Inhibition of Synaptosomal Uptake of 3H-L-glutamate and 3H-GABA by Hyperforin, a Major Constituent of St. John's Wort The Role of Amiloride Sensitive Sodium Conductive Pathways

Wonnemann, Meinolf

doi:10.1016/s0893-133x(00)00102-0

Cited by 122 publications

(82 citation statements)

References 40 publications

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“…However, hyperforin exerts this effect through a different mechanism compared with synthetic antidepressants. It shows a broad-band reuptake inhibition of many neurotransmitters such as serotonin, norepinephrine and dopamine at concentrations between 80 nM and 200 nM (Muller et al, 1998), and gamma-aminobutyric acid (GABA) and glutamate at concentrations between 100 nM and 1000 nM (Wonnemann et al, 2000). Follow-up studies provided a possible explanation for this unique mechanism of action for hyperforin.…”

Section: Mechanisms Of Action For Hyperforin As An Antidepressant Commentioning

confidence: 99%

Hyperforin promotes mitochondrial function and development of oligodendrocytes

Wang

Zhang

et al. 2011

Journal of Neurochemistry

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Major depressive disorder is a common severe psychiatric disorder with unknown etiology. Recent studies show that the loss and malfunction of oligodendrocytes are closely related to the neuropathological changes in depression, which can be reversed by antidepressant treatment. St. John's wort is an effective and safe herbal treatment for depression in several clinical trials. However, the underlying mechanism of its therapeutic effects is unclear. In this study, we evaluated the effects of hyperforin, a iii ACKNOWLEDGEMENTS

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Section: Mechanisms Of Action For Hyperforin As An Antidepressant Commentioning

confidence: 99%

Hyperforin promotes mitochondrial function and development of oligodendrocytes

Wang

Zhang

et al. 2011

Journal of Neurochemistry

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“…Hyperforin has been shown to be an uptake inhibitor of 5-HT, dopamine, norepinephrine, GABA and -glutamate in synaptosomal preparations (Chatterjee et al 1998a ;Wonnemann et al 2000), and to inhibit 5-HT uptake in rat peritoneal cells in a dose-dependent manner (Chatterjee et al 1998b). Studies have also described discrepancies between observed and theoretical IC50 values, indicating that hyperforin is not the only component of hypericum extract that is responsible for the observed effects (Chatterjee et al 1998b ;Gobbi et al 1999).…”

Section: Antidepressant Activitymentioning

confidence: 99%

St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties

Barnes

Anderson

Phillipson

2001

Journal of Pharmacy and Pharmacology

694

462

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The chemical composition of St. John's wort has been well-studied. Documented pharmacological activities, including antidepressant, antiviral, and antibacterial effects, provide supporting evidence for several of the traditional uses stated for St John's wort. Many pharmacological activities appear to be attributable to hypericin and to the flavonoid constituents ; hypericin is also reported to be responsible for the photosensitive reactions that have been documented for St. John's wort. With regard to the antidepressant effects of St John's wort, hyperforin, rather than hypericin as originally thought, has emerged as one of the major constituents responsible for antidepressant activity. Further research is required to determine which other constituents contribute to the antidepressant effect.Evidence from randomised controlled trials has confirmed the efficacy of St John's wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomised controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression. There is still a need for further trials to assess the efficacy of St John's wort extracts, compared with that of standard antidepressants, particularly newer antidepressant agents, such as the selective serotonin reuptake inhibitors (recent comparative studies with fluoxetine and sertraline have been conducted). Also, there is a need for further studies in well-defined groups of patients, in different types of depression, and conducted over longer periods in order to determine longterm safety. St John's wort does appear to have a more favourable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication.Concerns have been raised over interactions between St John's wort and certain prescribed medicines (including warfarin, ciclosporin, theophylline, digoxin, HIV protease inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, triptans, oral contraceptives) ; advice is that patients taking these medicines should stop taking St John's wort, generally after seeking professional advice as dose adjustment of conventional treatment may be necessary.

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“…Later studies revealed the potent antidepressant activity of hyperforin, which was similar to other common antidepressant treatments (Chatterjee et al 1998;Laakmann et al 1998;Di Carlo et al 2001) and clinical trials using Hypericum extracts indicate that antidepressant activity of St. John's wort depends on hyperforin concentration (Laakmann et al 1998). In brain tissues, hyperforin increases the concentration of neurotransmitters such as serotonin, norepinephrine, dopamine, GABA, and glutamate in the synaptic space (Chatterjee et al 1998;Wonnemann et al 2000;Marsh and Davies 2002;Treiber et al 2005). The transport of neurotransmitters is driven by cellular Na + gradients and operated by Na + co-transport (Malandro and Kilberg 1996).…”

Section: Neuroregulatory Molecules In Plantsmentioning

confidence: 87%

Neurotransmitters, neuroregulators and neurotoxins in the life of plants

Cao¹,

Cole²,

Murch³

2006

Can. J. Plant Sci.

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Cao, J., Cole, I. B. and Murch, S. J. 2006. Neurotransmitters, neuroregulators and neurotoxins in the life of plants. Can. J. Plant Sci. 86: 1183-1188. Recent evidence has shown that neurologically active compounds play an important role in the physiology of higher plants. The human neurotransmitter melatonin (N-acetyl-5-methoxytryptamine) has been found in more than 140 different plant species and is associated with flower and seed development, reproductive capacity and root growth. Hyperforin, once thought to be characteristic of St. John's wort (Hypericum perforatum L.), has now been found in several other plant species and preliminary findings indicate that it may function as a modulator of plant cell polarity and ion flow. The excitotoxin, β-methylamino-L-alanine, has been used to selectively isolate glutamate receptor mutants in Arabidopsis, and these studies are leading to new understandings of plant cell development. The study of these and other plant neurochemicals may lead to a new understanding of plant signal transmission and the mechanisms by which plant cells sense, interpret and respond to environmental cues. Mots clés: Neuromédiateurs, mélatonine, hyperforine, plante médicinale Plant cells produce a wide range of common and uncommon chemical compounds that ensure the survival of the individual and the species. Most frequently, plant responsive compounds are thought of as secondary metabolites, compounds that are not essential for the growth and development of the plant, but that accumulate in response to environmental stressors. However, there is another group of phytochemicals that includes compounds historically classified as primary or secondary metabolites that are essential for the reallocation of resources in plants in response to changing environmental factors. Neurologically active compounds fall into this mixed category and include such diverse examples as indoleacetic acid, caffeine, epinephrine, acetylcholine, opiates, nicotine, levodopa, serotonin, melatonin, hyperforin and many others. In mammalian systems, neurologically active compounds mediate brain function so that external stimuli are translated into immediate responses. The human neurotransmitter melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous, highly conserved molecule associated with timing of circadian rhythms in many organisms, including higher plants. Other compounds such as hyperforin, now isolated from several plant species, may function as serotonin transport inhibitors or nonspecific cation channel activators in human brains and potentially in higher plants. A different group of neuroregulatory molecules produced by plants overstimulate human neurons, resulting in neuronal cell damage and death. Excitotoxins such as β-methylamino-L-alanine not only affect human health but are also regulatory molecules redirecting plant growth. Plants lack the "flight or flight" response common

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Inhibition of Synaptosomal Uptake of 3H-L-glutamate and 3H-GABA by Hyperforin, a Major Constituent of St. John's Wort The Role of Amiloride Sensitive Sodium Conductive Pathways

Cited by 122 publications

References 40 publications

Hyperforin promotes mitochondrial function and development of oligodendrocytes

Hyperforin promotes mitochondrial function and development of oligodendrocytes

St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties

Neurotransmitters, neuroregulators and neurotoxins in the life of plants

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