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PubMed2004

Drug interactions with St John's wort : mechanisms and clinical implications.

The purpose of this paper is to review preclinical and clinical evidence relating to drug interactions with preparations of the medicinal herb St John's wort (Hypericum perforatum). A systematic literature search was carried out in three electronic databases up to June 2004. Information about case reports classified as St John's wort drug interactions was retrieved from the WHO Collaborating Centre for International Drug Monitoring and from the UK Medicines and Healthcare products Regulatory Agency in June 2003. Against the background of proven efficacy in mild to moderate depressive disorders and an excellent tolerability profile in monotherapy, there is sufficient evidence from interaction studies and case reports to suggest that St John's wort may induce the cytochrome P450 (CYP) 3A4 enzyme system and the P-glycoprotein drug transporter in a clinically relevant manner, thereby reducing efficacy of co-medications. Drugs most prominently affected and contraindicated for concomitant use with St John's wort are metabolised via both CYP3A4 and P-glycoprotein pathways, including HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors (only CYP3A4), the immunosuppressants ciclosporin and tacrolimus, and the antineoplastic agents irinotecan and imatinib mesylate. Efficacy of hormonal contraceptives may be impaired as reflected by case reports of irregular bleedings and unwanted pregnancies. Drugs with a narrow therapeutic index should be monitored more closely when St John's wort is added, discontinued or the dosage is changed. The St John's wort constituent hyperforin is probably responsible for CYP3A4 induction via activation of a nuclear steroid/pregnane and xenobiotic receptor (SXR/PXR) and hypericin may be assumed to be the P-glycoprotein inducing compound, although the available evidence is less convincing. Combinations of St John's wort with serotonergic agents and other antidepressants should be restricted to prescription-only, by experienced clinicians, due to potential central pharmacodynamic interactions. In conclusion, providing certain precautions and contraindications are followed, and adequate information is given to healthcare professionals and patients, the safe and effective use of quality-tested St John's wort products can be ensured.

Animals↗
PubMed2000

St John's wort: a potential therapy for elderly depressed patients?

St John's wort (Hypericum perforatum) has a 2000-year history of use as a medicinal herb. Its modern application as a plant extract for treating depression has undergone scientific investigation over the last decade, and its effectiveness has been shown in studies comparing it with placebo and reference antidepressants. Our own work supports the contention that LI 160, the best-documented St John's wort medication, is effective at a high dosage even in patients with severe depression. Since the new Berlin Aging Study revealed significant treatment deficiencies among elderly depressive patients, St John's wort extracts may be a useful alternative to benzodiazepines to avoid nontreatment of early depression. Because St John's wort preparations have better tolerability than tricyclic antidepressants, elderly people in particular, can benefit from their use.

Aged↗
PubMed2001

Interactions between herbal medicines and prescribed drugs: a systematic review.

Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified. The results indicate that St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens). In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences. Healthcare professionals should ask their patients about the use of herbal products and consider the possibility of herb-drug interactions.

Drug Interactions↗
PubMed2003

Mechanism of action of St John's wort in depression : what is known?

Extracts of Hypericum perforatum L. (St John's wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John's wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones. Although St John's wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John's wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, other in vitro binding assays carried out using St John's wort extract demonstrated significant affinity for adenosine, GABA(A), GABA(B) and glutamate receptors. In vivo St John's wort extract leads to a downregulation of beta-adrenergic receptors and an upregulation of serotonin 5-HT(2) receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John's wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John's wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John's wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John's wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids. This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John's wort and its active constituents with a large body of existing literature.

Animals↗
PubMed2005

Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase.

The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. John's wort), was recently identified as potent and direct inhibitor of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes. In this study, naturally occurring analogues of hyperforin, isolated from H. perforatum, as well as a series of synthetic derivatives obtained by chemical modification of hyperforin by acylation, alkylation or oxidation, were analysed for the inhibition of 5-LO. The efficacies of these compounds were evaluated in intact human polymorphonuclear leukocytes, but also the inhibitory effects on isolated recombinant human 5-LO were investigated. Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects.

Bridged Bicyclo Compounds↗
PubMed2004

The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication.

BACKGROUND: A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo. METHOD: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks. RESULTS: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed. CONCLUSIONS: The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Adult↗
PubMed2000

A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.

BACKGROUND: Depressive disorders are persistent, recurring illnesses that cause great suffering for patients and their families. PURPOSE: To evaluate the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and adolescents. DATA SOURCES: English-language and non-English-language literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts. STUDY SELECTION: Randomized trials evaluating newer antidepressants (such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort) that reported clinical outcomes were selected. DATA EXTRACTION: Two persons independently abstracted data that were then synthesized descriptively; some data were pooled by using a random-effects model. DATA SYNTHESIS: Of 315 eligible trials, most evaluated antidepressants in adults with major depression, were conducted among outpatients, and examined acute-phase treatment. Newer antidepressants were more effective than placebo for major depression (relative benefit, 1.6 [95% CI, 1.5 to 1.7]) and dysthymia (relative benefit, 1.7 [CI, 1.3 to 2.3]). They were effective among older adults and primary care patients. Efficacy did not differ among newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo for mild to moderate depression (risk ratio, 1.9 [CI, 1.2 to 2.8]), but publication bias may have inflated the estimate of benefit. Newer and older antidepressants did not differ for overall discontinuation rates, but side effect profiles varied significantly. Data were insufficient for determining the efficacy of newer antidepressants for subsyndromal depression, depression with coexisting medical or psychiatric illness, or depression in adolescents. CONCLUSIONS: Newer antidepressants are clearly effective in treating depressive disorders in diverse settings. Because of similar efficacy, both newer and older antidepressants should be considered when making treatment decisions. Better information is urgently needed on the efficacy of newer antidepressants in patients with nonmajor depression and in special populations, including adolescents.

Age Factors↗
PubMed1999

Pharmacodynamic properties of St. John's wort-A single blind neurophysiological study in healthy subjects comparing two commercial preparations.

In this clinical trial the effects on the central nervous system (CNS) of two commercially available extracts of St. John's wort (Texx 300 and Jarsin 300) were compared with those of placebo in a group of healthy young volunteers (n = 35) following a single blind study design. Measurements were carried out on the first day and after repetitive drug application (t.i.d.) over 3 weeks. In accordance to the known slow resorption of hypericum extracts maximum effects were observed for both preparations between 4 and 6 h after intake. Texx 300 produced alpha2 increases of up to 32% in comparison to placebo. Somewhat weaker increases were observed after Texx 300 within the beta frequencies (14% resp. 15%) and in alpha1 band (8%). Jarsin 300 produced less power increases within the alpha2 range. In addition beta increases were observed after Jarsin 300 following repetitive administration. Thus slight differences could be detected between the two preparations with respect to their maximum effects, but in general the profile of action was similar for both drugs becoming more clear after the repetitive dosing. However, the effects of Texx 300 occurred a little bit earlier possibly due to a better intestinal resorption. Concerning the auditory event related potentials both preparations tended to decrease the latency of the cognitive potential P 300 indicating an improvement of mental performance. The observed neurophysiological changes are in line with the proposed clinical efficacy of both plant extracts, especially with respect to the drug induced changes within the alpha1 and alpha2 frequency ranges known for being under serotonergic and dopaminergic control, respectively. These electrochemical features of brain activity are known to be of great importance during the course of action of antidepressive drugs. - In summary quantitative EEG proved to be able to discriminate between different extracts of St. John's wort with respect to time of effect and profile changes on neuronal communication structure.

Adult↗
PubMedDate not supplied

St. John's Wort extract: efficacy for menopausal symptoms of psychological origin.

Herbal remedies such as St. John's Wort preparations can be used successfully to relieve the psychological and vegetative symptoms of menopause. This drug-monitoring study investigated 12 weeks of treatment with St. John's Wort, one tablet three times daily (900 mg Hypericum, Kira), in 111 women from a general medical practice. The patients, who were between 43 and 65 years old, had climacteric symptoms characteristic of the pre- and postmenopausal state. Treatment outcome was evaluated by the Menopause Rating Scale, a self-designed questionnaire for assessing sexuality, and the Clinical Global Impression scale. The incidence and severity of typical psychological, psychosomatic, and vasomotor symptoms were recorded at baseline and after 5, 8, and 12 weeks of treatment. Substantial improvement in psychological and psychosomatic symptoms was observed. Climacteric complaints diminished or disappeared completely in the majority of women (76.4% by patient evaluation and 79.2% by physician evaluation). Of note, sexual well-being also improved after treatment with St. John's Wort extract.

Adult↗
PubMed2000

Modeling the recovery from depressive illness by an exponential model with mixed effects.

In clinical trials of antidepressant treatments, a depression rating score is usually measured at several points of time for each patient. We propose an approach to fit data from this type of clinical trial using an exponential mixed-effects model. Compared to previous proposals, this approach has the advantage that individual recovery curves are fitted rather than curves of means. Furthermore, no artificial fixing of model parameters is needed as in other approaches. The flexibility of the proposed model is shown for various situations. The approach is illustrated by an example from a placebo-controlled study for the treatment of depression with St. John's Wort (Hypericum perforatum).

Antidepressive Agents↗
PubMed2000

Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression.

Commercially available St. John's wort (Hypericum perforatum) extracts, preparations that are used in the treatment of depression, were examined for the potential to inhibit human cytochrome P450 (CYP) enzyme activities, specifically CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Crude extracts demonstrated inhibition of each of these five enzymes, with CYP2D6, CYP2C9, and CYP3A4 being more sensitive than CYP1A2 and CYP2C19. Extracts were fractionated by HPLC, and each of the fractions was tested for inhibition of these five CYPs to identify individual constituents with inhibitory activity. Several fractions were shown to possess inhibitory activity, including the fractions containing hyperforin (the putative active antidepressant constituent), I3,II8-biapigenin, and hypericin. Hyperforin and I3,II8-biapigenin were isolated from the extract, and inhibition constants for the five CYP activities were measured. In addition, three other constituents, hypericin, quercetin, and chlorogenic acid, were tested for inhibitory activity toward the CYP enzymes. The flavonoid compound I3,II8-biapigenin was shown to be a potent, competitive inhibitor of CYP3A4, CYP2C9, and CYP1A2 activities with K(i) values of 0.038, 0.32, and 0.95 microM, respectively. Hyperforin was a potent noncompetitive inhibitor of CYP2D6 activity (K(i) = 1.5 microM) and competitive inhibitor of CYP2C9 and CYP3A4 activities (K(i) = 1.8 and 0.48 microM, respectively). Hypericin also demonstrated potent inhibition of several CYP activities. These in vitro data indicate that St. John's wort preparations contain constituents that can potently inhibit the activities of major human drug-metabolizing enzymes and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo.

Anthracenes↗
PubMed2000

[Flavonoid and dianthranoid levels of the St.-John's-wort flowering tops].

Dried flowering tops of Hypericum perforatum L. (16 batches) and H. maculatum (3 batches) were studied according to the harvest period. The mean levels of the flavonoid and dianthranoid compounds were respectively: total flavonoids 3.20 and 3.92%, hyperoside 0.87 and 2. 12%, rutin 0.54 and 0.02%, isoquercitrin 0.48 and 0.75%; total dianthranoids 0.14 and 0.13%, hypericin 0.04 and 0.02%, pseudohypericin 0.08 and 0.11%. The flavonoid and dianthranoid levels were higher in young flowering tops of H. perforatum. 3 commercial batches were also examined for a comparative study. Pharmacopoeial specifications are proposed for a revision of the monograph "St.-John's-wort".

Anthracenes↗
PubMed2001

[The safety of herbal medicines in the psychiatric practice].

The use of alternative medicines is increasing world-wide and in Israel. These drugs, considered by the Ministry of Health as food supplements, are to be obtained at pharmacies and health stores and are being sold freely, without any professional advice. Many of the herbs are used by patients to treat psychiatric disorders. These herbs have a pharmacological activity, adverse effects and interactions with conventional drugs, which can produce changes in mood, cognition, and behavior. We present the most commonly used herbal drugs, and discuss their safety and efficacy in psychiatric practice. Hypericum--used as an antidepressant and as an antiviral medicine, was reported in 23 randomized clinical trials reviewed from the MEDLINE. It was found to be significantly more effective than placebo and had a similar level of effectiveness as standard antidepressants. Recent studies almost clearly prove that this herb, like most of the conventional antidepressants, can induce mania. Valerian--is used as an anti-anxiety drug, and reported to have sedative as well as antidepressant properties. In contrast to the significant improvement in sleep that was found with the use of valerian, compared to placebo, there are several reports on the valerian root toxicity. This includes nephrotoxicity, headaches, chest tightness, mydriasis, abdominal pain, and tremor of the hands and feet. Ginseng--another plant that is widely used as an aphrodisiac and a stimulant. It has been associated with the occurrence of vaginal bleeding, mastalgia, mental status changes and Stevens-Johnson syndrome after it's chronic administration. It has interactions with digoxin, phenelzine and warfarin. Ginkgo--in clinical trials the ginkgo extract has shown a significant improvement in symptoms such as memory loss, difficulties in concentration, fatigue, anxiety, and depressed mood. Long-term use has been associated with increased bleeding time and spontaneous hemorrhage. Ginkgo should be used cautiously in patients receiving aspirin, NSAIDs, anticoagulants or other platelet inhibitors. Health care professionals can no longer ignore the widespread use of alternative medicines and cannot continue with the "don't ask, don't tell" policy. Clinicians should ask the patients about their use of herbs in a non-judgmental way, and should document the patient's use of these drugs. Finally, we must be more aware of the side effects and the potential drug interactions of these herbs, and advise our patients to avoid long term use of these drugs due to lack of information regarding the safety of these medicines.

Ginkgo biloba↗
PubMed2002

[Metabolic effects and drug interactions provoked by certain vegetables: grapefruit, St. John's wort and garlic].

GRAPEFRUIT: Essentially consumed in the form of juices with its bitterness helping to quench thirst, grapefruit contains not only vitamin C but also many complex antioxidizers, licopene, lemonoids and naringine. It also contains large quantities of pectin. Grapefruit juice is a metabolic inhibitor of medicinal substances that constitute an exclusive target for the CYP 3A4 isozyme and glycoprotein P in the enterocytes. Above all, it affects the drugs with strong intestinal metabolic first pass effect, phenomenon provoking the reduction of their oral bioavailability. This metabolic inhibition is manifested by an increase in the serum levels, oral bioavailability and therapeutic activity of drugs metabolized by CYP 3A4, a characteristic that may indeed be interesting for some of them, but which should be avoided for others. ST. JOHN'S WORT: (Hypericum perforatum) Also known as "herbe à mille trous" or "herbe percée" or even "herbe de Saint-Jean" in France, St. John's wort is used in several therapeutic fields: neuropsychiatry, dermatology (oleate or lipid extract) and in rheumatology. In herbal remedies and homeopathy, the flower heads are often prescribed as antidepressor in the treatment of mild to moderate depression. It also contains photosensitizing substances, which, at high dose, or during chronic use, may provoke intense dermatitis or photosensitivity. The potential occurrence of side effects with its use has led the European Agency for drug assessment and the French Medicines Agency to decree that all magistral preparations containing St. John's wort must be labeled: "Warning, risk of drug interactions". GARLIC: (Allium salivum) Originating from Asia, widespread and cultivated in Europe in kitchen gardens, garlic is used by herbalists for its diuretic, antiseptic, stimulating and sudorific properties.

Beverages↗
PubMedDate not supplied

Determination of St. John's wort components in dietary supplements and functional foods by liquid chromatography.

St. John's wort (Hypericum perforatum L.) preparations, a top-selling botanical dietary supplement used primarily as an antidepressant, has recently been used as an ingredient in some food products sold as functional foods. A rapid extraction technique followed by a liquid chromatographic (LC) method was developed to determine 4 characteristic bioactive compounds (pseudohypericin, hypericin, hyperforin, and adhyperforin) from St. John's wort in dietary supplements and functional foods to which it was added. Solid samples, including dried leaf/flower mixture, dietary supplement capsules, tea bags, puff and snack bar, were extracted with methanol by sonication. Noncarbonated, fruit-flavored drinks were centrifuged and mixed with methanol. Compounds were then determined by isocratic, reversed-phase LC with UV detection at 2 wavelengths and further identified or confirmed by photodiode array spectra and LC/mass spectrometry. Within-laboratory method variations (% RSD) were satisfactory. Very low amounts, if any, of the 4 components were found in drink and puff samples, and none was found in the snack bar. The methods developed provide a useful means for the determination of St. John's wort components in dietary supplements and functional foods.

Algorithms↗
PubMed2002

Surveys of microfungi in a former industrial area in Duisburg-Nord.

One hundred and forty microfungi (Ascomycetes and Deuteromycetes) were collected in the "Landschaftspark Duisburg-Nord" located in North Rhine-Westphalia. New hosts for rarely found fungi are recorded for the first time. New for Germany are Massaria inquinans (Tode) De Not. and Nitschkia grevillei (Rhem) Nannf. on Acer pseudoplatanus L., Pirottaea nigrostriata Graddon on Artemisia vulgaris L., Ceratopycnis clematidis Höhn. on Clematis vitalba L., Dasyscyphus aff. humuli (W. Phillips) Dennis on Humulus lupulus L. and Leptosphaeria derasa (Berk. & Br.) Auersw. on Senecio inaequidens DC. New for North Rhine-Westphalia are Chaetosphaerella phaeostroma (Durieu & Mont.) E. Müller & Booth and Phomopsis platanoides (Cooke) Died. on Acer pseudoplatanus L., Microsphaeropsis pseudaspera Sutton, Mycosphaerella osborniae D. Hawksw. & Sivan. and Phomopsis oblita Sacc. on Artemisia vulgaris L., Leptosphaeria acuta (Fr.) P. Karst. and Leptosphaeria doliolum (Pers.) Ces. & De Not. on Bryonia dioica Jacq., Ophiobolus erythrosporus (Riess) G. Winter and Pleospora herbarum (Pers.) Rabenh. ex Ces. & De Not. on Dipsacus sylvestris (Huds), Keissleriella ocellata (Niessl) Bose on Hypericum perforatum L., Dactylaria aff. graminicola on Lolium perenne L., Siroplacodium aff. atrum on Oenothera beinnis L., Diatrypella favacea (Fr.) Sacc. on Prunus spec., Hapalosphaeria deformans (Syd.) Syd. and Microdiscula rubicola (Bres.) Höhn. on Rubus fructicosus agg. L., Cryptodiaporthe salicina (Pers.) Wehm. on Salix alba L. and Pleurophoma pleurospora (Sacc.) Höhn. on Salix caprea L.

Acer↗
PubMed2002

Role of antioxidants in chronic fatigue syndrome in mice.

The present study was carried out using mice model of chronic fatigue syndrome (CFS) in which mice were forced to swim everyday for 7 days for a 6 min session. There was a significant increase in despair behavior (immobility period) in saline treated mice on successive days. Treatment with potent antioxidants carvedilol (5 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) produced a significant reduction in immobility period. Similar results were observed with herbal products St. John's Wort (Hypericum perforatum L) (10 mg/kg, p.o.) and GS-02 (20 mg/kg, p.o.). Fluoxetine, a selective serotonin reuptake inhibitor produced a significant effect only on first and second day of its treatment. Biochemical analysis revealed that chronic swim test significantly increased lipid peroxidation and catalase levels in whole brains of mice. There was a decrease in the levels of super oxide dismutase (SOD) and glutathione reductase (GSH) in the brain. Administration of carvedilol, melatonin, GS-02 and St. John's Wort restored the levels of lipid peroxidation and glutathione. The enzymes SOD and catalase were also restored. Fluoxetine affected the biochemical variables not to the same extent as other treatments. The findings of the present study suggest that oxidative stress might play a significant role in the pathophysiology of CFS. Thus antioxidants and herbal products like St. Johns wort and GS-02 could be useful in the treatment of CFS.

Animals↗
PubMed2003

St. John's wort extracts and some of their constituents potently inhibit ultimate carcinogen formation from benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1.

Commercially available St. John's wort (Hypericum perforatum) preparations and some of their main constituents (hypericin, pseudohypericin, hyperforin, rutin, and quercetin) were examined for their potential to inhibit carcinogen activation by human cytochrome P450 1A1 (CYP1A1). We used a reconstituted system consisting of purified human CYP1A1, purified human NADPH-cytochrome P450 reductase, and dilaurylphosphatidylcholine as lipid component. St. John's wort extracts potently inhibited CYP1A1-catalyzed (+/-)-trans-7,8-dihydro-7,8-dihydroxy-benzo(a)pyrene (7,8-diol-B[a]P) epoxidation, the terminal reaction leading to the ultimate carcinogenic product (+/-)-B[a]P-r-7,t-8-dihydrodiol-t-9,10-epoxide (diolepoxide 2). All constituents, except rutin, were shown to possess strong inhibitory potencies toward diolepoxide 2 formation from 7,8-diol-B[a]P, with IC(50) values of 0.5 microM (hypericin), 1.2 microM (hyperforin), 1.5 microM (quercetin), and 8 microM (pseudohypericin), respectively. Preincubation experiments revealed that their action was not mechanism based. Inhibition kinetics studies showed the anthrodianthrone compound hypericin to be a noncompetitive inhibitor, with a K(i) value of 0.6 microM, and the phloroglucinol hyperforin to be a competitive inhibitor, with a K(i) value of 1.1 microM. When the effects on NADPH-P450 reductase activity were investigated, all constituents of St. John's wort studied turned out to be rather ineffective inhibitors; quercetin was the only exception, with an IC(50) value of approximately 20 microM. These in vitro data indicate that St. John's wort extracts and some of their constituents potently inhibit the major human procarcinogen-activating enzyme CYP1A1.

Animals↗