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PubMed2004

[Improvement of diversity, trade and conservation of medicinal and aromatic plants].

The significance of medicinal and aromatic plant selection has risen in recent years due to increasing requirements on quality, safety, and efficiency of herbal products. Only selected varieties could guaranty the homogeneity of raw material. The chemical diversity of spontaneous populations is one of the main directions of investigations on medicinal and aromatic plants at the Institute of Botany. The target species under research are following: Origanum vulgare, Thymus spp., Hypericum spp., Achillea millefolium, and Helichrysum arenarium. The analysis of trade figures pointed out that the imported raw material mainly supplies the demands of pharmaceutical industry in Lithuania. The cultivated production covers only 4-6% of the demand for raw material. Wild plant material represents about 29% of total volume used in pharmaceutics. The trade in wild plant species and their resources is regulated by the legislations. In situ and ex situ conservation methods are used to avoid potential danger and existing threats to genetic diversity of medicinal plant species.

Achillea↗
PubMed2004

Selected integrative medicine treatments for depression: considerations for women.

This review evaluates the research published between 1966 and 2004 on several integrative treatments for depression, including omega-3 fatty acids, Hypericum perforatum (St. John's Wort), S-adenosyl-methionine, folate, 5-Hydroxytryptophan, acupuncture, exercise, and light therapy, with a particular emphasis on issues pertinent to women. Data from double-blind, placebo-controlled trials support each of these as treatment interventions for depression. We discuss both the strength of the evidence for each treatment and methodological issues related to interpretation of efficacy. Available data pertaining to considerations in women, including use during pregnancy and breastfeeding and interactions with hormonal therapies are discussed. The reviewed treatments deserve further research. Their appropriate place in the armamentarium of depression treatments for women must be defined. An evidence-based integrative medicine approach brings together treatment options with proven efficacy and the public's desire for complementary and alternative medicine treatments.

5-Hydroxytryptophan↗
PubMed2005

Epidemiology, etiology, and natural treatment of seasonal affective disorder.

There is much more seasonal difference in higher latitudes than in lower latitudes. In a significant portion of the population of the northern United States, the shorter days of fall and winter precipitate a syndrome that can consist of depression, fatigue, hypersomnolence, hyperphagia, carbohydrate craving, weight gain, and loss of libido. If these symptoms persist in the winter, abate as the days grow longer, and disappear in the summer, the diagnosis of seasonal affective disorder (SAD) can be made. Many hypotheses exist regarding the biochemical mechanisms behind the predisposition toward this disease, including circadian phase shifting, abnormal pineal melatonin secretion, and abnormal serotonin synthesis. Although the mechanism(s) behind this disease is not fully known, one treatment appears to address each of the theories. Light therapy is a natural, non-invasive, effective, well-researched method of treatment for SAD. Various light temperatures and times of administration of light therapy have been studied, and a combination of morning and evening exposure appears to offer the best efficacy. Other natural methods of treatment have been studied, including L-tryptophan, Hypericum perforatum (St. John's wort), and melatonin.

Humans↗
PubMed1998

Complementary therapies for depression: an overview.

Depression is one of the most common reasons for using complementary and alternative therapies. The aim of this article is to provide an overview of the evidence available on the treatment of depression with complementary therapies. Systematic literature searches were performed using several databases, reference list searching, and inquiry to colleagues. Data extraction followed a predefined protocol. The amount of rigorous scientific data to support the efficacy of complementary therapies in the treatment of depression is extremely limited. The areas with the most evidence for beneficial effects are exercise, herbal therapy (Hypericum perforatum), and, to a lesser extent, acupuncture and relaxation therapies. There is a need for further research involving randomized controlled trials into the efficacy of complementary and alternative therapies in the treatment of depression.

Acupuncture Therapy↗
PubMed1999

Antimicrobial activity of extracts from the cell cultures of some Turkish medicinal plants.

Twenty-four callus, and eleven cell suspension, cultures were established from Turkish medicinal plants, and crude extracts prepared from them tested against microorganisms to assess their antimicrobial activities in vitro. Of the extracts tested, those belonging to the cell cultures of five of the plant species showed antibacterial activity against mainly three bacteria and a yeast. No activity was observed against herpes simplex viruses, HSV-I and II, but an extract from Hypericum capitatum showed a slight anti-retroviral activity against HIV-I.

Animals↗
PubMed2005

Aristoforin, a novel stable derivative of hyperforin, is a potent anticancer agent.

Hyperforin, a natural product of St. John's wort (Hypericum perforatum L.), has a number of pharmacological activities, including antidepressive and antibacterial properties. Furthermore, hyperforin has pronounced antitumor properties against different tumor cell lines, both in vitro and in vivo. Despite being a promising novel anticancer agent, the poor solubility and stability of hyperforin in aqueous solution limits its potential clinical application. In this study, we present the synthesis of hyperforin derivatives with improved pharmacological activity. The synthesized compounds were tested for their solubility and stability properties. They were also investigated for their antitumor properties, both in vitro and in vivo. One of these hyperforin derivatives, Aristoforin, is more soluble in aqueous solution than hyperforin and is additionally highly stable. Importantly, it retains the antitumor properties of the parental compound without inducing toxicity in experimental animals. These data strongly suggest that Aristoforin has potential as an anticancer drug.

Animals↗
PubMed2005

Hyperolactone C: determination of its absolute configuration by comparison of experimental and calculated CD spectra.

A detailed conformational analysis of hyperolactone C diastereomers and enantiomers ((5R,9R),(5S,9S) and (5S,9R),(5R,9S)) was done with molecular mechanics and density functional theory methods. Time-dependent density functional theory (B3PW91/TZVP) was used to calculate electronic transition energies (UV/vis spectra) and rotational strengths of the respective conformations. The effect of solvation (acetonitrile solution) on excitation energies and electronic circular dichroism was approximated by the polarizable continuum model. By comparison of the simulated CD spectrum with that measured for hyperolactone C isolated from Hypericum lloydii, its absolute configuration can be assigned as (5S,9S).

Acetonitriles↗
PubMed2002

Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF-1 mouse tumor model.

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 were exposed to laser light at either 0.5 hr or 6 hr after hypericin administration (5 mg/kg, i.v.). A significant reduction in tumor perfusion, as determined by the retention of fluorescein in the tumor tissue, was detected immediately after both PDT treatments. Further decrease in tumor perfusion was observed in the hours after treatment. The re-establishment of tumor perfusion, however, occurred 24 hr after 6 hr-interval PDT, but not after 0.5 hr-interval PDT. The kinetics of tumor cell survival estimated by the in vivo/in vitro clonogenic assay revealed no or limited cell death when tumors were explanted immediately after irradiation, whereas a delayed but progressive cell death was detected when tumors remained in situ after both PDT treatments. The detection of nucleosomal DNA fragmentation by agarose gel electrophoresis or TUNEL assay and the assessment of cell morphology by light microscopy indicated that apoptosis was the most prominent tumor response to hypericin-mediated PDT. Furthermore, immunohistochemical analysis of the tumor tissue showed an increased expression of both Fas and Fas ligand after irradiation, suggesting that this cell death pathway might contribute to the overall PDT-induced apoptotic response. In conclusion, our results demonstrate that apoptosis, likely occurring as a result of vascular damage, is responsible for the tumor eradication by PDT with hypericin in this tumor model.

Animals↗
PubMed2004

Fast screening method for the analysis of total flavonoid content in plants and foodstuffs by high-performance liquid chromatography/electrospray ionization time-of-flight mass spectrometry with polarity switching.

A liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) method based on time-of-flight (TOF) MS with polarity switching and continuous exact mass measurement using a LockSpray ion source was developed for fast evaluation of the total flavonoid content in plants and foodstuffs. No complicated sample preparation was needed, but only a dilution of the extracts. A fast generic gradient elution and wide mass range acquisition was used with good sensitivity. The total analysis time was only 23 min. The ion chromatograms for flavonoid compounds were automatically extracted, and the fragmentation patterns obtained using positive ion mode and exact mass data for both polarities were used for the tentative identification of compounds. Software-based automated searching of molecular ions for flavonoids and their glycosides (xylosides/arabinosides, rhamnosides, glucosides/galactosides) from total ion chromatograms was used. The compounds were quantified using quercetin, quercitrin, rutin and kuromanine as external standards and dextromethorphan as an internal standard. The detection limits ranged from 0.01-0.04 microg/mL, while the quantitation ranges obtained were 0.2-10 microg/mL for anthocyanins and 0.2-4 microg/mL for the other flavonoids. The accuracies within these ranges varied between 80-120% and precision was in the range 0-14% (relative standard deviation). Flavonoid contents of two medicinal plants (Hypericum perforatum and Rhodiola rosea), two grape red wines, two orange juices and two green teas were evaluated using the method, and the results obtained were in good agreement with those published previously.

Calibration↗
PubMed2001

Intracellular localisation of hypericin in human glioblastoma and carcinoma cell lines.

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.

Adenocarcinoma↗
PubMed2006

First preclinical evaluation of mono-[123I]iodohypericin as a necrosis-avid tracer agent.

PURPOSE: We have labelled hypericin, a polyphenolic polycyclic quinone found in St. John's wort (Hypericum perforatum), with( 123)I and evaluated mono-[(123)I]iodohypericin (MIH) as a potential necrosis-avid diagnostic tracer agent. METHODS: MIH was prepared by an electrophilic radioiodination method. The new tracer agent was evaluated in animal models of liver infarction in the rat and heart infarction in the rabbit using single-photon emission computed tomography (SPECT), triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional autoradiography and microscopy, and radioactivity counting techniques. RESULTS: Using in vivo SPECT imaging, hepatic and cardiac infarctions were persistently visualised as well-defined hot spots over 48 h. Preferential uptake of the tracer agent in necrotic tissue was confirmed by perfect match of images from post-mortem TTC staining, autoradiography (ARX) and histology. Radioactivity concentration in infarcted tissues was over 10 times (liver; 3.51% ID/g in necrotic tissue vs 0.38% ID/g in normal tissue at 60 h p.i.) and over 6 times (myocardium; 0.36% ID/g in necrotic tissue vs 0.054% ID/g in normal tissue; ratios up to 18 for selected parts on ARX images) higher than in normal tissues. CONCLUSION: The results suggest that hypericin derivatives may serve as powerful necrosis-avid diagnostic agents for assessment of tissue viability.

Animals↗
PubMed2001

Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates.

UNLABELLED: 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 with recurrent malignant glioma. PURPOSE: The present study was performed to characterize the plasma pharmacokinetics (PK) and cerebrospinal fluid (CSF) penetration of hypericin in nonhuman primates. METHODS: Hypericin was administered as an intravenous bolus dose of 2 mg/kg (n = 3) or 5 mg/kg (n = 1). Plasma and CSF (ventricular or lumbar) were sampled prior to administration and at frequent intervals for up to 50 h after administration of the drug. Hypericin concentrations in plasma and CSF were determined using a specific reverse-phase HPLC assay. RESULTS: Mean peak plasma concentration of hypericin following the 2 mg/kg dose was 142 +/- 45 microM. Elimination of hypericin from plasma was biexponential, with an average alpha half-life of 2.8 +/- 0.3 h and average terminal half-life of 26 +/- 14 h. CONCLUSIONS: The 2 mg/kg dose in the nonhuman primate was sufficient to maintain plasma concentrations above 10 microM (the in vitro concentration required for growth inhibition of human glioma cell lines) for up to 12 h. No hypericin was detected in the CSF of any animal (lower limit of detection 0.1 microM); the CSF penetration is therefore less than 1%. A severe dose-limiting photosensitivity skin rash was seen at the 5 mg/kg dose level.

Animals↗
PubMed2004

A metabolomic analysis of medicinal diversity in Huang-qin (Scutellaria baicalensis Georgi) genotypes: discovery of novel compounds.

In vitro manipulation of plant regeneration in the Chinese medicinal species Scutellaria baicalensis Georgi (Huang-qin) resulted in 26 chemically distinct germplasm lines. Antioxidant potential, growth rate and concentration of baicalin, baicalein, melatonin, and wogonin were the selective markers used to identify elite lines. Metabolomic analysis of a subset of the most distinct lines revealed that Huang-qin extracts contained over 2,000 compounds including 781 determined to be of putative medicinal importance as determined by a database search, as well as previously unidentified amino-derivatives of baicalin and wogonin. Huang-qin also contained a metabolite with the same net formula as hyperforin, previously thought to be unique to Hypericum perforatum L. Together these results provide new insights into the biochemical complexity of an important medicinal species and demonstrate the power of in vitro manipulation in combination with untargeted metabolomic screening for the production of new germplasm.

Antioxidants↗
PubMed1989

Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity.

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 of screening specific inhibitors of protein kinase C we have found that both compounds specifically inhibit protein kinase C with IC50 values 1.7 micrograms/ml and 15 micrograms/ml, respectively, and show antiproliferative activity against mammalian cells. These data suggest that antiretroviral activity of hypericin and pseudohypericin could be attributable to the inhibition of some phosphorylation involved by protein kinase C during viral infection of cells.

Animals↗
PubMed1991

Effect of mecoprop drift on some plant species of conservation interest when grown in standardized mixtures in microcosms.

There has been an increasing awareness of potential impacts of herbicide drift on to vegetation in nature reserves and field margin habitats adjacent to treated areas. Previous work using single species bioassays has suggested that the effects of a single drift event are confined close to the sprayer (< 10 m). In the present study eight native dicotyledonous species, with and without a perennial grass (Lolium perenne), were grown in standardized microcosms in order to study (1) the effects of herbicide drift where plants were exposed to competition, and (2) the effects of a second spray application. The microcosms were arranged downwind (0-8 m) of a standard agricultural sprayer applying mecoprop at recommended rates. The effects of the herbicide drift on foliar symptoms of plant damage and end-of-season yield were assessed in each of two years. The main conclusions were that (1) growth of Stachys sylvatica and Lolium perenne (where sown) was enhanced near the sprayer and, (2) six other species (Digitalis purpurea, Galium mollugo, Hypericum hirsutum, Lychnis flos-cuculi, Primula veris and Ranunculus acris) showed some evidence of reduction in either performance (assessed non-destructively after a single exposure) or yield after two exposures. Three species (Lychnis flos-cuculi, Primula veris and Ranunculus acris) showed a reduction in flowering performance. Thus, mecoprop drift affected the aesthetic appearance, possibly the fecundity of some species and the balance between species in these microcosm experiments. The implications of these results for the persistence of attractive plant communities in sensitive areas are discussed.

Journal Article↗
PubMed1986

Plants used in phytotherapy, cosmetics and dyeing in the Pramanda district (Epirus, North-West Greece).

Thirty plants used in phytotherapy, cosmetics and dyeing in the Pramanda district (North-West Greece) are reported. For many plants (myrtle, phlomis, daphne, etc.) the uses are localized and not noted for other phytotherapies; some uses coincide with those existing in other zones of the Mediterranean (mint, thyme, red juniper, Hypericum, etc.). The plants used are the most common and most easily found in this area.

Coloring Agents↗
PubMed1996

Antiviral activities of Nepalese medicinal plants.

In a screening of plants used traditionally in Nepal to treat diseases that could be caused by viruses, methanol extracts from 21 species were assayed for activity against three mammalian viruses: herpes simplex virus, Sindbis virus and poliovirus. Assays were performed in UV-A or visible light, as well as dark. Individual species of Hypericum, Lygodium, and Maesa exhibited impressive antiviral activities, although their selective effects on the three viruses suggested that the antiviral ingredients were different in each extract. In addition, many of the other extracts showed partial inactivation of one or more test viruses.

Animals↗
PubMed2006

A radioassay for synaptic core complex assembly: screening of herbal extracts for effectors.

Synaptic core complex formation between syntaxin and synaptosome-associated protein of 25 kDa (SNAP25) on the plasma membrane and synaptobrevin on the vesicle membrane is responsible for membrane fusion and neurotransmitter release. A radiolabeled protein binding assay for synaptic core complex formation was developed. The components of this assay included recombinant glutathione S-transferase (GST)-syntaxin immobilized on glutathione agarose beads, SNAP25 and (125)I-labeled synaptobrevin. Reactions were performed in tubes containing filter inserts to facilitate removal of unbound protein. The radiolabeled protein bound was then quantified by gamma counter. A K(d) of 1.6 microM was determined for the GST-syntaxin/SNAP25/synaptobrevin complex, and a K(d) of 12 microM was determined for the GST-syntaxin/synaptobrevin complex. The assay was used to screen 14 herbal extracts for effectors of core complex formation. Herbs traditionally used to treat neurological conditions such as depression, anxiety, and stress were chosen. A Hypericum perforatum extract was found to have a nonspecific effect via protein complexation, whereas an Albizzia julibrissin extract was found to reduce the level of core complex formation. The assay was used to further investigate the effect of the A. julibrissin extract. The discovery of an inhibitor of core complex formation demonstrates the efficacy of the assay in screening natural products for substances that affect core complex formation.

Animals↗