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At least 703 records · Page 39Linked to original sources
PubMed2000

Potential use of medicinal plants in the treatment of alcoholism.

The present paper briefly reviews the most relevant experimental data on the reducing effect of some medicinal herbs on voluntary alcohol intake in animal models of alcoholism. Pueraria lobata, Tabernanthe iboga, Panax ginseng, Salvia miltiorrhiza and Hypericum perforatum proved to be effective in decreasing alcohol consumption. Reduction of alcohol absorption from the gastrointestinal system appears to be a common feature among most of the above plants. These data suggest that medicinal plants may constitute novel and effective pharmacotherapies for alcoholism.

Alcoholism↗
PubMed1999

Measurement of hyperforin a constituent of St. John's wort in plasma by high-performance liquid chromatography.

Hyperforin is a constituent of Hypericum perforatum extracts (St. John's wort, H. perforatum), which have antidepressant action. Hyperforin was extracted from plasma utilising a solid-phase extraction procedure. Chromatography was performed by isocratic reversed-phase high-performance liquid chromatography with UV end-point detection. The calibration curve was linear over the range 0.15-3 microg per ml of plasma. The sensitivity for hyperforin was 4.5 ng on-column. Mean inter- and intra-assay relative standard deviations over the range of the standard curve were less than 5%. The absolute recovery for hyperforin averaged 97.8%.

Animals↗
PubMed2001

Evaluation of chemical stability of St. John's wort commercial extract and some preparations.

Thermal and photostability of a commercial dried extract and capsules of St. John's wort (Hypericum perforatum L.) were evaluated under the ICH test conditions. The extract was considered as drug substance and its preparations as drug products. In addition, capsules of different colours corresponding to different opaficient and pigment contents were also evaluated as primary package of drug product and the tests in the secondary pack were performed with amber containers, as well. A selective high-performance liquid chromatography (HPLC) for determination of stability of all the characteristic constituents, namely flavonols, hyperforins and hypericins, was carried out. Photostability testing showed all the constituents to be photosensitive in the tested conditions. However, different opaficients and pigments present in the capsules influenced the stability of the different classes of constituents. Amber containers suggested as secondary packages influenced only in part the photostability of the investigated constituents. Long-term thermal stability testing showed a very low (less than 4 months) hyperforins and hypericins t(90), even if ascorbic and citric acids were added to the formulation. From the results we have obtained it is clear that for St. John's wort preparations, a mere translation of the ICH guidelines to the field of herbal products, as suggested by the WPHMP of the EMEA, cannot be accepted. A revision and adaptation of the storage conditions should be elaborated.

Capsules↗
PubMed2003

Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors.

Amentoflavone is found in a number of plants with medicinal properties, including Ginkgo biloba and Hypericum perforatum (St. John's Wort). We have developed a rapid and economic semi-synthetic preparation of amentoflavone from biflavones isolated from autumnal Ginkgo biloba leaves. Several studies have shown that amentoflavone binds to benzodiazepine receptors. Using two electrode voltage-clamp methodology, amentoflavone has been shown to be a negative modulator of GABA at GABA(A) alpha(1)beta(2)gamma(2L) receptors expressed in Xenopus laevis oocytes This action appears to be independent of the flumazenil-sensitive benzodiazepine modulatory sites on the GABA(A) receptor.

Animals↗
PubMed2003

Modulation of apoptosis in mice treated with Echinacea and St. John's wort.

Apoptosis, or programmed cell death (PCD), is a physiological active cellular suicide process that occurs in non-contiguous cells, and is usually not associated with inflammation. The apoptotic process can be modulated by various stimuli, including hormones, cytokines, growth factors, and some chemotherapeutic agents. To determine whether Echinacea purpurea and Hypericum perforatum are able to regulate the process of apoptosis in vivo and to define the role of the Fas-Ag and Bcl-2 signal transduction cascade, we have orally treated groups of mice with these vegetable drugs for 14 days. The splenic lymphocytes from mice treated with E. purpurea and H. perforatum at the two dose levels used (30 and 100 mg kg(-1) per day) were shown to be significantly more resistant to apoptosis than those from mice treated only with the vehicle. In addition, mice treated with the natural substances showed a decrease in Fas-Ag expression and an increase in Bcl-2 expression. In conclusion, our results shown that in vivo the studied drugs modulate apoptosis in mice splenic lymphocytes and that this action could be mediated in part by a decrease in Fas-Ag expression and in part by an increase in Bcl-2 expression.

Animals↗
PubMed2002

Hypericin in cancer treatment: more light on the way.

Photodynamic therapy (PDT) has been described as a promising new modality for the treatment of cancer. PDT involves the combination of a photosensitizing agent (photosensitizer), which is preferentially taken up and retained by tumor cells, and visible light of a wavelength matching the absorption spectrum of the drug. Each of these factors is harmless by itself, but when combined they ultimately produce, in the presence of oxygen, cytotoxic products that cause irreversible cellular damage and tumor destruction. Hypericin, a powerful naturally occurring photosensitizer, is found in Hypericum perforatum plants, commonly known as St. John's wort. In recent years increased interest in hypericin as a potential clinical anticancer agent has arisen since several studies established its powerful in vivo and in vitro antineoplastic activity upon irradiation. Investigations of the molecular mechanisms underlying hypericin photocytotoxicity in cancer cells have revealed that this photosensitizer can induce both apoptosis and necrosis in a concentration and light dose-dependent fashion. Moreover, PDT with hypericin results in the activation of multiple pathways that can either promote or counteract the cell death program. This review focuses on the more recent advances in the use of hypericin as a photodynamic agent and discusses the current knowledge on the signaling pathways underlying its photocytotoxic action.

Anthracenes↗
PubMedDate not supplied

St. John's wort and oral contraceptives: reasons for concern?

St. John's wort (Hypericum perforatum) is one of the best-selling herbal remedies in the United States. It has been implicated as an inducer of the P450 enzyme system, and as such, may cause increased metabolism of certain drugs, including oral contraceptives. Women using oral contraceptives have been warned against using St. John's wort. To date, there are some case reports but little clinical data demonstrating risk of contraceptive failure if they do. This article reviews available data and discusses theoretical reasons for concern about possible drug-herb interactions.

Contraceptives, Oral↗
PubMed2006

Nasal insertion of St John's wort: an unusual cause of epistaxis.

We report a case of severe unilateral epistaxis requiring surgical arrest of bleeding, via endoscopic sphenopalatine artery ligation and anterior ethmoidal artery ligation. This followed recreational nasal insertion of St John's wort (Hypericum perforatum). Interactions between this substance and prescribed drugs have been described following oral ingestion. However, this unusual case highlights a further, worrying potential rhinological side effect of this substance.

Administration, Intranasal↗
PubMed2000

Efficacy and safety of St. John's wort for the treatment of major depression.

OBJECTIVE: Extracts of St. John's wort have been widely used in the treatment of depression. Our aim was to review information related to the efficacy and safety of St. John's wort as an antidepressant. DATA SOURCES: Primary and review articles were identified by a search of Medline (1960 to February 2000) and through secondary sources. STUDY SELECTION: All the articles identified from the data sources were evaluated and all relevant information was included in this review. The pharmacokinetics, mechanism of action, efficacy, side effects and drug interactions of St. John's wort have been examined in various studies. CONCLUSION: St. John's wort is a promising investigational antidepressant, but the data are not yet sufficient to accept hypericum as a first line antidepressant preparation for treatment of depression. Besides the need for dose standardization and adequate trial lengths, there is a need for studies in severely depressed patients and long-term studies to assess the risk of relapse and recurrence.

Antidepressive Agents↗
PubMed2003

Simple detection method of powerful antiradical compounds in the raw extract of plants and its application for the identification of antiradical plant constituents.

A simple detection method for a powerful radical scavenging compound in a mixture containing a large variety of compounds, such as the raw extract of edible plants, was developed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) as the radical reagent. The method was established on the basis of the features of the typical chain-breaking antioxidation reaction mechanism, which suggests that the radical scavenging antioxidant should be converted to other stable nonradical compounds during the reaction. This method requires only a simple HPLC instrument, and the disappearance or decrease in the peak intensity, which is induced by the addition of DPPH. This change is monitored by the HPLC to detect the powerful radical scavenger from the complex mixture. The method was applied to the detection and identification of the most powerful antiradical compound in the extracts of three antioxidatively active plant extracts (Psidium guajava, Citrus depressa, and Hypericum chinense). The radical scavenging efficiency of a newly identified compound from H. chinense was also compared with that of Trolox and catechin using the method.

Antioxidants↗
PubMed2003

Hyperatomarin, an antibacterial prenylated phloroglucinol from Hypericumatomarium ssp. degenii.

As shown by quantitative (1)H NMR measurements, a lipophilic extract of the aerial parts of Hypericum atomarium ssp. degenii contained a high percentage (3.1% per weight of dried plant material) of a prenylated phloroglucinol (1). Compound 1, named hyperatomarin, occurring in two tautomeric forms (1a <==> 1b), was isolated by bioactivity-guided preparative TLC and was identified on the basis of spectral data interpretation. This isolated phloroglucinol exhibited activity against Gram-positive (Staphyloccocus aureus and Microccocus luteus) and Gram-positive spore-forming bacteria (Bacillus subtilis and B. IP 5832).

Anti-Infective Agents↗
PubMed2006

p27(SJ), a novel protein in St John's Wort, that suppresses expression of HIV-1 genome.

Transcription of the HIV-1 genome is controlled by the cooperation of viral regulatory proteins and several host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, (LTR). Here, we describe the identification of a novel protein, p27(SJ), present in a laboratory callus culture of Hypericum perforatum (St John's Wort) that suppresses transcription of the HIV-1 genome in several human cell types including primary culture of microglia and astrocytes. p27(SJ) associates with C/EBPbeta, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27(SJ) with C/EBPbeta and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27(SJ) forces its entry into the nucleus and diminishes the capacity of p27(SJ) to suppress Tat activity, but does not alter its ability to suppress C/EBPbeta activation of the LTR. Results from binding assays showed the inhibitory effect of p27(SJ) on C/EBPbeta interaction with DNA. Finally, our results demonstrate that expression of p27(SJ) decreases the level of viral replication in HIV-1-infected cells. These observations suggest the potential for the development of a therapeutic advance based on p27(SJ) protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.

Astrocytes↗
PubMed2006

Hyperforin prevents beta-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-beta-deposits.

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (Abeta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Abeta-induced spatial memory impairments and on Abeta neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Abeta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Abeta oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Abeta aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.

Alzheimer Disease↗
PubMed2002

The effects of St John's wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men.

AIMS: To compare the effects of multiple dosing with St John's wort (Hypericum perforatum) extract and amitriptyline on heart rate variability, cognitive function and quantitative EEG (qEEG) with placebo in healthy humans. METHODS: A randomized, double-blind, cross over study of 12 healthy male volunteers. Subjects orally received capsules with 255-285 mg St John's wort extract (900 micro g hypericin content), 25 mg amitriptyline and placebo three times daily for periods of 14 days each with at least 14 days between. The doses of amitriptyline and St John's wort extract are comparable with respect to their antidepressant activity. Compliance was confirmed by coadministration of 10 mg of riboflavin with each capsule and detection of urinary vitamin B2 on treatment day 11 with high performance liquid chromatography. Measurements of heart rate variability, psychometric tests and qEEG were performed before start of medication and repeatedly on the last treatment day. RESULTS: St John's wort extract did not affect heart rate variability (HRV) whereas amitripytline significantly decreased it: the difference in the percentage number of adjacent RR intervals> 50 ms (pNN50) was 8.6 (-2.6, 19.9; mean; 95% confidence interval) between St John's wort extract and placebo and -17.6 (-24.7, -10.4) between amitriptyline and placebo. Neither St John's wort extract nor amitriptyline had an influence on cognitive performance such as choice reaction, psychomotor coordination, short-term memory and responsiveness to distractive stimuli. Amitriptyline but not St John's wort extract decreased self rated activity (P < 0.05). Both drugs caused significant qEEG changes. St John's wort extract increased theta power density. Amitriptyline increased theta as well as fast alpha power density. CONCLUSIONS: Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.

Adult↗
PubMed2001

Comparison of the effects of an alcoholic St. John's wort extract on various isolated organs.

We have studied the effects of a St. John's wort extract used in therapy on contractions of various isolated organ preparations induced by diverse spasmogens. Although it nonspecifically antagonized guinea pig ileum contractions induced by 7 different spasmogens, it had no effect on depolarization-induced contractions of rat aorta or those induced by acetylcholine, histamine or serotonin in the guinea-pig trachea. Spontaneous rhythmic contractions of rat portal veins were also not affected by the extract. Serotonin-induced contractions of rat aorta were most effectively inhibited by the agent. The observed effects of the extract were more prominent after it was washed out of the organ bath. Surprisingly, however, the extract also exerted negative inotropic and chronotropic effects on the rat atrium preparation. Our observations revealed several pharmacological properties of the Hypericum extract, and thus could be helpful in identifying and characterizing its active components and their modes of action.

Alcohols↗
PubMed2001

Evaluation of synaptosomal uptake inhibition of most relevant constituents of St. John's wort.

In our previous investigations, we could demonstrate that extract preparations of Hypericum perforatum (St. John's wort, SJW) inhibit the uptake of several neurotransmitters (serotonin, norepinephrine, dopamine, GABA, L-glutamate) in synaptosomal preparations of rodent brain. Hyperforin, the lipophilic constituent, was identified as the main component responsible for these effects. The properties seen for hyperforin in these and other pharmacological models present a plausible and logical explanation for the well documented antidepressive effects of SJW extract preparations in clinical studies. However, evidence for other active principles in SJW extract have been reported (See also communications by Misane & Ogren and Philippu in this issue). Accordingly, we tested various SJW extract preparations and all relevant constituents as possible inhibitors of synaptosomal uptake of neurotransmitters. Two further components were found to be active in those models. Adhyperforin, like hyperforin, showed a strong inhibiting profile in all uptake systems investigated. Moreover, we could observe a weak to moderate inhibiting profile for the oligomeric procyanidins fraction (OPC). Further investigations would have to clarify any possible contribution of these two constituents to the antidepressive effects of SJW extract seen in animal experiments and clinical trials.

Animals↗
PubMed2001

Neurochemical studies with St. John's wort in vitro.

The effect of extracts and constituents of St. John's wort, Hypericum perforatum, at various CNS receptors were studied by radioligand binding techniques in order to determine a profile of pharmacological activity in vitro. Binding inhibition was examined for the G-protein coupled opioid, serotonin (5-HT), histamine, neurokinin and corticotropin releasing factor (CRF) receptors, for the steroid estrogen-alpha receptor and for the ligand-gated ionchannel GABA(A) receptor. Hypericin showed the most potent binding inhibiton of all tested constituents to human CRF1 receptor with an IC50 value of 300 nM. Preliminary GTPgamma35S binding studies to CRF1 coupled G-protein indicated an antagonistic action for hypericin. The acylphloroglucinole hyperforin failed to inhibit 125I-astressin binding to hCRF, receptor up to 10 microM. Hyperforin inhibited binding to opioid and serotonin (5-HT) receptors at IC50 values between 0.4 and 3 microM, while hypericin and pseudohypericin inhibited with weaker potency. The biflavonoid I3,II8-biapigenin inhibited 3H-estradiol binding to the estrogen-alpha receptor with an IC50 value of 1 microM. The inhibition of 3H-muscimol binding to the GABA(A) receptor is likely to be exclusively due to GABA present in the extract. We therefore hypothesize that additive or synergistic actions of several ditsinct compounds may be responsible for the beneficial antidepressant effect of St. John's wort.

Animals↗
PubMed2003

In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine.

Miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is one of the flavonoids of St. John's wort (Hypericum perforatum L.) whose antidepressant activity has been shown by the forced swimming test, an in vivo pharmacological model with rats. However, nothing is known about its ability to reach the CNS after oral administration. We examined the pathway of miquelianin from the small intestine to the central nervous system using three in vitro membrane barrier cell systems. In the Caco-2 cell line, miquelianin showed a higher uptake (1.93 +/- 0.9 pmol x min(-1) x cm(-2)) than hyperoside (quercetin 3-O-beta-D-galactopyranoside; 0.55 +/- 0.18 pmol x min(-1) x cm(-2)) and quercitrin (quercetin 3-O-alpha-L-rhamnopyranoside; 0.22 +/- 0.08 pmol x min(-1) x cm(-2)). The permeability coefficient of miquelianin (Pc = 0.4 +/- 0.19 x 10(-6) cm/sec) was in the range of orally available drugs assuming sufficient absorption from the small intestine. Uptake and permeability of the examined compounds was increased by the MRP-2 inhibitor MK-571 indicating a backwards transport by this membrane protein. Porcine cell cultures of brain capillary endothelial cells were used as a model of the blood-brain barrier (bbb) and epithelial cells of the plexus chorioidei as a model of the blood-CSF barrier (bcb). Results indicate no active transport in one direction. Although moderate, the permeability coefficients (bbb: Pc = 1.34 +/- 0.05 x 10(-6) cm/sec; bcb: Pc = 2.0 +/- 0.33 x 10(-6) cm/sec) indicate the ability of miquelianin to cross both barriers to finally reach the CNS.

Administration, Oral↗