High-performance liquid chromatography measurement of hyperforin and its reduced derivatives in rodent plasma

Rozio, Marco; Fracasso, Claudia; Riva, Antonella; Morazzoni, P.; Caccia, Silvio

doi:10.1016/j.jchromb.2004.10.015

Cited by 11 publications

(12 citation statements)

References 26 publications

(41 reference statements)

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“…At a higher dose (12.5 mg/kg) hyperforin brain concentrations amounted to only about 0.06 µM, or about 4% of the equivalent systemic exposure; these concentrations were possibly entirely related to hyperforin's effective contribution from blood, allowing for at least 10 µL/g of residual blood in the brain [38,50 ]. Similar findings have been reported after single and repeated oral doses of tetrahydrohyperforin and octahydrohyperforin in rats and mice, suggesting that the exchange between blood and brain is relatively restricted for this class of potential antidepressants [51]. As for hypericin and pseudohypericin, it remains to be established whether one or more metabolites of hyperforin and its reduced derivatives are able to enter the brain, interacting with high affinities with the classic neurotransmitter transporters and receptors believed to be involved in the etiology of depression.…”

Section: Concentrations At Supposed Site Of Actionsupporting

confidence: 71%

“…However, the poor stability of hyperforin when extracted from the herb and exposed to light and air, and its ease to oxidation certainly complicates the preparation of pharmaceutical and nutritional formulations of Hypericum perforatum whose pharmacological activities may be rapidly lost during storage [48]. This has led to the synthesis of more stable analogues, including esters and reduced derivatives of hyperforin which have undergone preliminary preclinical evaluation as potential antidepressants [49][50][51].…”

Section: Antidepressant-like Componentsmentioning

confidence: 99%

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Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

Caccia

2005

CDM

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Extracts of Hypericum perforatum are becoming increasingly popular for the treatment of mild to moderate depression, despite the lack of consensus on their efficacy. Although the mechanism(s) of this action are still debated, several components, including the naphthodianthrones hypericin and pseudohypericin, the acylphloroglucinol hyperforin and some flavonols, are believed to play major roles in the antidepressant-like effects. Some of these also increase the expression of the P-glycoprotein transporter and others the expression of cytochrome P450 enzymes, possibly contributing to the interactions involving the extracts and conventional drugs. However, few pharmacokinetic studies of naphthodianthrones and hyperforin have appeared and none has yet evaluated the exposure to unchanged quercetin and its glycosides after intake of extracts. There are no formal pharmacokinetic studies in special populations. Bioavailability appears low, giving variable steady-state plasma concentrations, whose prediction may be complicated by non-linearity for hypericin and hyperforin. Data on tissue distribution are scarce, and it appears that hypericin and hyperforin do not reach the central nervous system in appreciable concentrations in animals. Clearance is low-intermediate, with little or no unchanged compounds excreted with urine. Although some potentially active conjugated metabolites have been identified for quercetin and its glycosides after intake of authentic compounds or flavonol-rich foods, these too have been characterised little with regard to their pharmacokinetics and central activities. Thus, further pharmacokinetic and pharmacodynamic studies of the main components and their metabolites are urgently needed to clarify the role of each constituent and provide more rational and safe regimens for people preferring "natural" drugs.

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Section: Concentrations At Supposed Site Of Actionsupporting

confidence: 71%

Section: Antidepressant-like Componentsmentioning

confidence: 99%

Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

Caccia

2005

CDM

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“…Hyperforin has been found effective as an antidepressant, antiinflammatory, analgesic, and diuretic agent, and therefore has been used medicinally for a long time [28,47,48]. In the present study, we tested the effect of IDN5706, which shows a higher stability and has an increased bioavailability as compared to hyperforin [49].…”

Section: Discussionmentioning

confidence: 99%

Tetrahydrohyperforin Increases Adult Hippocampal Neurogenesis in Wild-Type and APPswe/PS1ΔE9 Mice

Abbott

Toledo

Aranguiz

et al. 2013

JAD

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Tetrahydrohyperforin (IDN5706), a semi-synthetic derivative of hyperforin, has shown neuroprotective properties preventing the impairment of synaptic plasticity and cognitive decline in an in vivo model of Alzheimer's disease (AD). Considering the reported role of adult neurogenesis in the plasticity of the hippocampal network, we investigated whether IDN5706 affects adult neurogenesis and hippocampal function. In hippocampal progenitors cultured from adult rats, IDN5706 increased proliferation. Moreover, treatment with IDN5706 for 4 weeks increased cell proliferation in the subgranular zone (SGZ) of the hippocampus in 2 month-old wild-type mice in vivo. As determined by double labeling with BrdU and neuronal markers, IDN5706 treatment increased the number of immature neurons and newborn mature neurons in the adult dentate gyrus. In addition, IDN5706 treatment improved long-term memory in a hippocampal-dependent spatial memory task. Finally, IDN5706 treatment increased cell proliferation and neural commitment in the SGZ of the double transgenic APPswe/PS1ΔE9 mouse model of AD. These results indicate that IDN5706 increases adult hippocampal neurogenesis and may have therapeutic value in neurological disorders in which adult neurogenesis is impaired.

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“…IDN 5706 is a hyperforin's semi synthetic derivative that was selected from a spectrum of derivatives of hyperforin and hyperforin itself because of its better stability (due to its low possibility to suffer polymeric deterioration, a well known characteristic of the phloroglucinoils) and because of a better oral bioavailability [26].The analysis of the size of amyloid plaques present in brain indicated that treatment with IDN5706 reduces the amount of big plaques detected by Th-S. The detection of A aggregates with antibodies did not show difference with the mice treated with IDN5706, probably because the total levels did not change after treatment.…”

Section: Discussionmentioning

confidence: 99%

The Hyperforin Derivative IDN5706 Occludes Spatial Memory Impairments and Neuropathological Changes in a Double Transgenic Alzheimers Mouse Model

Cerpa¹,

Hancke²,

Morazzoni³

et al. 2010

CAR

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The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropathology, learning and memory in a double transgenic (APPswe, PS-1dE9) mouse model of AD. Results indicate that, IDN5706 alleviates memory decline induced by amyloid-beta (Abeta) deposits as indicated by the Morris water maze paradigm. Moreover, the analysis of Abeta deposits by immunodetection and thioflavin-S staining of brain sections, only reveals a decrease in the frequency of the larger-size Abeta deposits, suggesting that IDN5706 affected the turnover of amyloid plaques. Immunohistochemical analysis, using GFAP and n-Tyrosine indicated that the hyperforin derivative prevents the inflammatory astrocytic reaction and the oxidative damage triggered by high Abeta deposit levels. We conclude that the hyperforin derivative, IDN5706, has therapeutic potential for prevention and treatment of AD.

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High-performance liquid chromatography measurement of hyperforin and its reduced derivatives in rodent plasma

Cited by 11 publications

References 26 publications

Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

Antidepressant-Like Components of Hypericum perforatum Extracts: An Overview of Their Pharmacokinetics and Metabolism

Tetrahydrohyperforin Increases Adult Hippocampal Neurogenesis in Wild-Type and APPswe/PS1ΔE9 Mice

The Hyperforin Derivative IDN5706 Occludes Spatial Memory Impairments and Neuropathological Changes in a Double Transgenic Alzheimers Mouse Model

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