Effects of Hypericum Extract (LI 160) in Biochemical Models of Antidepressant Activity

Müller, Wernér E.G.; Rolli, Melanie; Schäfer, Carolin; Hafner, Ulrike

doi:10.1055/s-2007-979528

Cited by 280 publications

(182 citation statements)

References 8 publications

(12 reference statements)

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“…18 Hypericum's potency on monoamine re-uptake inhibition is remarkable as previous studies by the same authors have shown that classical antidepressants such as imipramine were also active in these systems with IC 50 values around 20 nmol L −1 for the 5-HT and NA uptake systems. 17 Comparable potencies were also found in the literature for other antidepressants (Table 2). More recently Neary and Bu 21 reported the first study on the effects of hypericum on 5-HT and NA transport in intact neuronal cells.…”

Section: Experimental Pharmacology Of Hypericumsupporting

confidence: 59%

“…[24][25][26] Quercetin and Quercitrin, both flavonoide aglykone constituents of hypericum extract have also been shown to inhibit MAO-A, 27 although a therapeutic action of these compounds remains questionable because of their low plasma levels. Supporting the negative findings, studies by Muller et al 17 showed that the IC 50 values of hypericum as an inhibitor of MAO-A or MAO-B activity exceeded 100 g ml −1 (100 times higher than the IC 50 for inhibition of monoamine re-uptake), making it unlikely that both these mechanisms are involved in the antidepressant action of hypericum. However the effect of hypericum on MAO-A and MAO-B inhibition may be dose-related as a study by Kako et al 28 suggests that extremely high doses of hypericum are needed to actively inhibit MAO.…”

Section: Experimental Pharmacology Of Hypericummentioning

confidence: 93%

“…Effects on monoamine re-uptake Recent reports by Rolli et al 16 and Muller et al 17 showed that a clinically used hypericum extract (LI 160) like conventional antidepressants, concentration dependently and potently inhibited the synaptic reuptake of 5-HT, NA and DA with an IC 50 around 17 The hyperforin present in the alcoholic extract (LI 160) was also shown to inhibit the synaptic uptake of 5-HT, NA and DA in a similar concentration range (24-150 nmol L −1 ) ( Table 2). 18 In contrast hypericin, a major constituent of hypericum, that was originally thought to be important for antidepressant action, had no effect on synaptic uptake of monoamines.…”

Section: Experimental Pharmacology Of Hypericummentioning

confidence: 98%

“…An important consideration is the relevance of these pharmacological effects seen in animals to the therapeutic doses used in clinical studies for the treatment 17,22 Similarly, the dose of hypericum used by most studies is 10-20 times the average clinical dose used for mild-to-moderate depression. 3 However, under these conditions most of the pharmacological effects observed with antidepressants are consistent.…”

Section: Experimental Pharmacology Of Hypericummentioning

confidence: 99%

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

Nathan

1999

Mol Psychiatry

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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.

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Section: Experimental Pharmacology Of Hypericumsupporting

confidence: 59%

Section: Experimental Pharmacology Of Hypericummentioning

confidence: 93%

Section: Experimental Pharmacology Of Hypericummentioning

confidence: 98%

Section: Experimental Pharmacology Of Hypericummentioning

confidence: 99%

See 2 more Smart Citations

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

Nathan

1999

Mol Psychiatry

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“…The pharmacological activity of SJW extracts has recently been reviewed (Butterweck, 2003;Greeson et al, 2001;Nathan, 1999). Reports about the antidepressant activity of SJW extracts and their constituents both in vivo and in vitro have been published (Baureithel et al, 1997;Butterweck et al, 1997Butterweck et al, , 1998Butterweck et al, , 2000Butterweck et al, , 2001aButterweck et al, , b, 2002Calapai et al, 1999;Chatterjee et al, 1996Chatterjee et al, , 1998aDi Matteo et al, 2000;Franklin and Cowen, 2001;Gobbi et al, 1999Gobbi et al, , 2001Müller et al, 1997Müller et al, , 1998Müller et al, , 2001Simmen et al, 1999Simmen et al, , 2001Singer et al, 1999;Wonnemann et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

Butterweck

Winterhoff²,

Herkenham

2003

Neuropsychopharmacol

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We previously showed that a methanolic extract of St John's wort (SJW) (Hypericum) and hypericin, one of its active constituents, both have delayed regulation of genes that are involved in the control of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperforin, another constituent of SJW, is active in vitro and has been proposed to be the active constituent for therapeutic efficacy in depression. We therefore examined if hyperforin has delayed effects on HPA axis control centers similar to those of Hypericum and hypericin. We used in situ hybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) oral administration of two hyperforin preparations, fluoxetine (positive control), and haloperidol (negative control) on the expression of genes involved in the regulation of the HPA axis. Fluoxetine (10 mg/kg) given daily for 8 weeks, but not 2 weeks, significantly decreased levels of corticotropinreleasing hormone (CRH) mRNA by 22% in the paraventricular nucleus (PVN) of the hypothalamus and tyrosine hydroxylase (TH) mRNA by 23% in the locus coeruleus. Fluoxetine increased levels of mineralocorticoid (MR) (17%), glucocorticoid (GR) (18%), and 5-HT 1A receptor (21%) mRNAs in the hippocampus at 8, but not 2, weeks. Comparable to haloperidol (1 mg/kg), neither the hyperforinrich CO 2 extract (27 mg/kg) nor hyperforin-trimethoxybenzoate (8 mg/kg) altered mRNA levels in brain structures relevant for HPA axis control at either time point. These data suggest that hyperforin and hyperforin derivatives are not involved in the regulation of genes that control HPA axis function.

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St John's Wort for Depression

Gaster¹,

Holroyd²

2000

Arch Intern Med

239

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T o address whether St John's wort is useful for the treatment of depression we attempted to retrieve all English-language articles with data on the efficacy, safety, and availability of St John's wort. Randomized, controlled, double-blind trials were selected and assessed for methodological quality using a standardized checklist, and data on pharmacology, cost, regulation, and safety were extracted. Eight studies were identified, found to be of generally good methodological quality, and determined to provide a modest amount of data to suggest that St John's wort is more effective than placebo in the treatment of mild to moderate depression. The absolute increased response rate with the use of St John's wort ranged from 23% to 55% higher than with placebo, but ranged from 6% to 18% lower compared with tricyclic antidepressants. More data are required to assess both its use in severe depression and its efficacy compared with other antidepressants. Rates of side effects were low. As a dietary supplement, St John's wort is currently largely unregulated, but the Food and Drug Administration is reviewing plans to tighten its regulatory oversight.Arch Intern Med. 2000;160:152-156

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Effects of Hypericum Extract (LI 160) in Biochemical Models of Antidepressant Activity

Cited by 280 publications

References 8 publications

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

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

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

St John's Wort for Depression

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