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PubMed1999

Biochemical activities of extracts from Hypericum perforatum L. 4th Communication: influence of different cultivation methods.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.), know since ancient times as medical plant, besides other activities such as wound healing, antighout, antirheumatic and diuretic properties, is used in the treatment of mild to moderate depression. Increasing application continuously makes cultivation under controlled conditions of Hypericum perforatum L. more important. This report shows the results of three-years cultivation experiments with Hypericum perforatum L. The findings indicate that N-fertilizing yields more plant material but results in a drug with less quantity of secondary metabolites. Important components of the drug were quantified by HPLC and their activities were analyzed with the aid of biochemical test systems. Narrowleaved and broadleaved varieties of Hypericum perforatum L. show differences both in activity and quality. In this experiments the most active extract was a methanolic extract derived from non-fertilized, broadleaved plants.

Anthracenes↗
PubMed1999

Hypericum perforatum extracts as potential antidepressants.

Extracts of Hypericum perforatum have been used in the treatment of mild to moderate depression for many years in Europe. More recently, these extracts have become available in the USA as dietary supplements and have been popularly used to improve mood. In support of this practice, data from several controlled clinical studies suggest that Hypericum perforatum is better than placebo and as effective as established antidepressant drugs. These data have, however, several limitations that should temper our enthusiasm and argue for more research before accepting Hypericum perforatum extracts into our pharmacopoeia of established antidepressants. Extant data on the possible effects of Hypericum perforatum extracts in depression are here critically reviewed and plans for further research presented.

Antidepressive Agents↗
PubMed1987

[Animal experiments on the psychotropic action of a Hypericum extract].

Extracts of Hypericum perforatum (Psychotonin M) (St. John's wort) with known concentrations of hypericin were tested in several models generally accepted as screening methods in experimental animal studies for the recognition of psychotropic, and in particular of antidepressant activity. Hypericum extract enhanced the exploratory activity of mice in a foreign environment, significantly prolonged the narcotic sleeping time dose-dependently, and within a narrow dose range exhibited reserpine antagonism. Similar to most other antidepressants, hypericum extract enhanced significantly the activity of mice in the water wheel test and after a prolonged daily administration decreased aggressiveness in socially isolated male mice. The presented data in addition to the already proven clinical efficacy justify the use of standardised Hypericum extract in the treatment of mild to moderate depression.

Aggression↗
PubMedDate not supplied

Phytochemical profiling of New and Old World Hypericum (St. John's Wort) species.

Botanical extracts of Hypericum perforatum L. (common St. John's Wort) are used in the USA and in Europe as a treatment for mild to moderate depression, although controversy surrounds the identity of the active constituent(s). RP-HPLC with photodiode array detection was used to separate and quantify nine compounds of pharmacological interest in extracts from 74 taxa of Hypericum native to the Old and New World. Chemical profiles of these constituents may be used to distinguish extracts of H. perforatum from those of other species of Hypericum, and to indicate species that may be of interest for further phytochemical investigation.

Geography↗
PubMed2004

Cytotoxic activity of Hypericum perforatum L. on K562 erythroleukemic cells: differential effects between methanolic extract and hypericin.

The influence of a methanolic extract of Hypericum perforatum L. and of purified hypericin has been comparatively tested on the growth of a human erythroleukemic cell line (K562). After 1 h exposure to increasing concentrations (as hypericin content) of both agents in the dark, leukemic cells were grown for 24 h and 48 h. The effects on cell growth were determined by viable cell count, flow cytometry analysis and fluorescence microscopy. Our data show that purified hypericin has only a weak inhibitory effect on cell growth and no effect in inducing apoptotic cell death. In contrast, the Hypericum flower extract shows a significant concentration-dependent and long-lasting inhibition of cell growth, and induces apoptotic cell death. This work con fi rms the interesting role of Hypericum perforatum L. in cancer therapy and strongly supports the hypothesis that agents, other than hypericin, present in the total extract can impair tumor cell growth acting separately or in a combined manner.

Anthracenes↗
PubMed2003

Hypericum perforatum attenuates nicotine withdrawal signs in mice.

RATIONALE: Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. OBJECTIVE: We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. METHODS: Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125-500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. RESULTS: The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. CONCLUSIONS: These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.

Animals↗
PubMed2002

Differential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers.

OBJECTIVE: We investigated the effects of treatment with Saint John's wort (hypericum perforatum) extract on the urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol in order to assess the effect of this extract on the activity of hepatic xenobiotic metabolizing enzymes. METHODS: Forty-eight healthy volunteers (25 male and 23 female) received a daily dose of 1800 mg hypericum extract for 14 days. Urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol was measured in 24-h urine samples on the day preceding the initiation of hypericum treatment and after 14 days of treatment. D-Glucaric acid was measured enzymatically. Cortisol and 6beta-hydroxycortisol were quantified using high-performance liquid chromatography with ultraviolet detection. RESULTS: Urinary excretion of D-glucaric acid was unaffected after a 14-day treatment with Saint John's wort extract (26.7 micromol/day vs 27.7 micromol/day; 95% confidence interval of the difference: -1.9 to 3.8). The urinary excretion of 6beta-hydroxycortisol increased from a mean baseline value of 254 microg/day to 369 microg/day (P<0.0001) indicating induction of CYP3A. While the excretion of free cortisol was unaltered, the ratio of 6beta-hydroxycortisol to free cortisol changed significantly from 9.9 at baseline to 14.3 (95% confidence interval of the difference: 2.3-6.5) after Saint John's wort treatment. CONCLUSIONS: High-dose treatment with Saint John's wort extract induced CYP3A activity in healthy volunteers as evidenced by increased 6beta-hydroxycortisol excretion. This enzyme induction most likely contributes to the decreased bioavailability observed upon co-administration of various drugs with Saint John's wort extract. The D-glucuronic acid pathway appeared unaffected by Saint John's wort.

Adult↗
PubMed2005

Compositions and antimicrobial activities of the essential oils of two Hypericum species from Turkey.

The chemical compositions of essential oils obtained from Hypericum hyssopifolium var. microcalycinum and Hypericum lysimachioides var. lysimachioides were analysed by using GC and GC-MS. Caryophyllene oxide was found to be the major component. The essential oils of both Hypericum species showed antimicrobial activity against nine microorganism at a concentration of 60 to 80 microg/ml.

Anti-Infective Agents↗
PubMed2004

Hypericum androsaemum infusion increases tert-butyl hydroperoxide-induced mice hepatotoxicity in vivo.

Increasing evidence regarding free radical generating agents indicates that the sustained production of high levels of reactive oxygen species (ROS) can cause hepatotoxicity. Being a short chain analog of lipid peroxide, tert-butyl hydroperoxide (t-BHP) is metabolized into free radical intermediates by cytochrome P450 in hepatocytes, which initiate lipid peroxidation, glutathione depletion and cell damage. The aim of the present study was to evaluate the putative protective effect of Hypericum androsaemum lyophilised infusion against t-BHP-induced mice hepatotoxicity in vivo, which has already been shown to be antioxidant in vitro. However, the results showed that the oral pretreatment with Hypericum androsaemum infusion (4, 20 and 100 mg/kg) for 4 days before a single intraperitoneal dose of t-BHP (1.8 mmol/kg) potentiated the t-BHP-induced hepatotoxicity. In fact, it was observed a potentiation in the depletion of total glutathione and reduced glutathione (GSH) contents and increase in oxidised glutathione (GSSG) level. Also the histopathological evaluation of the mice livers revealed that the infusion raised the incidence of liver lesions induced by t-BHP. These data do not corroborate any effect of Hypericum androsaemum infusion as hepatoprotector, but rather as a potentiator of hepatotoxicity in the present experimental conditions.

Animals↗
PubMed2005

Anticonvulsant effect of Hypericum perforatum: role of nitric oxide.

Hypericum perforatum L. is used in traditional medicine for its anticonvulsant property. We studied the anticonvulsant activity of the aqueous and ethanolic extracts of Hypericum perforatum aerial parts in mice in order to evaluate the traditional use of this plant. The pentylenetetrazole (PTZ) and the maximal electroshock seizure (MES) tests were used for assessing the anticonvulsive effects of this plant. In the PTZ test, the extracts (0.1-1g/kg, i.p.) delayed the onset of tonic convulsions and protected mice against mortality. In the MES test, both extracts did not showed an antiseizure activity. L-NAME (1-10 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, reduced the anticonvulsant activity of the extracts. The results of this study indicate that the extracts of Hypericum perforatum aerial parts could contribute to the control of petit mal seizure and this effect may be partially mediated by nitric oxide pathway.

Animals↗
PubMed2005

Large-scale observational studies of hypericum extracts in patients with depressive disorders--a systematic review.

We present a systematic review of observational studies of hypericum extracts in the treatment of depressive disorders. We included non-randomized studies with at least 100 patients suffering from depressive disorders treated with hypericum mono-preparations for at least 4 weeks, which reported clinical outcomes. Potentially relevant studies were identified through searches in electronic databases (Medline, PubMed), contacts with manufacturers, and handsearching of proceedings of phytomedicine congresses. Information on patients, interventions, methods an results were extracted by two reviewers. Sixteen studies including a total of 34,804 (range 101-11,296) patients met the inclusion criteria. Most studies investigated short-term effects (4-6 weeks) in patients with mild to moderate depression. Response rates (according to physician assessment) varied between 65% and 100%, the proportion of patients dropping out due to side effects varied between 0.0% and 2.8%. Two studies investigated long-term effects (52 weeks). Reponse rates were 60% and 69%, respectively, and the proportions of patients dropping out due to side effects were 3.4% and 5.7%, respectively. Serious side effects or interactions were not reported in any study. The quality of reporting was insufficient in the majority of publications. The available studies show that hypericum extract are well tolerated and seem to be effective in routine treatment of mild to moderate depressive disorders.

Antidepressive Agents↗
PubMed2004

Detection of hypericins in the "red glands" of Hypericum elodes by ESI-MS/MS.

The biologically active naphthodianthrones hypericin and pseudohypericin were detected by electrospray ionization mass spectrometry (ESI-MS/MS) in microsamples from the sepals of Hypericum elodes (Hypericaceae) containing the so-called "red glands", i.e. stipitate glands with red-coloured heads. The occurrence of hypericins in the red glands of H. elodes supports the taxonomic position of the section Elodes within the genus Hypericum and provides evidence that the ability of carrying out the biosynthetic pathway leading to the naphthodianthrone compounds, rather than the absolute amounts produced, should be regarded as a chemical marker of the phylogenetically more advanced sections of genus Hypericum. The biologically active phloroglucinol derivatives hyperforin and adhyperforin, so far found only in H. perforatum, were also detected and evidence for their localization in the sepal secretory canals with large lumen, is given.

Anthracenes↗
PubMed2005

Phytochemical analysis and genetic characterization of six Hypericum species from Serbia.

The secondary metabolite contents and genetic profiles of six Hypericum species (H. barbatum Jacq., H. hirsutum L., H. linarioides Bosse, H. maculatum Crantz, H. rumeliacum Boiss. and H. tetrapterum Fries), collected from different locations in Serbia, have been analyzed. Methanol extracts of the aerial parts of the plants were obtained by accelerated solvent extraction (ASE) at 40 degrees C and 100 bar, and analyzed for five pharmacologically important standard constituents (hyperoside, quercitrin, pseudohypericin, hyperforin and hypericin) by LC-MS/MS. The highest content of hypericin and pseudohypericin was observed in the H. barbatum extract, while the highest content of hyperforin and quercitrin was found in the H. tetrapterum extract and the highest content of hyperoside in the H. maculatum extract. A literature survey shows that the above six Hypericum species, with the exception of H. maculatum, have not been previously genetically profiled. In order to correlate the chemical constituents of the species under investigation with their genetic factors, genetic profiling of these species was undertaken using the random amplification of polymorphic DNA (RAPD) and single sequence repeat (SSR) profiles of the above selected plants. Among the 52 random primers used for the initial screening, only 10 yielded polymorphic RAPD profiles. A total of 111 polymorphic markers were generated using these primers. The SSR analysis shows that 8 out of the 10 primers used were polymorphic. The correlation among the species under investigation using the two genetic markers was performed using Jaccuard's coefficients of similarity and a high correlation (r=0.99) was obtained. The main conclusion from the above data is that there exists a stronger correlation for secondary metabolite contents with RAPD data than with SSR data among the six Hypericum species from Serbia.

Chromatography, Liquid↗
PubMed1998

Hyperforin as a possible antidepressant component of hypericum extracts.

We demonstrate that the phloroglucinol derivative hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure hyperforin. It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.

Animals↗
PubMed2000

Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation.

Immunosuppressive therapy in patients after liver transplantation requires careful monitoring of blood levels for immunosuppressive agents such as cyclosporin A. A variety of drugs are capable of interfering with the metabolism of cyclosporin A. We observed a 63-year-old patient who received a liver allograft for cryptogenic liver cirrhosis in 1998. This patient developed severe acute rejection 14 months after transplantation which was associated with a sudden drop in cyclosporin A levels. Two weeks previously, he had started taking the herbal drug Hypericum perforatum (2 x 900 mg/day) for increasing episodes of depression. The cyclosporin A dosage later had to be doubled, which caused some side effects. Finally, an assessment of oral cyclosporin A resorption suggested an enhanced cyclosporin A metabolism. Hypericum perforatum was stopped. Both cyclosporin A dosage and blood levels immediately returned to normal. The liver function recovered completely. In conclusion, this observation is a previously undescribed drug interaction of a widely used herbal drug (Hypericum perforatum, i.e. St. John's wort) in a patient after liver transplantation.

Antidepressive Agents↗
PubMed2002

Antimicrobial studies on three species of Hypericum from the Canary Islands.

The antimicrobial activity of several extracts and fractions of the aerial parts of Hypericum canariense, Hypericum glandulosum and Hypericum grandifolium was investigated using the disc diffusion and broth microdilution methods against twelve reference microorganisms (eight bacterial and four fungal strains). The methanol extract and chloroform fraction of H. canariense, as well as the methanol extracts, butanol and chloroform fractions of both H. glandulosum and H. grandifolium exhibited a good antibacterial activity against four Gram-positive bacteria (Bacillus cereus var. mycoides, Micrococcus luteus, Staphylococcus aureus and Staphylococcus epidermidis) and the Gram-negative bacterium Bordetella bronchiseptica with the diameters of growth inhibition area in the range 10-25 mm and MICs values between 0.03 and 0.29 mg/ml. Neither the infusions and aqueous fractions of the species studied nor the butanol fraction of H. canariense showed any antibacterial activity against the tested microorganisms. Amongst the active extracts, the minimum inhibitory concentration (MIC) determination showed that the H. canariense chloroform fraction was the most active against M. luteus, S. aureus and S. epidermidis. No antifungal activity was seen with any of the extracts or fractions tested. The results of this study support the use of these species in Canarian traditional medicine to treat skin infections.

Anti-Bacterial Agents↗
PubMed2003

The in vitro effects of Hypericum species on human leukocyte myeloperoxidase activity.

Myeloperoxidase (MPO) is a major component of the antimicrobial system of polymorphonuclear neutrophils. The heme enzyme MPO catalyzes the conversion of hydrogen peroxide and chloride to hypochlorous acid. Hypochlorous acid is the major strong oxidant produced by neutrophils and may contribute to inflammatory tissue damage. It was reported that certain antiinflammatory drugs are capable of inhibiting MPO activity and this inhibition may account for their antiinflammatory effect. Hypericum L. is a genus of about 400 species, widespread throughout the world. Some species of genus exhibit a significant antiinflammatory activity beside their several pharmacological properties such as antidepressant, diuretic, antihelmintic, and antibacterial. In this study, we investigated the in vitro effects of three Hypericum species, which exhibit antiinflammatory activity, on human polymorphonuclear leukocyte MPO activity. We found that each extract of Hypericum species reduced the peroxidative and chlorinating activity of human leukocyte MPO in concentration-dependent manner. The antiinflammatory activity of these species may be related with inhibition of MPO activity.

Anti-Inflammatory Agents↗
PubMed2001

Effect of Hypericum extract on the hypothalamic-pituitary-adrenal system in rats.

We studied the effect of Hypericum extract on activity of the hypothalamic-pituitary-adrenal system in rats. In rats exposed to stress after a 30-day daily oral treatment with Hypericum extract, the weight of the adrenals and ACTH concentration were lower than in controls. Hence, treatment with Hypericum extract improved resistance to stress and prevented exhausting of the hypothalamic-pituitary-adrenal system.

Adrenal Glands↗