Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypericum perforatum L. Hypericaceae (St. John's wort), has been used since the time of ancient Greece for its many medicinal properties. Modern usage is still quite diverse and includes wound healing, kidney and lung ailments, insomnia and depression. This plant has been known to contain a red pigment, hypericin, and similar compounds, which have been assumed to be the primary active constituent(s) in this plant genus. A crude Hypericum extract was tested in a battery of 39 in vitro receptor assays, and two enzyme assays. A sample of pure hypericin was also tested. Hypericin had affinity only for NMDA receptors while the crude extract had significant receptor affinity for adenosine (nonspecific), GABAA, GABAB, benzodiazepine, inositol triphosphate, and monoamine oxidase (MAO) A and B. With the exception of GABAA and GABAB, the concentrations of Hypericum exact required for these in vitro activities are unlikely to be attained after oral administration in whole animals or humans. These data are consistent with recent pharmacologic evidence suggesting that other constituents of this plant may be of greater importance for the reported psychotherapeutic activity. Alternative pharmacologic mechanisms for Hypericum's antidepressant activity are critically reviewed and the possible importance of GABA receptor binding in the pharmacology of Hypericum is highlighted. Some of these results have been previously reported.
 ...
PMID:In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. 934 70

There is increasing interest in and use of the herbal preparation St. John's wort. Hypericin, the major active ingredient, has many psychoactive properties. The agent is sold in the US as a nutritional supplement and is recommended for numerous conditions, including depression, anxiety, insomnia, and inflammation. We report a series of five cases of clinically diagnosed central serotonergic syndrome among elderly patients who combined prescription antidepressants with St. John's wort. Older adults are large consumers of both over-the-counter and prescription medications. They are particularly vulnerable to interactions between medications and products sold as nutritional or herbal supplements. St. John's wort requires further evaluation due to potential for drug interactions with central nervous system agents and for more definitive therapeutic indications.
 ...
PMID:St. John's wort and antidepressant drug interactions in the elderly. 1044 48

The plant Hypericum perforatum is used in folk medicine to treat several diseases and research attention has been recently focused on its antidepressant action. Hypericin and flavonoids are the most important constituents of the plant, but the exact role of these compounds in the effects of hypericum on mood disorders is not well known. We have investigated the contribution of these compounds to the antidepressant effects of hypericum. The effects of acute administration of hypericum extracts on levels of 5-hydroxytryptamine (5-HT), tryptophan, 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline and dopamine in the cortex, diencephalon and brainstem was evaluated. The levels of these neurotransmitters were measured 1 h and 24 h after administration of two different extracts, one containing 0.3% hypericin and 6% flavonoids (Li 160; 25-500 mgkg(-1)), the other containing 0.3% hypericin and 50% flavonoids (Ph-50; 25-500 mgkg(-1)). Results from experiments performed on 5-HT turnover were compared with the effects of fluoxetine (10-80 mgkg(-1)). Li 160, Ph-50 and fluoxetine induced a significant increase in the 5-HT content of the cortex. In the diencephalon Ph-50, but not Li 160 or fluoxetine, elicited an increase in 5-HT and 5-HIAA levels. In the brainstem Ph-50 and fluoxetine caused an increase in 5-HT content; Li 160 did not change neurotransmitter content. Both Li 160 and Ph-50 caused increases of noradrenaline and dopamine in the diencephalon. In the brainstem only Ph-50 induced an increase in noradrenaline content. Our data confirm that acute administration of hypericum extracts modifies the levels of neurotransmitters involved in the pathophysiology of mood disorders. When the extracts contain a higher concentration of flavonoids the effects are more widespread and involve brain regions such as diencephalon and brainstem that are implicated in depression.
 ...
PMID:Effects of Hypericum perforatum on levels of 5-hydroxytryptamine, noradrenaline and dopamine in the cortex, diencephalon and brainstem of the rat. 1045 50

Hypericum perforatum L. (St. John's Wort) is a widely distributed herbaceous perennial plant which has been well known as a medicinal plant since antiquity. In recent years, H. perforatum has received increasing attention for the treatment of depression and other neuralgic disorders. The main constituents of H. perforatum extract include flavonoids, naphthodianthrones, phloroglucinols, essential oils and xanthones. The present work reports the analysis of naphthodianthrones and phloroglucinols in H. perforatum extracts by means of high performance liquid chromatography (HPLC) coupled simultaneously to a diode array detector (DAD) and electrospray mass spectrometry (ESI-MS). Hypericin, pseudohypericin, hyperforin and adhyperforin were separated and identified on the base of their on-line UV and mass spectra. Quantitative analysis of hypericin derivatives in different extracts of H. perforatum using DAD and MS detectors was performed. In addition, direct infusion ESI-MS of H. perforatum extracts was applied to obtain rapid mass fingerprints of constituents present in the sample.
 ...
PMID:High performance liquid chromatography/electrospray mass spectrometry of Hypericum perforatum extracts. 1062 36

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.
 ...
PMID:Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression. 1087 Dec 99

Interactions between neurotransmitter receptors involved in the pathophysiology of depression, anxiety and ethanol consumption and two extracts (hydromethanolic and lipophilic extracts obtained with hypercritical CO2) from Hypericum Perforatum L or St. John's wort (SJW) and three constituents (hyperforin, hypericin and biapigenin) were evaluated by in vitro binding assays. The two extracts, tested at 10 microg/ml, did not inhibit ligand binding at the following receptors: serotonin 5-HT6 and 5-HT7, benzodiazepine, sigma and neuropeptide Y (NPY) Y1 and Y2 receptors. The hydromethanolic extract, but not the lipophilic extract, interacted with GABA(A) receptors (IC50 5.5 microg/ml), while both interacted with the dopamine (DA) transporters, albeit with high IC50 values (24.5 and 12.9 microg/ml, respectively). Biapigenin (1 microg/ml, 2 microM) inhibited ligand binding at benzodiazepine receptors only (IC50: 2 microM). Hyperforin (1 microg/ml, 2 microM) only inhibited [3H]WIN-35,428 binding to DA transporters, although the IC50 (5 microM) was higher than the IC50 found for inhibition of the synaptosomal DA reuptake (0.8 microM). This finding extended the same observation previously described for the 5-HTergic system to the DAergic system, confirming that the inhibition of monoamine reuptake is due to a different mechanism than that of synthetic antidepressants. Hypericin showed micromolar affinities for both NPY-Y1 and Y2 receptors and for sigma receptors (IC50 3-4 microM). These hypericin activities might be of interest because NPY and sigma receptors have been associated with anxiety disorders, depressive illnesses and ethanol consumption. However, they were present at relatively high hypericin concentrations, and were also light-dependent (i.e. the IC50 values increased when binding assays were carried out in the dark). Thus, our in vitro binding results may suggest that either the pharmacological effects of SJW are due to other molecules than hypericin or hyperforin (other constituents or active metabolites), or that the mechanism of action is different from those that have been considered up to now.
 ...
PMID:In vitro binding studies with two hypericum perforatum extracts--hyperforin, hypericin and biapigenin--on 5-HT6, 5-HT7, GABA(A)/benzodiazepine, sigma, NPY-Y1/Y2 receptors and dopamine transporters. 1151 75

Hypericum perforatum L. (St. John's wort) is an herbal remedy widely used in the treatment of mild to moderate depression. Hypericin, a photosensitive napthodianthrone, is believed to be the compound responsible for reversing the depression symptoms. In this study, novel in vitro cell culture systems of H. perforatum were used to monitor the effect of elicitation on cell growth and production of hypericin. A dramatic increase in cell growth and hypericin production was observed after exposure to jasmonic acid (JA). However, other elicitors such as salicylic acid (SA) and fungal cell wall elicitors failed to show any stimulatory effect on either cell growth or hypericin production. Cell cultures treated with JA and incubated in the dark showed increased growth and hypericin production as compared to the cultures grown under light conditions. Jasmonate induction in dark conditions played an important role in growth and hypericin production in cell suspension cultures, to our knowledge an undocumented observation.
 ...
PMID:Jasmonic acid-induced hypericin production in cell suspension cultures of Hypericum perforatum L. (St. John's wort). 1203 48

Saint John's wort (Hypericum perforatum L.) is a herbal remedy that is effective in the treatment of mild to moderate depression. In traditional folk medicine, oily extracts of St. John's wort are used for topical treatment of wounds, burns and myalgia. The lipophilic phloroglucin-derivative hyperforin has antibacterial and antiinflammatory effects. These effects could be of relevance in topical treatment of infected wounds and other dermatoses, but no studies have been conducted so far. The naphtodianthrone hypericin is a photodtodynamic active substance that kills tumor cells via the induction of apoptosis. Hypericin also displays antiviral activity in vitro. In vivo, intravenous or oral treatment with hypericin of HIV-infected subjects did not result in a reduction of the virus load. Most of the patients treated with hypericin experienced phototoxicity. Similar phototoxic symptoms ("hypericism") have been observed in grazing animals ingesting large amounts of St. John's wort. In contrast, antidepressant medication with St. John's wort usually does not produce phototoxic symptoms. Recent pharmacokinetic studies suggest that the phototoxic threshold level of hypericin is not reached with dosages used for the oral treatment of depression. However, very recent reports demonstrated interactions of St. John's wort with other drugs such as digoxin, indinavir and cyclosporin. Blood levels of these drugs were dramatically decreased by St. John's wort. This should be considered in the treatment of skin conditions with antiviral drugs or cyclosporin.
 ...
PMID:[St. John's wort (Hypericum perforatum L.). A plant with relevance for dermatology]. 1206 42

St. John's wort (Hypericum perforatum L.) is widely used for the treatment of mild to moderately severe depression. However, the nature of its active principles and the exact mode of antidepressant action are still unknown. It has been suggested repeatedly in preclinical and clinical studies that the content of the acylphloroglucinol hyperforin decisively contributes to the antidepressant efficacy of St. John's wort extracts. Experimental studies in vivo also indicate that the naphthodianthrone hypericin may reduce the activity of the hypothalamic-pituitary-adrenal axis. Exacerbated hypothalamic-pituitary-adrenal activity has often been associated with depressive states in patients. Corticotropin-releasing factor (CRF) seems to be a major determinant in the regulation of the hypothalamic-pituitary-adrenal activity via activation of CRF(1) receptors. In the present study, we investigated the CRF(1) receptor antagonist activity of three main constituents of St. John's wort (hypericin, pseudohypericin and hyperforin) by measuring their effect on CRF-stimulated cAMP formation in recombinant Chinese hamster ovary (CHO) cells. As a selectivity test, the compounds were also tested against calcitonin in the same cells. Of the three compounds tested, only pseudohypericin selectively antagonised CRF (K(B) 0.76 microM). Hypericin and hyperforin affected both CRF and calcitonin with similar potencies and the same type of behaviour (competitive antagonism for hypericin, noncompetitive for hyperforin). It is concluded that pseudohypericin is the only real CRF(1) receptor antagonist of the three constituents tested. In addition, evidence is provided that beside hyperforin, both pseudohypericin and hypericin are implicated in the antidepressant efficacy of St. John's wort.
 ...
PMID:Antagonist effect of pseudohypericin at CRF1 receptors. 1250 80

A major gene termed Hyp-1 encoding for hypericin (HyH) biosynthesis was cloned and characterized from Hypericum perforatum (St. John's wort) cell cultures. H. perforatum leaves are widely used as an herbal remedy in the treatment of mild to moderate depression. Hypericin, a photosensitive and red-colored naphthodianthrone, has been reported as the bioactive compound responsible for reversing the depression symptoms. In this study a novel red-color-based colony screening method for examining a cDNA library (lambda-TriplEX2) derived from H. perforatum cell cultures revealed the gene responsible for hypericin biosynthesis after the administration of emodin, a precursor of hypericin. The selected clones were expressed in Escherichia coli (BM 25.8 line) and were further screened for biosynthesis of emodin to hypericin, which resulted in an 84.6% conversion. The full-length cDNA sequence of Hyp-1 is 782 nucleotides in length with an open reading frame of 477 nucleotides coding for a protein of 159 amino acids, with a 45.1% homology to Bet.v.1 class allergens. Reverse transcriptase-PCR analysis showed high levels of Hyp-1 transcripts in dark-grown cell cultures compared with the levels in light-grown cell cultures and leaves. Southern blot analysis showed the presence of a single Hyp-1 gene in H. perforatum. Furthermore, Hyp-1 was expressed with a His6 affinity tag linked to its N terminal region using the expression vector pET-28a, and the recombinant Hyp-1 protein was able to convert HyH from emodin under in vitro conditions. HyH product inhibition was observed with emodin analogues, rhein, rhein methyl ester, and DNA3-55-1. Our results demonstrate a direct and complex conversion of emodin to HyH that is solely catalyzed by Hyp-1, a Bet.v.1 class allergen from H. perforatum.
 ...
PMID:Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John's wort (Hypericum perforatum L.). 1279 79


1 2 Next >>