Novel neurological and immunological targets for salicylate-based phytopharmaceuticals and for the anti-depressant imipramine.

Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses.

Compensatory weight gain due to dopaminergic hypofunction: new evidence and own incidental observations.

There is increasing evidence for a role of dopamine in the development of obesity. More specifically, dopaminergic hypofunction might lead to (over)compensatory food intake. Overeating and resulting weight gain may be induced by genetic predisposition for lower dopaminergic activity, but might also be a behavioral mechanism of compensating for decreased dopamine signaling after dopaminergic overstimulation, for example after smoking cessation or overconsumption of high palatable food.

Better than normal: improved formation of long-term spatial memory in healthy rats treated with levodopa.

Dopaminergic signaling modulates learning and memory. Consequently, treatment with the dopamine precursor levodopa ameliorates memory deficits in murine models of Alzheimer's disease. In healthy humans, administration of L-DOPA increases learning and memory.

Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties.

Extracts of Valeriana officinalis L. s.l.

Sedating effects of Humulus lupulus L. extracts.

It was the aim of the study to check ethanolic and CO2 extracts from Humulus lupulus for sedating activity. Both preparations reduced the spontaneous locomotor activity, increased the ketamine-induced sleeping time and reduced body temperature, confirming a central sedating effect. No indications of anxiolytic activity were found in the elevated plus maze test for any of the test preparations.

Reduction of voluntary ethanol consumption in alcohol-preferring Alko alcohol (AA) rats by desoxypeganine and galanthamine.

The effects of desoxypeganine, an alkaloid from Peganum harmala L., and of galanthamine, an alkaloid from Galanthus nivalis L., on voluntary ethanol consumption were investigated in female Alko alcohol (AA) rats.

Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats.

Extracts from the plant Lycopus europaeus L. are traditionally used in mild forms of hyperthyroidism. High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations.

Flavonoids of St. John's Wort reduce HPA axis function in the rat.

A common biological alteration in patients with major depression is the activation of the hypothalamic-pituitary-adrenal (HPA) axis, manifested as hypersecretion of adrenocorticotropic hormone (ACTH) and cortisol. The hyperactivity of the HPA axis in depressed patients can be corrected during clinically effective therapy with standard antidepressant drugs such as imipramine, indicating that the HPA axis may be an important target for antidepressant action. We previously showed that a methanolic extract of St.

Extracts of St. John's wort and various constituents affect beta-adrenergic binding in rat frontal cortex.

The present study was designed to get further insight into the mode of antidepressant action of extracts prepared from St. John's wort (SJW) and relevant active constituents. Down-regulation of central beta-adrenergic receptors (beta-AR's) has been widely considered a common biochemical marker of antidepressant efficacy.

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.

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.

Step by step removal of hyperforin and hypericin: activity profile of different Hypericum preparations in behavioral models.

Herbal extracts of Hypericum perforatum L. (St. John's wort, SJW) are now successfully competing for status as a standard antidepressant therapy.

Plasma levels of hypericin in presence of procyanidin B2 and hyperoside: a pharmacokinetic study in rats.

The biological evaluation of hypericin in various test models is hampered by its poor water solubility. In former studies we have shown that the water solubility of hypericin was remarkably enhanced in the presence of the procyanidins or flavonol glycosides of Hypericum extract. The present pharmacokinetic study was designed to find out whether the improved water solubility in the presence of procyanidin B2 or hyperoside is correlated to increased plasma levels of hypericin.

Cimicifuga extract BNO 1055: reduction of hot flushes and hints on antidepressant activity.

Ethanolic- and isopropanolic-aqueous extracts of Cimicifuga racemosa are used for the treatment of climacteric complaints. As hot flushes and psychic complaints seem to be special targets for Cimicifuga extracts in clinical studies, these parameters were studied in experimental animals. Hot flush equivalents were measured in castrated rats as a quick increase in peripheral temperature with the aid of a transmitter implanted subcutaneously on the ventral side.

[Pharmacologic and clinical studies using Cimicifuga racemosa in climacteric complaints].

Climacteric complaints are caused by a decrease in estrogen production and are characterized by neurovegetative and psychic complaints. Hot flushes represent the leading symptom, in addition excitability, irritability and sleep disturbances are reported. These complaints are usually treated with estrogens, but extracts of Cimicifuga racemosa are used for this indication, too.

Long-term effects of St. John's wort and hypericin on monoamine levels in rat hypothalamus and hippocampus.

Hypericum perforatum L. (St. John's wort) is one of the leading psychotherapeutic phytomedicines and, because of this, great effort has been devoted to clarifying its mechanism of action.

St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats.

Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situhybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment.

Clinical studies have demonstrated the antidepressant efficacy of Hypericum (St. John's wort) extracts comparable to tricyclic antidepressants such as imipramine. We examined the effects of Hypericum extract and hypericin, one active constituent, in the forced swimming test (FST) after treatment repeated for 14 days.

Neurotransmitter concentrations and binding at dopamine receptors in rats after maternal exposure to 3,4,3',4'-tetrachlorobiphenyl: the role of reduced thyroid hormone concentrations.

Polychlorinated biphenyls (PCBs) are environmental contaminants, which accumulate in the food chain and are transferred to the offspring during prenatal development through the placenta and postnatally via breast milk. It is reported that PCBs exert effects on thyroid hormone levels and brain neurotransmitter levels. Both actions may alter neuronal development.

Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test.

It has been shown recently that a flavonoid fraction (fraction II) obtained from a crude extract of Hypericum perforatum (St. John's Wort) was remarkably active in the forced swimming test (FST). Fraction II was further separated using MLCCC to give fractions IIa and IIb.

Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid.

Hydroxycinnamic acid esters of fukiic acid and piscidic acid were isolated from a 50% ethanolic extract obtained from the rhizomes of Cimicifuga racemosa (Ranunculaceae). Besides 2-E-caffeoylfukiic acid (fukinolic acid), 2-E-feruloylfukiic acid (cimicifugic acid A), 2-E-isoferuloylfukiic acid (cimicifugic acid B), 2-E-feruloylpiscidic acid (cimicifugic acid E) and 2-E-isoferuloylpiscidic acid (cimicifugic acid F), free caffeic, ferulic and isoferulic acids were isolated. The estrogenic activity of fukinolic acid was shown by increased proliferation (126% at 5 x 10(-8) M) of an estrogen dependent MCF-7 cell system with reference to estradiol (120% at 10(-10) M).

Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test.

It has been shown recently that the fraction IIIc of a crude extract of Hypericum perforatum, (St. John's wort) that contained both hypericin (1) and pseudohypericin (2), was remarkably active in the rats forced swimming test (FST) after Porsolt. However, neither of the naphthodianthrones isolated from this fraction were sufficiently effective when administered suspended in water.

Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity.

A commercially available extract of the aerial parts of Hypericum perforatum, LI 160, showed pronounced activity in selected animal bioassays. These include the forced swimming test (FST) and the tail suspension test, used to determine antidepressant activity, and tests indicating activity on the central nervous system, such as body temperature and ketamine induced sleeping time. The counteracting effects of drugs known to interfere with the central dopaminergic system strongly suggested that dopamine mediated activity is important for the activity of the extract.

Effects of maternal exposure to 3,3',4,4'-tetrachlorobiphenyl or propylthiouracil in rats trained to discriminate apomorphine from saline.

In the present experiment drug discrimination was examined in rats after maternal exposure to 3,3',4,4'-tetrachlorobiphenyl (PCB 77) using apomorphine (APO) as the training drug at a dose reported to act on dopamine D2 receptors. A group with maternal exposure to 6n-propyl-2-thiouracil (PTU) was included as a positive control for effects induced by PCB 77 on thyroid hormones. On gestational day (GD) 19 reduced levels of free and total thyroxine (FT4, TT4) and free triiodothyronine (FT3) were detected in dams exposed to PCB 77 or PTU.

Thyrotropin expression in hypophyseal pars tuberalis-specific cells is 3,5,3'-triiodothyronine, thyrotropin-releasing hormone, and pit-1 independent.

The expression of TSH subunit genes (TSH alpha and -beta) in pituitary thyrotropes is primarily regulated via circulating thyroid hormone levels (T3) and the hypothalamic TRH. Hypophyseal pars tuberalis (PT)-specific cells also express both hormonal subunits of TSH, but do not resemble thyrotropes of the pars distalis (PD) with respect to their distinct morphology, secretion, and direct modulation of TSH expression by photoperiodic inputs and melatonin. To investigate whether this distinct regulation of TSH is related to a different molecular structure or different signaling cascades, we analyzed PT-specific TSH and its transcriptional regulation in ovine PT-specific cells.

Analysis of the components of Lycopus europaeus L. in body fluids during metabolism studies. Comparison of capillary electrophoresis and high-performance liquid chromatography.

During pharmacokinetic studies with extracts obtained from medicinally used plants, analysis in body fluids is mainly performed by HPLC, an established separation method. In this paper high-performance capillary electrophoresis (HPCE) is investigated for its ability to separate such complex extracts. Crude extracts of Lycopus europaeus L.