The Antiviral Agent Hypericin has<i>in vitro</i>Activity against HSV-1 Through Non-Specific Association with Viral and Cellular Membranes

Weber, Norbert D.; Murray, Byron K.; North, James A.; Wood, Steve

doi:10.1177/095632029400500204

Cited by 51 publications

(45 citation statements)

References 23 publications

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“…Taken together, these data obtained for Caco-2 cells under serum free conditions suggest that HY is actively taken up after non-specific binding to membrane lipids (38). In addition, alteration of individual steps of endocytosis and membrane cycling changed the intracellular HY location (39), which also indicate the involvement of energy-dependent processes in uptake and distribution of HY in living cells.…”

Section: Discussionmentioning

confidence: 52%

Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines

Ritz¹,

Wein²,

Dietz³

et al. 2007

Int J Oncol

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Abstract. The poor prognosis of patients suffering from malignant glioma requires further efforts. Photodynamic therapy (PDT) might be a therapeutic option to increase surgical radicality. Hypericin (HY) exhibit high phototoxicity to malignant cells and accumulates to a higher extent in glioblastoma cells as compared to neurons. Therefore, the impact of various experimental parameters on cytotoxicity, intracellular accumulation and phototoxicity of HY was quantitatively assessed in the three human glioblastoma cell lines U373 MG, LN229 and T98G. Additionally, intracellular location of HY was studied with fluorescence microscopic techniques. For all three cell lines, no cytotoxicity was found for incubation concentrations up to 5 μM. For short-time incubation (2 h), maximum HY fluorescence was achieved at an incubation concentration of about 5 μM. However, uptake kinetics of HY was dependent on its incubation concentration. Moreover, increase in HY fluorescence was negligible at 4˚C, which strongly indicates that the compound is taken up by an energy-dependent process. HY exhibited high phototoxicity (at 595 nm) in all three cell lines with ID 50 -values ranging from 0.15 J/cm 2 to 0.22 J/cm 2 , but sensitivity decreased in the order U373 MG > LN229 > T98G. However, assessment of phototoxicity at different wavelengths revealed that highest cell inactivation was achieved at 600 nm. Fluorescence microscopy showed that HY fluorescence arose predominantly from the perinuclear region and the nuclear membrane. Fluorescence pattern of HY was significantly different from those observed for organelle markers staining lysosomes or mitochondria. Location of HY in the plasma membrane was proven by total internal reflection fluorescence microscopy. Thus, the present study demonstrates that glioblastoma cells can be effectively inactivated by HY-PDT after short-time incubation and exposure to low light doses. These results obtained in cell culture are encouraging and justify further evaluation HY-PDT for the treatment of malignant glioma in animal experiments.

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Section: Discussionmentioning

confidence: 52%

Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines

Ritz¹,

Wein²,

Dietz³

et al. 2007

Int J Oncol

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“…Hypericin staining of the plasma membrane has also been described [13,17,18]. It was demonstrated that during a short exposure, hypericin was first concentrated in the cell membrane and then penetrated into the cytoplasm [13,17]. However, other reports [14][15][16] did not show specific staining of the plasma membrane.…”

Section: Introductionmentioning

confidence: 88%

“…In spite of a number of investigations of hypericin [12][13][14][15][16][17][18][19], some aspects related to its intracellular distribution remains unclear and contradictory. Thomas and Pardini [12] described red hypericin fluorescence throughout the cytoplasm and plasma membrane in mammary carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

“…Thomas and Pardini [12] described red hypericin fluorescence throughout the cytoplasm and plasma membrane in mammary carcinoma cells. Hypericin staining of the plasma membrane has also been described [13,17,18]. It was demonstrated that during a short exposure, hypericin was first concentrated in the cell membrane and then penetrated into the cytoplasm [13,17].…”

Section: Introductionmentioning

confidence: 99%

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Intracellular Localisation of Hypericin in Human Glioblastoma and Carcinoma Cell Lines

Uzdensky

Iani

et al. 2001

Lasers Med Sci

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Hypericin, a natural polycyclic quinone extracted from Hypericum perforatum, has been recently shown to be a powerful sensitiser for photodynamic therapy (PDT). However, its intracellular localisation remains unclear and contradictory. In the present work we compared the intracellular localisation of hypericin in three cultured cell lines (adenocarcinoma cells WiDr, carcinoma cells NHIK 3025 and glioblastoma cells D54Mg) with the distribution of fluorescent probes specific to lysosomes (LysoTracker Blue DND-22), mitochondria (MitoTracker Green FM) and endoplasmic reticulum (ERTracker Blue-White DPX). It was shown that the hypericin staining pattern was different compared to the intracellular distribution of mitochondria or lysosomes. Hypericin was concentrated in the perinucleolar cytoplasmic area mainly on one side of the nucleus--the region rich in endoplasmic reticulum and Golgi. Sometimes nuclear envelope was also stained. Plasma membrane was not stained but the dye was often accumulated in the intercellular space between the tightly contacting WiDr cells in colonies. Hypericin concentrations of 10 microM or less were not toxic for WiDr cells in the dark. Orange light (lambda max approximately 600 nm; 6 mW/cm2) killed the cells stained with 1 microM hypericin with LD50 approximately 1 J/cm2.

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“…Hypericin and pseudohypericin have been reported to inhibit several encapsulated viruses in-vitro, including herpes simplex virus types 1 and 2 (Wood et al 1990 ;Weber et al 1994), and human immunodeficiency virus (HIV)-1 (Meruelo et al 1988 ;Lavie et al 1989 ;Hudson et al 1991 ;LopezBazzocchi et al 1991). Hypericin has also been reported to inactivate murine cytomegalovirus (MCMV) and Sindbis virus .…”

Section: Antiviral Activitymentioning

confidence: 99%

St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties

Barnes

Anderson

Phillipson

2001

Journal of Pharmacy and Pharmacology

694

462

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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 reported to be responsible for the photosensitive reactions that have been documented for St. John's wort. With regard to the antidepressant effects of St John's wort, hyperforin, rather than hypericin as originally thought, has emerged as one of the major constituents responsible for antidepressant activity. Further research is required to determine which other constituents contribute to the antidepressant effect.Evidence from randomised controlled trials has confirmed the efficacy of St John's wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomised controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression. There is still a need for further trials to assess the efficacy of St John's wort extracts, compared with that of standard antidepressants, particularly newer antidepressant agents, such as the selective serotonin reuptake inhibitors (recent comparative studies with fluoxetine and sertraline have been conducted). Also, there is a need for further studies in well-defined groups of patients, in different types of depression, and conducted over longer periods in order to determine longterm safety. St John's wort does appear to have a more favourable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication.Concerns have been raised over interactions between St John's wort and certain prescribed medicines (including warfarin, ciclosporin, theophylline, digoxin, HIV protease inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, triptans, oral contraceptives) ; advice is that patients taking these medicines should stop taking St John's wort, generally after seeking professional advice as dose adjustment of conventional treatment may be necessary.

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The Antiviral Agent Hypericin hasin vitroActivity against HSV-1 Through Non-Specific Association with Viral and Cellular Membranes

Cited by 51 publications

References 23 publications

Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines

Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines

Intracellular Localisation of Hypericin in Human Glioblastoma and Carcinoma Cell Lines

St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties

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