant reduction of light-induced antiviral activity of hypericin and hypocrellin under hypoxic conditions. Interestingly, antiviral activity of hypocrellin ... More
Natural products derived from plants as potential drugs for the photodynamic destruction of tumor cells.
AuthorsEbermann R, Alth G, Kreitner M, Kubin A
JournalJ Photochem Photobiol B
PubMed ID9002245
Chlorophyll and some of its synthetically produced derivatives are important sensitizers in photodynamic cancer therapy. Other natural products from plants with light dependent activity include quinones like hypericin and fagopyrin. These compounds have extended pi-electron systems which upon photoexcitation with visible light are responsible for singlet oxygen production. Other plant ... More
Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus.
A number of anthraquinones, anthrones and anthraquinone derivatives were evaluated for antiviral activity against human cytomegalovirus (HCMV) as well as for cytotoxicity. Of those compounds evaluated, quinalizarin, emodin, rhein, hypericin, protohypericin, alizarin, emodin bianthrone and emodin anthrone showed antiviral activity against a normal laboratory HCMV strain, AD-169. When tested against ... More
Hypericin-induced photosensitization of HeLa cells leads to apoptosis or necrosis. Involvement of cytochrome c and procaspase-3 activation in the mechanism of apoptosis.
AuthorsVantieghem A, Assefa Z, Vandenabeele P, Declercq W, Courtois S, Vandenheede JR, Merlevede W, de Witte P, Agostinis P
JournalFEBS Lett
PubMed ID9862416
Here we report that photoactivated hypericin can induce either apoptosis or necrosis in HeLa cells. Under apoptotic conditions the cleavage of poly(ADP-ribose) polymerase (PARP) into the 85-kDa product is blocked by the caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk) and benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (z-DEVD-fmk). Both inhibitors protect cells from apoptosis but cannot prevent hypericin-induced necrosis. ... More
Photodynamic therapy efficacy and tissue distribution of hypericin in a mouse P388 lymphoma tumor model.
AuthorsChen B, de Witte PA
JournalCancer Lett
PubMed ID10755394
The phototherapeutic properties and tissue distribution of hypericin were investigated in DBA/2 mice bearing subcutaneously transplanted P388 lymphoma cells. The efficacy of the photodynamic therapy (PDT) 2 h after administration of hypericin (2, 5, or 20 mg/kg, i.p., 120 J/cm2, 595 nm) was substantially greater than the efficacy after a ... More
Photosensitization of aqueous model systems by hypericin.
AuthorsSenthil V, Longworth JW, Ghiron CA, Grossweiner LI
JournalBiochim Biophys Acta
PubMed ID1739734
Absorption and fluorescence measurements of purified hypericin (HY) were made in various media. Photosensitization of two aqueous systems was investigated: resealed red blood cell membranes (ghosts) and hen lysozyme (Lys). Solubilization of HY by ghost membranes was shown by means of diffuse reflectance spectroscopy. Visible light irradiation of the ghosts ... More
A comparative study on the photocytotoxicity of hypericin on A431 cells using three different assays.
AuthorsUgwu F, Vandenbogaerde AL, Merlevede WJ, de Witte PA
JournalAnticancer Res
PubMed ID9615785
BACKGROUND: Three assay models were adopted for assessing the photocytotoxicity of hypericin on A431 cells. The cells were incubated for 1 hour or 24 hours with hypericin to evaluate the importance of the incubation period on the exerted photocytotoxicity. MATERIALS AND METHODS: A neutral red, an antiproliferative and a tetrazolium-reduction ... More
Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor.
AuthorsZhang W, Law RE, Hinton DR, Couldwell WT
JournalCancer Lett
PubMed ID9570383
The effect of hypericin, an antiviral drug and a potent protein kinase C (PKC) inhibitor, on glioma cell invasion was investigated in vitro. Treatment of the established human glioblastoma cell line, T98G, with 1 microM hypericin for 24 h resulted in a significant inhibition of the cell invasion through an ... More
Photodynamic inactivation of radiation leukemia virus produced from hypericin-treated cells.
AuthorsDegar S, Lavie G, Meruelo D
JournalVirology
PubMed ID7504371
Hypericin is a polycyclic, aromatic, naphthodianthrone which has been shown to possess in vivo and in vitro antiretroviral activity. To gain further insight into the mechanism(s) by which hypericin exerts its antiretroviral effects, we have studied Radiation Leukemia virus (RadLV) produced from cells pulse-treated with hypericin. Hypericin-treatment did not inhibit ... More
Synergistic effect of photodynamic therapy with hypericin in combination with hyperthermia on loss of clonogenicity of RIF-1 cells.
AuthorsChen B, Xu Y, Agostinis P, De Witte PA,
JournalInt J Oncol
PubMed ID11351263
Hypericin is a natural photosensitizer produced in plants of the genus Hypericum. The compound exhibits a potent phototoxicity both in vitro and in vivo. In the present study we investigated the effect of hypericin-mediated PDT on hyperthermia (43 degrees C) in RIF-1 cell line. Our results demonstrated a synergistic effect ... More
Chemiluminescent activation of the antiviral activity of hypericin: a molecular flashlight.
AuthorsCarpenter S, Fehr MJ, Kraus GA, Petrich JW
JournalProc Natl Acad Sci U S A
PubMed ID7991618
Hypericin is a naturally occurring photosensitizer that displays potent antiviral activity in the presence of light. The absence of light in many regions of the body may preclude the use of hypericin and other photosensitizers as therapeutic compounds for the treatment of viral infections in vivo. The chemiluminescent oxidation of ... More
Characterization of the interaction of hypericin with protein kinase C in U-87 MG human glioma cells.
AuthorsKocanova S, Hornakova T, Hritz J, Jancura D, Chorvat D, Mateasik A, Ulicny J, Refregiers M, Maurizot JC, Miskovsky P,
JournalPhotochem Photobiol
PubMed ID16396605
A fluorescence imaging technique was used to monitor intracellular localization of protein kinase C (PKC) in U-87 MG human glioma cells in the presence of hypericin (Hyp) and phorbol 12-myristate-13-acetate (PMA). It is shown that PKC localization, which reflects its activity, is influenced by Hyp and this influence is different ... More
Phosphorylation of Bcl-2 in G2/M phase-arrested cells following photodynamic therapy with hypericin involves a CDK1-mediated signal and delays the onset of apoptosis.
AuthorsVantieghem A, Xu Y, Assefa Z, Piette J, Vandenheede JR, Merlevede W, De Witte PA, Agostinis P,
JournalJ Biol Chem
PubMed ID12101183
The role of Bcl-2 in photodynamic therapy (PDT) is controversial, and some photosensitizers have been shown to induce Bcl-2 degradation with loss of its protective function. Hypericin is a naturally occurring photosensitizer with promising properties for the PDT of cancer. Here we show that, in HeLa cells, photoactivated hypericin does ... More
Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals sigma receptor binding.
AuthorsRaffa RB
JournalLife Sci
PubMed ID9585174
The mechanism of the antidepressant action of St. John's wort (Hypericum perforatum) remains unknown. A central component similar to that of the other clinically-popular antidepressants (e.g., inhibitors of 5-HT or norepinephrine reuptake or MAO) is suspected to play a role, but other mechanisms distinct from the SSRIs, NSRIs or MAOIs ... More
Photochemical effects and hypericin photosensitized processes in collagen.
AuthorsYova D, Hovhannisyan V, Theodossiou T
JournalJ Biomed Opt
PubMed ID11178580
Emission and excitation spectra of collagen were recorded in the ultraviolet and visible regions. The existence of several types of chromophores absorbing and emitting throughout these spectral regions was observed. It was shown that laser irradiation at 355 and 532 nm caused collagen fluorescence photobleaching by 30%, when the delivered ... More
Differential cytotoxic effects induced after photosensitization by hypericin.
AuthorsVandenbogaerde AL, Cuveele JF, Proot P, Himpens BE, Merlevede WJ, de Witte PA
JournalJ Photochem Photobiol B
PubMed ID9203374
The cytotoxic effects of the natural photosensitizing agent hypericin were evaluated. A dramatic difference in the sensitivity of several different human and mouse cell lines towards photoactivated hypericin (4 J cm-2) was demonstrated using a neutral red assay (e.g. A431, IC50 = 0.14 +/- 0.02 microM; HeLa, IC50 = 0.32 ... More
Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro.
AuthorsZhang W, Anker L, Law RE, Hinton DR, Gopalakrishna R, Pu Q, Gundimeda U, Weiss MH, Couldwell WT
JournalClin Cancer Res
PubMed ID9816239
Hypericin, an antidepressant and antiviral agent being evaluated in phase I and II trials for patients with HIV infection, is known to be a potent protein kinase C inhibitor. We have investigated its effects on cellular response to radiation via a tetrazolium-formazan cell growth rate assay using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide ... More
Hypericin-based fluorescence diagnosis of bladder carcinoma.
AuthorsD'Hallewin MA, Kamuhabwa AR, Roskams T, De Witte PA, Baert L
JournalBJU Int
PubMed ID11966641
OBJECTIVE: To determine the use of hypericin instillation for the fluorescent detection of papillary bladder cancer and carcinoma in situ. PATIENTS AND METHODS: Eighty-seven patients with papillary bladder cancer and/or carcinoma in situ received instillations with 40 mL of an 8 micromol/L hypericin solution for at least 2 h. Fluorescent ... More
Photodynamically induced cytotoxicity of hypericin dye on human fibroblast cell line MRC5.
AuthorsHadjur C, Richard MJ, Parat MO, Favier A, Jardon P
JournalJ Photochem Photobiol B
PubMed ID7714674
The possible application of hypericin (hyp) in the photodynamic therapy (PDT) of cancer was investigated using the human fibroblast cell line MRC5. In aerobic conditions, at pH 7.4, irradiation of MRC5 cells was carried out with different doses of visible light and different doses of hyp. A low concentration of ... More
Photocytotoxic effect of pseudohypericin versus hypericin.
AuthorsVandenbogaerde AL, Kamuhabwa A, Delaey E, Himpens BE, Merlevede WJ, de Witte PA
JournalJ Photochem Photobiol B
PubMed ID9868799
Pseudohypericin and hypericin, the major photosensitizing constituents of Hypericum perforatum, are believed to cause hypericism. Since hypericin has been proposed as a photosensitizer for photodynamic cancer therapy, the photocytotoxicity of its congener pseudohypericin has been investigated. The presence of foetal calf serum (FCS) or albumin extensively inhibits the photocytotoxic effect ... More
Laser chemotherapy of human carcinoma cells with three new anticancer drugs.
AuthorsEshraghi AA, Castro DJ, Paiva MB, Graeber IP, Jongewaard N, Arshadnia S, Lamas G, Soudant J, Saxton RE
JournalJ Clin Laser Med Surg
PubMed ID9467337
A new experimental therapy for squamous carcinoma was tested by sensitizing human tumor cells with light-sensitive anticancer drugs followed by laser illumination at visible or infrared wavelengths. The anthrapyrazole DUP-941 and the isoquinoline derivative DUP-840 were compared with the dianthraquinone hypericin. P3 human squamous carcinoma cells were incubated for 2 ... More
Light-dependent inhibition of protein kinase C and superoxide generation of neutrophils by hypericin, an antiretroviral agent.
AuthorsUtsumi T, Okuma M, Utsumi T, Kanno T, Yasuda T, Kobuchi H, Horton AA, Utsumi K
JournalArch Biochem Biophys
PubMed ID7840655
Hypericin, a photosensitizing plant pigment, has antiretroviral activity. When exposed to light, the inhibition of Friend leukemia virus (FLV)-induced splenomegaly by hypericin was increased. The ID50 was decreased to less than 2.5 micrograms/mouse by exposure to tungsten light (29 x 10(-3) W/cm2 for 3 min). This pigment inhibited phorbol 12-myristate ... More
Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation.
AuthorsLenard J, Rabson A, Vanderoef R
JournalProc Natl Acad Sci U S A
PubMed ID7678335
The mechanism of the antiviral activity of hypericin was characterized and compared with that of rose bengal. Both compounds inactivate enveloped (but not unenveloped) viruses upon illumination by visible light. Human immunodeficiency and vesicular stomatitis viruses were photodynamically inactivated by both dyes at nanomolar concentrations. Photodynamic inactivation of fusion (hemolysis) ... More
Hypericin in phototherapy.
AuthorsKoren H, Schenk GM, Jindra RH, Alth G, Ebermann R, Kubin A, Koderhold G, Kreitner M
JournalJ Photochem Photobiol B
PubMed ID9002247
We describe the first local use of hypericin as photosensitizer for photodynamic therapy in a patient with recurrent malignant mesothelioma. Hypericin is a polycyclic quinone, which has been shown to possess in vivo and in vitro antiretroviral and photosensitizing activity; moreover, it is used in depressive disorders. The semiquinone radical, ... More
Kinetics and yield of singlet oxygen photosensitized by hypericin in organic and biological media.
AuthorsEhrenberg B, Anderson JL, Foote CS
JournalPhotochem Photobiol
PubMed ID9723207
The spectroscopy and photophysics of the photosensitizer hypericin when in homogeneous solutions and when bound to liposomes were studied. Hypericin was found to partition efficiently into DMPC liposomes, with a binding constant of 58 (mg lipid/mL)-1. In these liposomes the singlet oxygen production quantum yield was 0.43 +/- 0.09. To ... More
Chlamydia pneumoniae inhibits apoptosis in human peripheral blood mononuclear cells through induction of IL-10.
AuthorsGeng Y, Shane RB, Berencsi K, Gonczol E, Zaki MH, Margolis DJ, Trinchieri G, Rook AH
JournalJ Immunol
PubMed ID10799921
Chlamydia pneumoniae is a common cause of pulmonary infection, with serum positivity in at least 50% of the general population. In this study, we report that human PBMCs exposed to C. pneumoniae are resistant to apoptosis induced by the potent photoactivated chemotherapeutic agents 8-methoxypsoralen and hypericin. In contrast, PBMCs treated ... More
Photooxidation of lens alpha-crystallin by hypericin (active ingredient in St. John's Wort).
AuthorsSchey KL, Patat S, Chignell CF, Datillo M, Wang RH, Roberts JE
JournalPhotochem Photobiol
PubMed ID10946573
Hypericin is the active ingredient in the over the counter antidepressant medication St. John's Wort. Hypericin produces singlet oxygen and other excited state intermediates that indicate it should be a very efficient phototoxic agent in the eye. Furthermore it absorbs in the UV and visible range, which means it can ... More
Photodynamic therapy with hypericin in a mouse P388 tumor model: vascular effects determine the efficacy.
AuthorsChen B, Zupkó I, de Witte PA
JournalInt J Oncol
PubMed ID11251168
Hypericin, a polycyclic quinone obtained from plants of the Hypericum genus, exhibits strong photodynamic antitumor effects. In the present study, PDT efficacy of hypericin under different conditions was compared in a P388 mouse tumor model. Plasma and tumor drug measurements and assessment of vascular damage by fluorescein dye exclusion were ... More
Ca2+ release mechanism of primate drug-induced coronary vasospasm.
AuthorsMiyagawa K, Vidgoff J, Hermsmeyer K
JournalAm J Physiol
PubMed ID9227542
Cellular mechanisms of protection against drug-stimulated coronary vasospasm were studied by multiweek estrogen plus progesterone (P) vs. medroxy-progesterone acetate (MPA) treatments by measuring intracellular Ca2+ and protein kinase C (PKC) signals. Ovariectomized monkeys (OVX) were treated by slow-release implants with either P or MPA for 4 wk added to estradiol-17 ... More
Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin.
AuthorsLavie G, Valentine F, Levin B, Mazur Y, Gallo G, Lavie D, Weiner D, Meruelo D
JournalProc Natl Acad Sci U S A
PubMed ID2548193
Administration of the aromatic polycyclic dione compounds hypericin or pseudohypericin to experimental animals provides protection from disease induced by retroviruses that give rise to acute, as well as slowly progressive, diseases. For example, survival from Friend virus-induced leukemia is significantly prolonged by both compounds, with hypericin showing the greater potency. ... More
Human immunodeficiency virus type 1 cDNA integration: new aromatic hydroxylated inhibitors and studies of the inhibition mechanism.
AuthorsFarnet CM, Wang B, Hansen M, Lipford JR, Zalkow L, Robinson WE, Siegel J, Bushman F
JournalAntimicrob Agents Chemother
PubMed ID9736543
Integration of the human immunodeficiency virus type 1 (HIV-1) cDNA is a required step for viral replication. Integrase, the virus-encoded enzyme important for integration, has not yet been exploited as a target for clinically useful inhibitors. Here we report on the identification of new polyhydroxylated aromatic inhibitors of integrase including ... More
Hypocrellin and hypericin-induced phototoxicity of HL-60 cells: apoptosis or necrosis?
AuthorsMirossay A, Mojzis J, Tóthová J, Hájiková M, Lacková A, Mirossay L
JournalPhytomedicine
PubMed ID11194175
Hypericin and hypocrellin are potential antiviral and antineoplastic agents with multiple modes of light-induced biological activity connected with a production of singlet oxygen and/or excited-state proton transfer and consequent pH drop formation in the drugs environment. In present work light-induced cytotoxicity of hypericin and hypocrellin and mechansim of cell death ... More
Design, synthesis and investigation of mechanisms of action of novel protein kinase C inhibitors: perylenequinonoid pigments.
AuthorsDiwu Z, Zimmermann J, Meyer T, Lown JW
JournalBiochem Pharmacol
PubMed ID7508231
A series of perylenequinonoid pigments (PQPs) and related compounds were synthesized and screened for the inhibition of protein kinase C (PKC), a key enzyme involved in cellular differentiation and proliferation, and a potential target for anticancer and antiviral chemotherapeutic drugs. This study has established PQPs as efficient PKC inhibitors, and ... More
Photocytotoxicity of hypericin in normoxic and hypoxic conditions.
AuthorsDelaey E, Vandenbogaerde A, Merlevede W, de Witte P
JournalJ Photochem Photobiol B
PubMed ID11073312
The normoxic and hypoxic photocytotoxicity of hypericin has been examined on A431 cells as assessed by the Neutral Red method, using cell-culture flasks made of polystyrene and glass, different hypericin concentrations and light fluences. Using polystyrene flasks, lower hypoxic photoactivities of hypericin than those in normoxic conditions are seen under ... More
Antioxidant enzyme response to hypericin in EMT6 mouse mammary carcinoma cells.
AuthorsJohnson SA, Pardini RS
JournalFree Radic Biol Med
PubMed ID9586812
Antioxidant enzyme activities were measured following exposure to hypericin +/- irradiation in EMT6 cells. CuZnSOD and catalase activities peaked within 0.5 h following irradiation for nontoxic 0.5 microM hypericin and toxic 1.0 microM hypericin. Catalase remained elevated up to 3 h for 1.0 microM hypericin + light. MnSOD activity was ... More
Fluorescence detection of flat bladder carcinoma in situ after intravesical instillation of hypericin.
AuthorsD'Hallewin MA, De Witte PA, Waelkens E, Merlevede W, Baert L
JournalJ Urol
PubMed ID10893582
PURPOSE: We determined the sensitivity and specificity of detecting flat bladder carcinoma in situ through fluorescent detection after intravesical hypericin instillations. MATERIALS AND METHODS: The study included 40 patients, of whom 26 presented with macroscopic visible tumor, 9 had a positive cytology without visible tumor and 5 underwent cystoscopy after ... More
Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin.
AuthorsMeruelo D, Lavie G, Lavie D
JournalProc Natl Acad Sci U S A
PubMed ID2839837
Two aromatic polycyclic diones hypericin and pseudohypericin have potent antiretroviral activity; these substances occur in plants of the Hypericum family. Both compounds are highly effective in preventing viral-induced manifestations that follow infections with a variety of retroviruses in vivo and in vitro. Pseudohypericin and hypericin probably interfere with viral infection ... More
Inhibition of bovine immunodeficiency virus by anti-HIV-1 compounds in a cell culture-based assay.
AuthorsTobin GJ, Ennis WH, Clanton DJ, Gonda MA
JournalAntiviral Res
PubMed ID8955850
The bovine immunodeficiency virus (BIV) and human immunodeficiency virus types 1 and 2 (HIV-1 and -2) are members of the lentivirus genus of retroviruses. Although DNA sequences of these viruses have diverged considerably, the BIV genome organization, function of structural and regulatory genes, and replication cycle are very similar to ... More
Photodynamic effects of hypericin on lipid peroxidation and antioxidant status in melanoma cells.
AuthorsHadjur C, Richard MJ, Parat MO, Jardon P, Favier A
JournalPhotochem Photobiol
PubMed ID8760577
Photodynamic-induced cytotoxicity by hypericin (HYP) was studied on three human melanoma cell lines: one pigmented cell line (G361) and two amelanotic cell lines (M18 and M6). No significant variation in the rate of uptake and in the maximum level of HYP incorporation for the different cells was observed. In the ... More
Intratumoral hypericin and KTP laser therapy for transplanted squamous cell carcinoma.
AuthorsChung PS, Rhee CK, Kim KH, Paek W, Chung J, Paiva MB, Eshraghi AA, Castro DJ, Saxton RE
JournalLaryngoscope
PubMed ID10942132
OBJECTIVES/HYPOTHESIS: To test intratumoral photodynamic therapy (IPDT) as a new treatment for squamous cell carcinoma in a preclinical tumor model. STUDY DESIGN AND METHODS: Human P3 squamous carcinoma cells were transplanted subcutaneously in athymic nude mice and allowed to grow into 300- to 500-mm3 tumors. Hypericin dye at 1 microg/gm ... More
Hypericin inhibits choroidal endothelial cell proliferation and cord formation in vitro.
AuthorsKimura H, Harris MS, Sakamoto T, Gopalakrishna R, Gundimeda U, Cui JZ, Spee C, Hinton DR, Ryan SJ
JournalCurr Eye Res
PubMed ID9330847
PURPOSE: To evaluate the effect of hypericin on bovine choroidal endothelial cell proliferation and cord formation and on protein kinase C activity. METHODS: The effect of hypericin (0.1-5 microM) on bovine choroidal endothelial cell proliferation was determined by cell number counting and a 3H-thymidine uptake assay in media containing 1, ... More
Binding, uptake, and transport of hypericin by Caco-2 cell monolayers.
AuthorsSattler S, Schaefer U, Schneider W, Hoelzl J, Lehr CM
JournalJ Pharm Sci
PubMed ID9344168
The biological evaluation of hypericin in various test models is hampered by its very poor water solubility. In the present study cyclodextrin formulations and liposomal preparations were investigated for improved delivery and solubility of hypericin in aqueous buffer systems. Caco-2 cells, grown to tight monolayers on 96-well tissue culture plates ... More
Effect of light on hypericins contents in fresh flowering top parts and in an extract of St. John's Wort (Hypericum perforatum).
AuthorsPoutaraud A, Di Gregorio F, Tin VC, Girardin P
JournalPlanta Med
PubMed ID11345698
St. John's Wort is a medicinal plant increasingly used for its antidepressive activity. Hypericins are considered as one of the compounds contributing to the activity of the extract. These naphthodianthrones exist in various forms in Hyperici herba. Protopseudohypericin and protohypericin (protopigments) are converted into pseudohypericin and hypericin (pigments) under the ... More
Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed, and malignant T lymphocytes: implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders.
AuthorsFox FE, Niu Z, Tobia A, Rook AH
JournalJ Invest Dermatol
PubMed ID9699738
Hypericin is a photodynamic compound activated by either visible (400-700 nm) or UVA (320-400 nm) light, and has been shown to inhibit the growth of a variety of neoplastic cell types. In this study, hypericin was found to inhibit proliferative responses of malignant T cells derived from the blood of ... More
Solvatochromic effects in the electronic absorption and nuclear magnetic resonance spectra of hypericin in organic solvents and in lipid bilayers.
AuthorsWeitman H, Roslaniec M, Frimer AA, Afri M, Freeman D, Mazur Y, Ehrenberg B
JournalPhotochem Photobiol
PubMed ID11272723
The natural product hypericin was tested in recent years as a biological photosensitizer with a potential for viral and cellular photodamage. We thus studied extensively its spectroscopy and membrane partitioning. Absorption, fluorescence excitation and emission spectra of the sodium salt (HyNa) were measured in 36 protic and aprotic, polar and ... More
Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers.
AuthorsBurstein AH, Horton RL, Dunn T, Alfaro RM, Piscitelli SC, Theodore W
JournalClin Pharmacol Ther
PubMed ID11180020
BACKGROUND: St John's Wort is a popular herbal product used by approximately 7% of patients with epilepsy. Previous reports have described reductions in concentrations of CYP3A4 substrates indinavir and cyclosporine (INN, ciclosporin) associated with St John's Wort. OBJECTIVE: Our objective was to determine the effect of St John's Wort on ... More
Agents for treating human immunodeficiency virus infection.
AuthorsAcosta EP, Fletcher CV
JournalAm J Hosp Pharm
PubMed ID7801986
The replicative cycle of the human immunodeficiency virus (HIV) is reviewed, and currently used and investigational agents directed against the virus are discussed. The first step in the replication of HIV is selective binding of the envelope glycoprotein to CD4 receptors located on T lymphocytes. The virion is then uncoated ... More
Light-induced photoactivation of hypericin affects the energy metabolism of human glioma cells by inhibiting hexokinase bound to mitochondria.
AuthorsMiccoli L, Beurdeley-Thomas A, De Pinieux G, Sureau F, Oudard S, Dutrillaux B, Poupon MF
JournalCancer Res
PubMed ID9865736
Glucose-dependent energy required for glioma metabolism depends on hexokinase, which is mainly bound to mitochondria. A decrease in intracellular pH leads to a release of hexokinase-binding, which in turn decreases glucose phosphorylation, ATP content, and cell proliferation. Thus, intracellular pH might be a target for therapy of gliomas, and a ... More
Pharmacodynamic effects of two different hypericum extracts in healthy volunteers measured by quantitative EEG.
AuthorsSchellenberg R, Sauer S, Dimpfel W
JournalPharmacopsychiatry
PubMed ID9684947
A double-blind, randomized, placebo-controlled parallel-group trial (phase I) was performed to evaluate the central pharmacodynamic effects of two hypericum extracts with different contents of hyperforin (0.5% and 5.0%) but identical hypericin content. Three groups of 18 volunteers between 18 and 35 years of age participated in the trial. The volunteers ... More
Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C.
AuthorsJarvis WD, Turner AJ, Povirk LF, Traylor RS, Grant S
JournalCancer Res
PubMed ID7511048
The present studies were undertaken to characterize further the potential role of protein kinase C (PKC) in the regulation of apoptosis in HL-60 promyelocytic leukemia cells. The capacity of acute exposure to specific and nonspecific pharmacological inhibitors of PKC to promote apoptotic DNA fragmentation was examined both quantitatively and qualitatively ... More
Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum.
AuthorsCalapai G, Crupi A, Firenzuoli F, Inferrera G, Squadrito F, Parisi A, De Sarro G, Caputi A
JournalPharmacopsychiatry
PubMed ID11302563
Hypericum perforatum is considered an effective alternative to the synthetic antidepressants in the treatment of mild-to-moderate depression. Recently, we showed that the effects on neurotransmitter contents in different brain regions of laboratory animals are more evident after administration of hypericum extracts containing a higher concentration of flavonoids, thus suggesting that ... More
Hypericin as an inactivator of infectious viruses in blood components.
AuthorsLavie G, Mazur Y, Lavie D, Prince AM, Pascual D, Liebes L, Levin B, Meruelo D
JournalTransfusion
PubMed ID7740610
BACKGROUND: Hypericin is a potent virucidal agent with activity against a broad range of enveloped viruses and retroviruses. The effective virucidal activity emanates from a combination of photodynamic and lipophilic properties. Hypericin binds cell membranes (and, by inference, virus membranes) and crosslinks virus capsid proteins. This action results in a ... More
Inhibition of cellular growth and induction of apoptosis in pituitary adenoma cell lines by the protein kinase C inhibitor hypericin: potential therapeutic application.
AuthorsHamilton HB, Hinton DR, Law RE, Gopalakrishna R, Su YZ, Chen ZH, Weiss MH, Couldwell WT
JournalJ Neurosurg
PubMed ID8755764
Protein kinase C (PKC) is an enzyme involved in the regulation of cellular growth, proliferation, and differentiation in a number of tissues including the anterior pituitary, in which it is also believed to play a role in hormone secretion. Protein kinase C activity and expression have been found to be ... More
Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF-1 mouse tumor model.
AuthorsChen B, Roskams T, Xu Y, Agostinis P, de Witte PA
JournalInt J Cancer
PubMed ID11857421
Hypericin, a polycyclic quinone obtained from plants of the genus Hypericum, has been proven to be a potent photosensitizer. The mechanism of tumor eradication and mode of cell death induced by in vivo photodynamic therapy (PDT) with hypericin were investigated in the present study using 2 therapeutic protocols. RIF-1 tumors ... More
Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent.
AuthorsNishiuchi T, Utsumi T, Kanno T, Takehara Y, Kobuchi H, Yoshioka T, Horton AA, Yasuda T, Utsumi K
JournalArch Biochem Biophys
PubMed ID7487096
We previously reported that phorbol 12-myristate 13-acetate (PMA)-induced superoxide (O2.-) generation of neutrophils was inhibited by hypericin, a photosensitizing pigment found in St. Johnswort (herb Hypericin triquetrifolium Turra), via a mechanism involving protein kinase C (PKC). To obtain further insights into the mechanism of inhibition, the effects of hypericin on ... More
An open-label trial of St. John's Wort (Hypericum perforatum) in obsessive-compulsive disorder.
AuthorsTaylor LH, Kobak KA
JournalJ Clin Psychiatry
PubMed ID10982200
BACKGROUND: Recent interest in and evidence for the efficacy of St. John's wort (Hypericum perforatum) for the treatment of mild-to-moderate depression has led to speculation about its efficacy in other disorders. Hypericum's mechanism of action is postulated to be via inhibition of the synaptosomal uptake of serotonin. As such, there ... More