Hypericum Perforatum Extract Research Articles

Hypericum perforatum extracts as potential antidepressants

Hypericum perforatum extracts as potential antidepressants

Determination of phenolic compounds in medicinal herbs by reversed-phase HPLC

An HPLC procedure is proposed for the determination of 12 phenolic compounds in plant tissues by reversed-phase HPLC with gradient elution and UV detection. The influence of pH, composition of the mobile phase, concentration of the organic modifier, and temperature on the separation of gallic, protocatechuic, trans-ferulic, trans-caffeic acid, rutin, quercetin, dihydroquercetin, and (_)-epicatechin for 30 min is studied. The lower limit of quantification of phenolic compounds is 1–2.5 μg/L. The procedure was applied to the determination of phenolic compounds in aqueous extracts of Hypericum perforatum; its sample was found to contain protocatechuic acid, (_)-epicatechin, and also rutin.

Effect of residual distillation water of 15 plants and three plant hormones on Scotch spearmint ( Mentha × gracilis Sole)

Distillation waste water is a byproduct from steam distillation of aromatic crops, and is currently discharged into streams and rivers. We evaluated distillation waste water (extract) from 15 essential oil crops plus three plant hormones (methyl jasmonate, MJ; gibberellic acid, GA3; and salicylic acid, SA) as foliar spray for Scotch spearmint ( Mentha × gracilis Sole). GA3 and Achillea millefolium extract decreased essential oil content. Hypericum perforatum extract increased α-pinene, whereas SA decreased it. H. perforatum extract increased β-pinene and sabinene concentrations relative to hormones but was not different from the control. H. perforatum also increased l-limonene, while SA and GA3 decreased myrcene and MJ and SA decreased l-limonene. Application of MJ and SA increased l-carvone concentration relative to the control and most other treatments. The sulfur concentration in plant extracts was positively correlated to β-caryophyllene. None of the residual distillation waters showed significant antimicrobial or antimalarial activity. The distillation waste water from essential oil crops may serve as a modifier for Scotch spearmint essential oil.

Potential of St John's Wort for the Treatment of Depression: The Economic Perspective

The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content. As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.

Isolation and purification of series bioactive components from Hypericum perforatum L. by counter-current chromatography

Counter-current chromatography (CCC) combined with pre-separation by ultrasonic solvent extraction was successively used for the separation of series bioactive compounds from the crude extract of Hypericum perforatum L. The petroleum ether extract was separated by the solvent system of n-heptane–methanol–acetonitrile (1.5:0.5:0.5, v/v) and n-heptane–methanol (1.5:1, v/v) in gradient elution, yielding a phloroglucinol compound, hyperforin with HPLC purity over 98%. The ethyl acetate extract was separated by using the solvent system composed of hexane–ethyl acetate–methanol–water (1:1:1:1 and 1:3:1:3, v/v) in gradient through both reverse phase and normal phase elution mode, yielding a naphthodianthrone compound, hypericin with HPLC purity about 95%. The n-butanol extract was separated with the solvent system composed of n-butanol–ethyl acetate–water (1:4:5 and 1.5:3.5:5, v/v) in elution and back-extrusion mode, yielding two of flavones, rutin and hyperoside, with HPLC purity over 95%. HPLC–MS, reference sample and UV spectrum were selectively used in separation to search for target compounds from HPLC-DAD profiles of different sub-extracts. The structures of isolated compounds were further identified by ESI-MS, 1HNMR and 13CNMR.

Effects of Hypericum perforatum extract on rat irritable bowel syndrome.

Context:In irritable bowel syndrome (IBS), disturbance of bowel motility is associated with infiltration of inflammatory mediators and cytokines into the intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa (TNF-α), and lipid peroxide.Aims:Regarding promising anti-inflammatory and anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti-depressant effect, this study was designed to evaluate the effects of HP in an experimental model of IBS.Settings and Design:IBS was induced by a 5-day restraint stress in rats. The HP extract was administered by gavage in doses of 150, 300, and 450 mg/kg for 26 days. Fluoxetine and loperamide were used as positive controls. Gastric emptying and small bowel and colon transit, besides the levels of TNF-α, MPO, lipid peroxidation, and antioxidant power, were determined in colon homogenates.Statistical Analysis Used:Data were analyzed by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons.Results:A significant reduction in small bowel and colonic transit (450 mg/kg), TNF-α, MPO, and lipid peroxidation and an increase in antioxidant power in all HP-treated groups (150, 300, and 450 mg/kg) were seen as compared with the control group. Gastric emptying did not alter significantly when compared with the control group. Treatment with loperamide (10 mg/kg) significantly inhibited gastric emptying and small bowel and colonic transit, while flouxetine (10 mg/kg) decreased gastric emptying, TNF-α, MPO, and lipid peroxidation and increased the antioxidant power of the samples in comparison with the control group.Conclusions:HP diminished the recruitment of inflammatory cells and TNF-α following restraint stress not in a dose-dependent manner, possibly via inhibition of MPO activity and increasing colon antioxidant power, without any difference with fluoxetine. The HP extract inhibits small bowel and colonic transit acceleration like loperamide but has minimal effect on gastric emptying.

Phenolic content, antioxidant and antifungal activities of acetonic, ethanolic and petroleum ether extracts of Hypericum perforatum L.

The objective of this study was to evaluate antifungal and antioxidant activities of Hypericum perforatum L. extracts against the growth of certain fungi. The ethanolic, acetonic and petroleum ether extracts of the plant were evaluated for phenols, flavonoids and non-flavonoids. The highest amounts of phenols (17.6 mg EPC/g dry extract) and flavonoids (16.85 mg EPC/g dry extract) were found in the acetonic extract. The highest inhibitory effect on the growth of Penicillium canescens, Fusarium oxysporum, Alternaria alternata, Aspergillus glaucus and Phialophora fastigiata by the disk diffusion method was exhibited by the ethanolic extract at the concentration of 25 mg/disk. The minimum inhibitory concentration (MIC) of the ethanolic and petroleum ether extracts was 20 mg/mL. The acetonic extract did not affect the growth of the tested fungi. Antioxidant activity was assessed by determining 1,1-Diphenyl-2-picryl-hydrazyl-hydrate (DPPH) free radical scavenging activity. The results showed that the ethanolic extract of Hypericum perforatum L. possesses antioxidant activity. The IC50 values, defined as the concentration of the test sample leading to 50% reduction of the free radical concentration, determined for each measurement were <7.8125, 105.9, 5.99 and 12.77 ?g/ml for the ethanolic extract, the acetonic extract, ascorbic acid and BHT, respectively, for DPPH free radical scavenging activity.

The Study of Hypericum perforatum extract on wound healing in rabbit

Wound healing is a natural reaction to injury witch results in restoration of tissue integrity. Repair consists of four phases: inflammation, re-epithelialization, angiogenesis, fibroblast recruitment and scarring. In this study the healig effect of Hypericum perforatum extract was investigated on open wound. Hydroalcoholic extract of Hypericum P. was prepared by maceration method. Newzeland rabbits of either sexes weighting 1.6-2.5 kg were used. Method of Cross et al (1995) was used to perform excisional wound. Hairs of lower back and left flank of animal was carefully shaved and cleaned. Animal was held in standard crouching position. A template measuring 20×20 mm was placed on the skin and the outline traced using a fixed-tipped pen. Desired area was locally anasthetised with lidocaine 2%. Full thickness wound was made by excising the skin using a scalped blade and forceps. Every day the outline of each wound was traced by using a transparent plastic sheet. Treatment of wounds started from the first moments, twice daily. In other to minimize the errors, measurment was repeated three times. Then area of wounds was calculated by mm chart paper. Wound of bland group were left untreated. Second group was treated with eucerin as placebo control, in third group phenytion cream 1% was used as standard control and in other groups different concentration of hypericum extract 2%, 5%, and 10% w/w in eucerin base were adminstrated twice daily. Area of wound in the first day was considerd as 100% and area of subequent days were compared with initial day. Percentage of healing was calculared by substracting the percentage of area from 100. Healing of eucerin and phenytoin groups lasted 21 and 158 day respectively. Healing in Hypericum cream of 2%, 5% and 10% groups lasted 14, 15 and 16 days respectively. Best results obtained with 2% extract. The result of this study confirms that Hypericum cream 2% had the best wound healing effect even better than phenytion cream, however the Hypericum Cream 5% & 10% had good and noticeable effect too.

Bioactive xanthones from the roots of Hypericum perforatum (common St John's wort).

Extracts of Hypericum perforatum L. (common St John's wort; Hypericaceae) are sold as phytopharmaceuticals and herbal supplements to treat mild to moderate depression and as food additives. Extensively cultivated in Europe, plants can be infected by anthracnose (Colletotrichum gloeosporioides), a virulent fungal pathogen that causes tissue necrosis and dramatically decreases crop value. Such infections triggered the production of new secondary metabolites, specifically xanthones, in cell culture experiments. Bioassay-guided fractionation of H. perforatum root extracts, testing for growth inhibition of plant pathogenic fungi from the genera Colletotrichum, Botrytis, Fusarium and Phomopsis, was performed. In vitro anti-inflammatory activity through inhibition of COX-1, COX-2 and 5-LOX-catalyzed LTB(4) formation was also evaluated. Extracts were analyzed by various chromatographic means and structure elucidation was performed using data from nuclear magnetic resonance and mass spectrometry. Researchers have previously described constituents from the aerial parts of this species, but few reports describe secondary metabolites found in underground parts, of particular interest because the lower stem and upper root are often sites of fungal infection. This work resulted in the isolation of three xanthones: 1,6-dihydroxy-5-methoxy-4',5'-dihydro-4',4',5'-trimethylfurano-(2',3':3,4)-xanthone; 4,6-dihydroxy-2,3-dimethoxyxanthone; and cis-kielcorin, one of which possessed novel bioactivity against species of Phomopsis and inhibited 5-LOX-mediated LTB(4) formation.

Gastroprotective activity of Hypericum perforatum extracts prepared with different vegetable oils

Gastroprotective activity of Hypericum perforatum extracts prepared with different vegetable oils

Inhibition of 17β-estradiol activation by CYP1A1: Genotype- and regioselective inhibition by St. John's Wort and several natural polyphenols

Several epidemiological studies associate certain CYP1A1 genotypes, alone or in combination, with an increased risk of estrogen-related cancers. Previously we demonstrated that metabolic activation of estrogens by CYP1A1 is a genotype-dependent reaction with the CYP1A1.2 (Ile462Val) variant being the most efficient catalyst (Kisselev et al.). To answer the question whether genotype-dependent inhibition of activation of estrogens by CYP1A1 could also contribute, we studied the inhibition of hydroxylation activity of the most common allelic variants of human CYP1A1 towards 17β-estradiol. We expressed and purified CYP1A1.1 (wild-type), CYP1A1.2 (Ile462Val), and CYP1A1.4 (Thr461Asn) and performed inhibition assays by natural polyphenols of our diet and drugs of NADPH-dependent estradiol hydroxylation in reconstituted CYP1A1 systems. From the polyphenols studied, a St. John's Wort ( Hypericum perforatum) extract, some of its main single constituents hypericin, pseudohypericin, and quercetin, as well as the flavonols kaempferol, myricetin and the phytoestrogens resveratrol and tetramethyl-stilbene exhibited strong inhibition. For the St. John's Wort extract and its single constituents hypericin, pseudohypericin, and quercetin, inhibition exhibited a remarkable dependency on the CYP1A1 genotype. Whereas (wild-type) CYP1A1.1 was most inhibited by the whole crude extract, the variant CYP1A1.2 (Ile462Val) was significantly stronger inhibited by the constituents in its pure form: IC 50 values for 2-hydroxylation was more than two times lower compared with the wild-type enzyme and the variant CYP1A1.4 (Thr461Asn). Besides this, the inhibition exhibited a remarkable regioselectivity. The data suggest that risk of estrogen-mediated diseases might be not only influenced by CYP1A1 genotype-dependent activation but also its inhibition by natural polyphenols of our diet and drugs.

Effects of Hypericum perforatum extract on diabetes‐induced learning and memory impairment in rats

Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin-induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients.

Hypericum perforatum extract is as efficacious as imipramine for moderately depressed patients

Hypericum perforatum extract is as efficacious as imipramine for moderately depressed patients

Identification of JAK–STAT pathways as important for the anti-inflammatory activity of a Hypericum perforatum fraction and bioactive constituents in RAW 264.7 mouse macrophages

Hypericum perforatum extracts have been used to treat diseases, including mild-to-moderate depression and inflammatory conditions. It is particularly important to identify which constituents present in the H. perforatum extracts are responsible for its anti-inflammatory activity since consumers are taking H. perforatum preparations to treat inflammation. We used a combination of four putative bioactive constituents, called the 4-component-system that interacted synergistically to explain the light-activated anti-inflammatory activity of an H. perforatum fraction in RAW 264.7 mouse macrophages. We also combined the constituents at concentrations detected in the fraction to identify key molecular targets. LPS was used to model an inflammatory response, and the 4-component-system and H. perforatum fraction were used as treatments that inhibited LPS-induced prostaglandin E 2 (PGE 2) production in RAW 264.7 mouse macrophages in the studies of gene expression profiles. We used Affymetrix genechips, statistical analysis, and quantitative real-time PCR to identify key gene targets of the 4-component-system and the sub-fraction from an H. perforatum ethanol extract. The H. perforatum sub-fraction, with or without LPS stimulation, affected far more genes than the 4-component-system with and without LPS. Genes involved in Janus kinase, as well as a signal transducer and activator of transcription (JAK–STAT) and eicosanoid pathways were identified that could account for the reduction in PGE 2 observed with both treatments in LPS-stimulated macrophages. Ten genes may be particularly important targets for activity of the 4-component-system and the fraction with LPS stimulation and these genes were involved in inflammatory signaling pathways, namely the JAK–STAT and eicosanoid pathways.

A Semiquantitative FIA-ESI-MS Method for the Rapid Screening of Hypericum perforatum Crude Extracts

A method based on FIA-ESI-MS has been developed to profile the major constituents of Hypericum perforatum extracts. The objective was to obtain simultaneous semi-quantitative data on hypericin, chlorogenic acid, rutin, quercitrin, quercetin and hyperforin contents for a high-throughput screening of the raw plant material. The principal drawback of FIA-ESI analysis of complex mixtures involves ion suppression effects: the ionization of some components of the mixture can be severely suppressed by ionization of others. The results show that this problem can be alleviated using a new approach to generate calibration curves.

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.

Isolation, purity analysis and stability of hyperforin as a standard material from Hypericum perforatum L.

In 1996 131.5 million daily doses of preparations containing extracts of Hypericum perforatum L. were prescribed in Germany for treating mild to moderately severe depressive disorders. New pharmacological and clinical results focus on hyperforin as the main active ingredient of the drug. Hyperforin (C35H52O4) is one of the main components (2-4%) of the dried herb Hypericum perforatum L. It was isolated after six consecutive steps: extraction of deep-frozen blossoms (-20 degrees C) with n-hexane by means of an Ultra Turrax at room temperature; separation of lipophilic substances on a silica gel column; purification of the relevant fraction by preparative HPLC; evaporation of the mobile phase under reduced pressure; removal of the remaining water by freeze-drying; and storage of hyperforin at -20 degrees C under nitrogen. The identity and purity of the isolated substance were determined by high-performance thin-layer chromatography (HPTLC), high-performance liquid chromatography (HPLC) with diode-array and ultraviolet detection (DAD and UV), Fourier-transformed infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopy, and liquid chromatography coupled with positive-ion electrospray-ionization tandem mass spectrometry (LC-ESI(+)-MS-MS). By use of these methods the purity of hyperforin was shown to be >99.9%. Peroxides present at each step of the isolation were detected by titration and by means of Merckoquant analytical peroxide test-strips. Elimination of the peroxides and stabilization of hyperforin was achieved by consistent protection from oxidation-the mobile phases were protected by use of ascorbic acid; evaporation and freeze-drying were performed under nitrogen; and the mobile phase used for preparative HPLC was sparged with helium. Stability testing was performed by HPLC-the samples were stored at -30 degrees C in a normal atmosphere and at -20, 4, and 20 degrees C in a normal atmosphere or under nitrogen. Results were compared with those obtained after storage under liquid nitrogen (-196 degrees C). Because of its high sensitivity to oxidation, hyperforin was more stable under nitrogen under all test conditions. There was no statistically significant difference between results obtained after 8 months at -20 degrees C under nitrogen or at -30 degrees C under a normal atmosphere and those from the reference sample stored under liquid nitrogen (-196 degrees C). Despite this, because of the tendency of hyperforin to degrade, long-term storage at -70 degrees C under nitrogen is recommended.

Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice

The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [(3)H]serotonin uptake in mice with little effect on specific [(3)H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [(3)H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant K(i) value for [(3)H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg(-1)), paroxetine (1 mg kg(-1)) and sertraline (10 mg kg(-1)) brought about significant increases in the K(m) value for [(3)H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [(3)H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [(3)H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort.

A Hypericum Extract in the Treatment of Depressive Symptoms in Outpatients: An Open Study

Background: Extracts of Hypericum perforatum have demonstrated in randomized trials (RCTs) to be effective in mild to moderate depressive episodes. However, as their use in daily practice may differ from that in RCTs we have conducted a study to achieve a better estimate of the range and frequency of adverse drug reactions (ADR) and the efficacy. Patients and Methods: In an observational study in Germany, adult outpatients with depressive syndrome were treated with an extract of St. John’s Wort. Study duration was 12 weeks, with control visits every 4 weeks. Besides anamnestic data, the variables assessed were: evolution of ICD-10 derived symptom score, Global Clinical Impression scale (GCI), and tolerability. Results: 1,778 patients from 304 centers participated in the study (mean duration of disorder 7.3 ± 18.9 months), and 1,541 patients completed it. At the last control visit the ICD-10 sum score had dropped by 63.1% and the proportion of patients described as ‘normal to mildly ill’ (GCI-s) had increased from 21.6% at admission to 72.4%. Regarding the GCI-i, 77% of the patients had improved ‘very much’ or ‘much’ at the last visit. This was consistent with their self-assessment (76%). Lower age and shorter duration of the disorder were associated with significantly better outcomes. The incidence of ADRs was 3.54% and had been decreasing continuously from the first control visit onwards; serious ADRs did not occure. Conclusions: The herbal drug was well tolerated, and no new or serious ADR were identified. In view of the limitations inherent to the study design, it can be concluded that extracts of St. John’s Wort are effective as an antidepressant in the management of depression in daily practice.

In vitro anti-hepatitis B virus effect of Hypericum perforatum L.

The anti-hepatitis B virus (HBV) effects and its mechanisms of the ethanol extracts of Hypericum perforatum L. (EHP) in vitro were explored. HepG2 2.2.15 cells, a stable HBV-producing cell line, were cultured as the model system to observe the anti-HBV effect. The viral antigens of cellular secretion, HBsAg and HBeAg, were determined by enzyme linked immunosorbent assay (ELISA). The quantity of HBV-DNA released in the supernatant was assayed by real-time PCR. In order to understand the mechanisms of the suppression of HBV replication, all HBV promoters (Cp, Xp, S1p, S2p and Fp) with luciferase reporter gene were transfected into HepG2 cells respectively. Then the activities of viral promoters were examined by luciferase reporter assay. It was found EHP effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose-dependent manner, as well as the extracellular HBV DNA. And EHP could selectively inhibit the activity of HBV promoter Fp. Our data suggest that EHP exerts anti-HBV effects via inhibition of HBV transcription, which helps to elucidate the mechanism underlying the potential therapeutic value of EHP.