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PubMed2000

Effect of topical application of Hypericum perforatum extract (St. John's wort) on skin sensitivity to solar simulated radiation.

St. John's wort (Hypericum perforatum) is a tradional folk remedy that is used for the topical treatment of superficial wounds, scars and burns. A characteristic metabolite of St. John's wort is the photodynamic active plant pigment hypericin. It is known that hypericin may cause a severe photodermatitis called hypericism when higher amounts of St. John's wort are ingested orally. To date, no reports on the photosensitizing capacity of topical application of St. John's wort are available. Here, we investigated the effects of Hypericum oil (hypericin 110 microg/mL) and Hypericum ointment (hypericin 30 microg/mL) on skin sensitivity to solar simulated radiation. Sixteen volunteers of the skin types II and III were tested on their volar forearms with solar simulated radiation for photosensitizing effects of Hypericum oil (n=8) and Hypericum ointment (n=8). The minimal erythema dose (MED) was determined by visual assessment, and skin erythema was evaluated photometrically. With the visual erythema score, no change of the MED could be detected after application of either Hypericum oil or Hypericum ointment (P>0.05). With the more sensitive photometric measurement, an increase of the erythema-index after treatment with the Hypericum oil could be detected (P< or =0.01). The results do not provide evidence for a severe phototoxic potential of Hypericum oil and Hypericum ointment, detectable by the clinically relevant visual erythema score. However, the trend towards increased photosensitivity detected with the more sensitive photometric measurement could become relevant in fair-skinned individuals, in diseased skin or after extended solar irradiation.

Administration, Cutaneous↗
PubMed1997

The effect of hypericum extract on cardiac conduction as seen in the electrocardiogram compared to that of imipramine.

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.

Adult↗
PubMed2000

Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells.

St John's wort (Hypericum perforatum) is a traditional herbal medicine that is used for the topical treatment of superficial wounds, burns and dermatitis. The characteristic metabolites of St John's wort are the photodynamic active plant pigment hypericin and the phloroglucin-derivative hyperforin. To date, no studies on immunomodulatory properties of topical preparations of St John's wort have been performed. Here, we investigated the alloantigen presenting function of human epidermal cells (EC) exposed to Hypericum ointment in vivo in a mixed EC lymphocyte reaction (MECLR). The effect of Hypericum ointment was compared with the immunosuppressive effect of solar-simulated radiation (SSR). Subsequently, we tested purified hyperforin in vivo and in vitro in a MECLR to evaluate its possible contribution to the effect of the Hypericum ointment. Furthermore, we assessed the effect of hyperforin on the proliferation of peripheral blood mononuclear cells (PBMC) in vitro. Compared with untreated skin, treatment with Hypericum ointment resulted in a significant suppression of the MECLR (P </= 0.001) that was similar to the effect of SSR. The combination of Hypericum ointment plus SSR was not significantly different from either treatment alone. EC isolated from skin treated with the hyperforin containing ointment also showed a reduced capacity to stimulate the proliferation of allogeneic T cells (P </= 0.001). Similarly, in vitro incubation of EC with hyperforin suppressed the proliferation of alloreactive T cells (P </= 0.001). Furthermore, hyperforin inhibited the proliferation of PBMC in a dose-dependent manner, without displaying pronounced toxic effects as determined by Trypan blue staining. The results demonstrate an inhibitory effect of Hypericum extract and of its metabolite hyperforin on the MECLR and on the proliferation of T lymphocytes that may provide a rationale for the traditional treatment of inflammatory skin disorders with Hypericum extracts.

Adjuvants, Immunologic↗
PubMedDate not supplied

Extracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki Forest virus system.

Extracts, fractions and constituents of Hypericum perforatum were studied for in vitro receptor binding with various ligands to recombinant CNS receptors expressed with the Semliki Forest virus expression system. For this purpose we have prepared membranes of CHO cells with high density of several opioid, serotonin, estrogen, histamine, GABAA, neurokinin and metabotropic glutamate receptors, respectively. A lipophilic Hypericum fraction revealed relatively potent inhibition to the binding of the mu-, delta- and kappa-opioid and the 5-HT6 and 5-HT7 receptors. Moreover, Hypericum constituents such as the naphthodianthrones, hypericin and pseudohypericin, and the phloroglucinole hyperforin inhibited both binding to the opioid and serotonin receptors in the lower micromolar range. Estrogen binding was 50% inhibited by the biflavonoid I3,II8-biapigenin at micromolar concentration. The lipophilic Hypericum fraction provided a less potent inhibition of the neurokinin-1 receptor binding compared to the opioid and serotonin receptors. A total ethanolic Hypericum extract potently inhibited GABAA binding at approximately 3 micrograms/ml. This inhibition is however not specific to Hypericum, since extracts of plants like Valeriana officinalis and Passiflora incarnata showed similar inhibitions. Binding to neither histamine nor metabotropic glutamate receptors was affected by Hypericum extracts. These results support the hypothesis that several active constituents of Hypericum might in a synergistic way contribute to its antidepressant effect in the central nervous system.

Animals↗
PubMed2001

St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.

RATIONALE: St. John's wort (Hypericum perforatum) has recently gained popularity as an alternative treatment for mild to moderate depression. Given the current widespread use of this herbal remedy, it is important for medical professionals to understand the potential pharmacological pathways through which Hypericum may exert an antidepressant effect. OBJECTIVES: (1) To review the current pharmacological, toxicological, and clinical literature available on Hypericum, and (2) to provide a synthesis of this information into a form that may be easily used by health care providers. METHOD: A comprehensive review of the recent scientific literature (January 1990-March 2000) was performed using the following electronic databases and reference publications: MEDLINE, The Cochrane Library, HealthSTAR, Current Contents (all editions), European Scientific Cooperative on Phytotherapy monographs, German Commission E monographs, and the Physicians' Desk Reference for Herbal Medicines, 1st edition. RESULTS: One hundred and seven (107) publications in the English language and three publications in German were included in the review. Collectively, the data suggest that therapeutic preparations of Hypericum extract appear to exert potentially significant pharmacological activity within several neurochemical systems believed to be implicated in the pathophysiology of depression. However, little information exists regarding the safety of Hypericum, including potential herb-drug interactions. CONCLUSIONS: Additional research on the pharmacological and biochemical activity of Hypericum and its several bioactive constituents is necessary to further elucidate the mode(s) of antidepressant action. Given what is currently known and unknown about the biological properties of Hypericum, those who choose to use this herb should be closely monitored by a physician.

Animals↗
PubMed2001

Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice.

Depression, among other non-cognitive symptoms, is common in patients with dementia. The effect of Hypericum perforatum (St. John's Wort) extract, with well-documented antidepressant activity, was tested on memory retrieval 24 h after training on a one-trial passive avoidance task in mice. Acute administration of Hypericum extract (4.0, 8.0, 12.0, and 25.0 mg/kg i.p.) before retrieval testing increased the step-down latency during the test session. The same doses of Hypericum extract, on the other hand, failed to reverse scopolamine-induced amnesia of a two-trial passive avoidance task. The involvement of serotonergic, adrenergic, and dopaminergic mechanisms in the facilitatory effect of Hypericum extract on retrieval memory was investigated. Pretreatment of the animals with serotonergic 5-HT1A receptor antagonist (-)-pindolol (0.3, 1.0, and 3.0 mg/kg), serotonergic 5-HT2A receptor blocker spiperone (0.01, 0.03, and 0.1 mg/kg), alpha adrenoceptor antagonist phentolamine (1, 5, and 10 mg/kg), beta receptor antagonist propranolol (5, 7.5, and 10 mg/kg), dopaminergic D1 receptor antagonist SCH 23390 (0.01, 0.05, and 0.1 mg/kg), and dopaminergic D2 receptor antagonist sulpiride (5, 7.5, and 10 mg/kg) revealed the involvement of adrenergic and serotonergic 5-HT1A receptors in the facilitatory effect of Hypericum extract on retrieval memory. It is concluded that Hypericum extract may be a better alternative for treatment of depression commonly associated with dementia than other antidepressants known to have anticholinergic side effects causing delirium, sedation and even exacerbating already existing impaired cognition. In dementias of old age, Hypericum perforatum would, therefore, serve as one medication targeting both depression and amnesia with lower potential side effects.

Amnesia↗
PubMed1999

Comparison of hypericum extracts with imipramine and fluoxetine in animal models of depression and alcoholism.

Clinical evidence suggests that hypericum extracts (Hypericum perforatum L., St. John's wort) have antidepressive properties and may offer an interesting alternative for the treatment of mood disorders. In addition, hypericum extracts, as well as standard antidepressants such as the tricyclic, impramine, and the selective serotonin reuptake inhibitor, fluoxetine, have been reported to be of therapeutic benefit in the treatment of alcoholism, as these compounds may reduce alcohol craving and/or intake in particular subgroups of patients. It was the aim of the present study to compare the effects of hypericum extracts with those of imipramine and fluoxetine in the rat forced swimming test (RFST), a model of depression, as well as in cAA rats, a genetic model of alcoholism. In the RFST, triple i.p. administration of imipramine (3-30 mg/kg) and fluoxetine (3-30 mg/kg) induced a dose-dependent reduction in immobility: the minimal effective dose (MED) being 30 and 10 mg/kg, and the maximal effect being 50% and 57% immobility reduction, for imipramine and fluoxetine, respectively. In this test, the hypericum extracts Ze 117 (Remotiv) and LI 160 (Jarsin) also induced a statistically significant reduction of immobility when administered under the same application schedule (5-40 mg/kg, i.p., triple application). In the case of the hypericum extracts the dose-response relationship was inverted U-shaped with a MED value of 20 mg/kg and a maximal effect of 41% and 32% immobility reduction, for Ze 117 and LI 160, respectively. Interestingly, the anti-immobility effects tended to be more pronounced after subacute (1 week, B.I.D.) treatment with 10 mg/kg of imipramine, fluoxetine, or Ze 117, as compared with acute treatment. This phenomenon is in accordance with clinical experience and suggests that repeated treatment is required for full development of antidepressive effects. In the alcohol-preferring cAA rats, acute i.p. administration of imipramine (3-30 mg/kg), fluoxetine (1-10 mg/kg) and Ze 117 (10-40 mg/kg) dose-dependently reduced alcohol intake in a 12-h limited access two-bottle [ethanol 10% (v/v) versus water] choice procedure: with MED values of 30, 5 and 20 mg/kg, respectively. The anti-alcohol effects of fluoxetine and Ze 1-17 appeared to be specific, as reductions in alcohol intake coincided with reductions in alcohol preference. The present study suggests that hypericum extracts have antidepressant-like properties which resemble those of clinically established antidepressants, and that Remotiv may be an interesting adjunct for the treatment of alcoholism.

Alcoholism↗
PubMed2000

Effect of the Hypericum perforatum extract on serotonin turnover in the mouse brain.

St. John's Wort, a traditional herbal medicine obtained from the extract of Hypericum perforatum, has been used in the treatment of mild depression. Its mechanism of action remains to be established. The present study confirmed that Hypericum extract exhibited very weak inhibitory activities towards MAO. Mouse brain MAO activities was unchanged following either acute or chronic treatment with Hypericum extract. 5-HIAA levels were found to be significantly increased in the cerebral cortex, hypothalamus, hippocampus and caudate 3 h after treatment with the Hypericum extract at a dose as low as 10 mg/Kg. An increase of 5-HT levels was also observed in hypothalamus and hippocampus. The increase of brain 5-HIAA was not further enhanced following chronic administration of the herb. The Hypericum extract significantly reduced the plasma tryptophan levels, the precursor of 5-HT. The action of Hypericum extract is consistent with the notion that serotonergic system is involved. The effect of Hypericum extract on the brain 5-HIAA and 5-FIT levels appeared to be quite different from the effect of classical 5-HT re-uptake blockers.

Animals↗
PubMed2000

Effect of acute administration of hypericum perforatum-CO2 extract on dopamine and serotonin release in the rat central nervous system.

The hydromethanolic extract of Hypericum perforatum has been shown to be an effective antidepressant, although its mechanism of action is still unclear. In this study, in vivo microdialysis was used to investigate the effects of Hypericum perforatum-CO2 extract on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) release in various areas of brain. Administration of Hypericum perforatum extract (1 mg/kg, p.o.) caused a slight, but significant increase of DA outflow both in the nucleus accumbens and the striatum. The maximal increase of DA efflux (+19.22+/-1.93%, relative to the control group) in the nucleus accumbens occurred 100 min after administration of Hypericum perforatum. In the striatum, the extract maximally enhanced DA outflow (+24.83+/-7.49 %, relative to the control group) 80 min after administration. Extraneuronal DOPAC levels were not significantly affected by Hypericum perforatum treatment. Moreover, Hypericum perforatum (1 mg/kg, p.o.) did not produce any significant effect on either 5-HT or 5-HIAA efflux in the ventral hippocampus. This study shows for the first time that Hypericum perforatum extract is capable of increasing in vivo DA release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum.

Hypericum perforatum is considered an effective alternative to the synthetic antidepressants in the treatment of mild-to-moderate depression. Recently, we showed that the effects on neurotransmitter contents in different brain regions of laboratory animals are more evident after administration of hypericum extracts containing a higher concentration of flavonoids, thus suggesting that these compounds are important in the antidepressant action of hypericum perforatum. We studied the effects of Ph-50, a hypericum extract standardized to flavonoids (50%) and containing 0.3% hypericin and 4.5% hyperforin on brain serotonin content, norepinephrine and dopamine by a high-performance liquid chromatography method in discrete brain areas (cortex, diencephalon and brainstem) in male Sprague-Dawley rats. Moreover, we evaluated the effects of Ph-50 alone or in association with sulpiride (a dopamine receptor antagonist), metergoline (a serotonin receptor antagonist) and 6-hydroxydopamine (6-OH-DA, destroying norepinephrine-containing neurons) using a forced-swimming test in the rat. Hypericum extract (Ph-50; 250-500 mg/kg) with acute oral administration enhanced serotonin, norepinephrine and dopamine content in the brain and reduced the immobility time of rats in the forced-swimming test. Sulpiride, metergoline and 6-OH-DA significantly increased the period of immobility in the forced-swimming test for the rats receiving hypericum extract (Ph-50). The results indicate that the neurotransmitters studied could be involved in the anti-immobility effects of hypericum, and suggest that its antidepressant action is probably mediated by serotonergic, noradrenergic and dopaminergic system activation.

Animals↗
PubMed1999

Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.

OBJECTIVES: To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression. DESIGN: Randomised, double blind, multicentre, parallel group trial for 8 weeks. SETTING: Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony. PARTICIPANTS: 263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1. INTERVENTIONS: 1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily. MAIN OUTCOME MEASURES: Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile. RESULTS: Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively). CONCLUSIONS: At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

Adult↗
PubMed2000

Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.

BACKGROUND: Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVE: This study compared hypericum and the SSRI sertraline in the treatment of depression. METHODS: In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks. RESULTS: The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size. CONCLUSION: The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.

Adolescent↗
PubMed1997

Effects of long-term administration of hypericum extracts on the affinity and density of the central serotonergic 5-HT1 A and 5-HT2 A receptors.

Extracts of St. John's wort, Hypericum perforatum L. (Hypericaceae), are used as a phytotherapeutic antidepressant. A number of clinical studies demonstrate that their antidepressive potency is comparable to tricyclic antidepressants (TCA). Although the therapeutic effect of hypericum extracts is well documented, very little is known about the molecular mode of action. As the improvement of the depressive symptoms with both TCA and hypericum extracts only occurs significantly after a lag phase of 10 to 14 days, it is assumed that the medication causes long-term adaptations within the central nervous system. In this context, serotonergic (5-HT) receptors are of special interest. Therefore, we investigated possible alterations in affinity and density of 5-HT1 A and 5-HT2 A receptors caused by long-term treatment of rats with St. John's wort. The brain without cerebellum and brain stem of rats, treated daily for 26 weeks with a commercially available hypericum extract (2700 mg/kg LI 160) were used for membrane preparations. Affinity (KD) and amount (Bmax) of serotonergic receptors were determined by employing receptor binding assays using 3 H-8-OH-DPAT and 3H-Ketanserin as selective radioligands for the 5-HT1 A and the 5-HT2 A receptors, respectively. We found that in hypericum-treated rats the number of both 5-HT1 A and 5-HT2 A receptors were significantly increased by 50% compared to controls, whereas the affinity of both serotonergic receptors remained unaltered. The data suggest an upregulation of 5-HT1 A and 5-HT2 A receptors due to prolonged administration of hypericum extracts. These results are consistent with a modification of the expression levels of serotonergic receptors caused by synthetic antidepressants.

Animals↗
PubMed2000

An open-label trial of St. John's Wort (Hypericum perforatum) in obsessive-compulsive disorder.

BACKGROUND: Recent interest in and evidence for the efficacy of St. John's wort (Hypericum perforatum) for the treatment of mild-to-moderate depression has led to speculation about its efficacy in other disorders. Hypericum's mechanism of action is postulated to be via inhibition of the synaptosomal uptake of serotonin. As such, there is a suggestion that Hypericum may be effective for obsessive-compulsive disorder (OCD). METHOD: Twelve subjects were evaluated with a primary DSM-IV diagnosis of OCD of at least 12 months' duration. Treatment lasted for 12 weeks, with a fixed dose of 450 mg of 0.3% hypericin (a psychoactive compound in Hypericum) twice daily (extended-release formulation). Weekly evaluations were conducted with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Patient Global Impressions of Improvement Scale, and the Clinical Global Impressions of Improvement scale (CGI) and monthly evaluation with the Hamilton Rating Scale for Depression. RESULTS: A significant change from baseline to endpoint was found, with a mean Y-BOCS change of 7.4 points (p = .001). Significant change occurred at 1 week (p = .020) and continued to increase throughout the trial. At endpoint, 5 (42%) of 12 were rated "much" or "very much improved" on the clinician-rated CGI, 6 (50%) were "minimally improved," and 1 (8%) had "no change." The most common side effects reported were diarrhea (N = 3) and restless sleep (N = 2). CONCLUSION: Significant improvement was found with Hypericum, with a drop-in Y-BOCS score similar to that found in clinical trials. The fact that a significant change was found as early as 1 week into treatment suggests a possible initial placebo response, although improvement grew larger over time. Results warrant a placebo-controlled study of Hypericum in OCD.

Adult↗
PubMed1997

Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum.

Flower extracts of Hypericum perforatum, Hypericum hirsutum, Hypericum patulum and Hypericum olympicum efficiently inhibited binding of [3H]flumazenil to rat brain benzodiazepine binding sites of the GABAA-receptor in vitro with IC50 values of 6.83, 6.97, 13.2 and 6.14 micrograms/ml, respectively. Single constituents of the extracts like hypericin, the flavones quercetin and luteolin, the glycosylated flavonoides rutin, hyperoside and quercitrin and the biflavone 13, II8-biapigenin did not inhibit binding up to concentrations of 1 microM. In contrast, amentoflavone revealed an IC50 = 14.9 +/- 1.9 nM on benzodiazepine binding in vitro. Comparative HPLC analyses of hypericin and amentoflavone in extracts of different Hypericum species revealed a possible correlation between the amentoflavone concentration and the inhibition of flumazenil binding. For hypericin no such correlation was observed. Our experimental data demonstrate that amentoflavone, in contrast to hypericin, presents a very active compound with regard to the inhibition of [3H]-flumazenil binding in vitro and thus might be involved in the antidepressant effects of Hypericum perforatum extracts.

Animals↗
PubMed1999

The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.).

Hypericum (St John's Wort) is a plant that has been used for centuries as a medicinal herb. Pre-clinical animals studies suggest that hypericum is effective in three major biochemical systems relevant for antidepressant activity, namely the inhibition of the synaptic re-uptake system for serotonin (5-HT), noradrenaline (NA) and dopamine (DA). It is the only antidepressant capable of inhibiting the re-uptake of 5-HT, NA and DA with similar potencies. The potencies for monoamine re-inhibition and chronic changes in receptors are also consistent with changes seen with known antidepressants. Behavioral studies suggest that hypericum is active in pre-clinical animal models of depression with comparable effects to known antidepressants. Supporting the pre-clinical pharmacology and efficacy, many clinical studies have shown that hypericum has superior efficacy compared to placebo and comparable efficacy to standard antidepressants in the treatment of mild-to-moderate depression. The advantage of hypericum over other antidepressants may result from its favorable side-effect profile. Although pre-clinical and short-term clinical studies demonstrate antidepressant activity, the lack of long-term use and efficacy, and the heterogeneity of patients, interventions, extract preparations from previous clinical studies suggests that more careful and controlled studies are needed to determine the long-term efficacy of hypericum in mild-to-moderate depression.

Animals↗
PubMed1999

Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes.

Extracts of Hypericum perforatum, commonly known as St. John's wort, are frequently used in Germany and other European countries to treat mild to moderately severe depression, but the mechanism of antidepressant activity of Hypericum is not understood. Because known mechanisms of antidepressant activity include inhibition of serotonin and/or norepinephrine uptake, we investigated the effects of standardized extracts of Hypericum LI 160 on the transport of these monoamine neurotransmitters into astrocytes, cells which surround synaptic terminals and regulate neurotransmission by means of their uptake systems. We found that LI 160 inhibited both serotonin and norepinephrine uptake in a dose-dependent manner. The two monoamine transport systems were affected differently by LI 160: for serotonin, the main effect was a 50% decrease in the rate of maximal transport, whereas for norepinephrine, the main effect was a 4.5 fold reduction in the apparent affinity of norepinephrine for its uptake sites. Upon removal of LI 160, uptake was restored, thereby indicating that the inhibition was not due to a toxic effect of Hypericum on the cells. These findings suggest that the ability of LI 160 to inhibit serotonin and norepinephrine uptake may underlie the antidepressant activity of this Hypericum extract.

Animals↗
PubMed1999

Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum).

OBJECTIVE: Extracts of St John's wort (Hypericum perforatum) are widely used in the treatment of depression, often as an over-the-counter drug. In contrast to its frequent use, knowledge about the pharmacokinetics of ingredients and drug interactions of St John's wort is poor. We studied the interaction between hypericum extract LI160 and digoxin. METHODS: The pharmacokinetics of digoxin were investigated in a single-blind, placebo-controlled parallel study. After the achievement of steady state for digoxin on day 5, healthy volunteers received digoxin (0.25 mg/d) either with placebo (n = 12) or with 900 mg/d LI160 (n = 13) for another 10 days. Digoxin concentration profiles on day 5 were compared with day 6 (single-dose interaction) and day 15 (tenth day of co-medication). RESULTS: There was a highly significant combined-day-and-group effect for digoxin area under the plasma concentration-time curve [AUC(0-24); P = .0001], peak concentration in plasma (Cmax; P = .0001), and plasma drug concentration at the end of a dosing interval (P = .0003) by two-way ANOVA. No statistically significant change was observed after the first dose of hypericum extract [AUC(0-24) at day 6 of 18.1+/-2.9 microg x h/L and 17.7+/-3.0 microg x h/L, mean +/- SD for placebo and hypericum group, respectively]. However, 10 days of treatment with hypericum extract resulted in a decrease of digoxin AUC(0-24) by 25% (day 15, 17.2+/-4.0 microg x h/L and 12.9+/-2.3 microg x h/L; P = .0035). Furthermore, comparison with the parallel placebo group after multiple dosing showed a reduction in trough concentrations and Cmax of 33% (P = .0023) and 26% (P = .0095), respectively. The effect became increasingly pronounced until the tenth day of co-medication. CONCLUSION: As with grapefruit juice, a food product, physicians should also be aware of potential drug-herb interactions. The interaction of St John's wort extract with digoxin kinetics was time dependent. The mechanism involved may be induction of the P-glycoprotein drug transporter.

Adult↗