Biomedical subjects

H Winterhoff

Publications and source records attributed to H Winterhoff.

At least 19 recordsLinked to original sources

PubMed2006

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. This sedating activity could be attributed to three categories of constituents of lipophilic hops extracts. Though the alpha-bitter acids proved to the be most active constituents, the beta-bitter acids and the hop oil clearly contributed to the sedating activity of lipophilic Humulus extracts.

Animals↗

PubMed2004

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. Although previous studies have reported a beta-AR down-regulation for SJW extracts, in vivo studies that compare the effects of SJW extracts with those of relevant active constituents on beta-AR density have not been done yet. We used quantitative radioligand receptor-binding-studies to examine in rats the effects of short-term (2 wks) and long-term (8 wks) administration of different SJW extracts and constituents on beta-AR binding in rat frontal cortex. The effects were compared to those of the standard antidepressants imipramine and fluoxetine. [125I]CYP binding to beta-AR was found to be decreased after short as well as after long-term treatment with imipramine (36%, 40%). Short-term treatment with fluoxetine decreased the number of beta-adrenergic receptors (17%) while long-term treatment with fluoxetine elicited an increase (14%) in beta-AR-binding. This effect was comparable to that of the lipophilic CO2 extract which decreased beta-AR-binding (13%) after two weeks and slightly increased the number of beta-AR's after 8 weeks (9%). Short-term treatment with the methanolic SJW extract decreased beta-AR-binding (14%), no effects for this extract were observed after 8 weeks. Treatment with hypericin led to a significant down-regulation (13%) of beta-AR's in the frontal cortex after 8-weeks, but not after 2 weeks, while hyperforin (used as trimethoxybenzoate, TMB), and hyperoside were ineffective in both treatment paradigms. Compared to the SJW extracts and single compounds the effect of imipramine on beta-AR-binding was more pronounced in both treatment paradigms.

Animals↗

PubMed2004

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. John's Wort (SJW) and hypericin, one of its active constituents, both have delayed effects on the expression of genes that are involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis , whereas the phloroglucinol derivative hyperforin was inactive in the same model . Since flavonoids of SJW are also discussed as active constituents it was of interest to determine whether these compounds can modulate HPA axis function. Imipramine (15 mg/kg), hypericin (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated circulating plasma levels of ACTH and corticosterone by 40 - 70 %. However, none of the compounds tested had an effect on plasma ACTH and corticosterone levels after chronic treatment (daily gavage for 8 weeks). Our data suggest that besides hypericin, flavonoids of SJW play an important role in the modulation of HPA axis function. Furthermore, the results support the hypothesis that flavonoids are involved in the antidepressant effects of SJW.

Administration, Oral↗

PubMed2003

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. Plasma levels of hypericin in rats in the presence and absence of procyanidin B2 or hyperoside were determined by reversed phase HPLC using fluorimetric detection. Both compounds increased the oral bioavailability of hypericin by ca. 58 % (B2) and 34 % (hyperoside). Procyanidin B2 and hyperoside had a different influence on the plasma kinetics of hypericin; median maximal plasma levels of hypericin were detected after 360 min (C max : 8.6 ng/mL) for B2, and after 150 min (C max : 8.8 ng/mL) for hyperoside. It can be speculated that, when administered together with these compounds, a significant accumulation of hypericin in rat plasma in the presence of both polyphenols might be responsible for the observed increased in vivo activity.

Administration, Oral↗

PubMed2002

[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. Clinical studies gave evidence for the efficacy of Cimicifuga extracts in patients with climacteric symptoms. In pharmacological experiments Cimicifuga extracts exhibited organ specific estrogenic effects and were characterised as selective estrogen-receptor-modulators. In addition pronounced effects on the central nervous system were shown. Taking these relevant therapeutic properties into account further experimental and clinical studies seem to be necessary and promising.

Aged↗

PubMed2001

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. The aim of the present study was to investigate, if PCB-induced effects on concentrations of catecholamines and serotonin can be attributed to PCB-induced reductions in thyroid hormone concentrations. In addition, binding to dopamine D(1) and D(2) receptors was examined. Time-mated Wistar rats were treated prenatally with 1 mg 3,4,3',4'-tetrachlorobiphenyl (PCB 77)/kg bodyweight or the vehicle. A third group serving as the positive control received perinatally 5 mg propylthiouracil (PTU)/l drinking water. There were no overt toxic signs in dams or offspring. Thyroid hormone measurements demonstrated effects in dams and offspring up to postnatal day 40. In particular, total T(4) in serum and in the thyroid were decreased in PCB- and PTU-treated dams and offspring. Only PTU exposed rats exhibited significantly increased concentrations of TSH in the serum and pituitary. Measurement of neurotransmitters revealed changes in the PCB-exposed offspring at PND 40, while PTU-treatment was without effect. Dopamine and DOPAC were increased in the medial prefrontal cortex. In adulthood, there were no PCB-related effects on thyroid hormones and neurotransmitters. Binding studies of dopamine D1 and D2 receptors demonstrated that PCB and PTU had no influence on receptor concentration and affinity. Comparison of PCB 77 exposed offspring to PTU exposed offspring demonstrated differential effects on TSH and neurotransmitter levels, the latter result indicating that not all PCB-induced effects on the nervous system can be ascribed to decreases in thyroid hormone concentrations.

Journal Article↗

PubMed2001

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. Imipramine (15 mg kg(-1)), Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT(1A) receptor mRNA by 11-17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT(1A) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT(1A)mRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract.

Adrenal Glands↗

PubMed2001

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. It has recently been shown that hypericin was inactive in the FST after acute treatment, but remarkably active when solubilized by subfraction IIIc1 containing mainly procyanidin B2. Therefore, we investigated the cooperative effects of hypericin and procyanidin B2 after repeated treatment. Imipramine (15 mg/kg), Hypericum extract (500 mg/kg) and hypericin (0.1 mg/kg) given daily for 2 weeks significantly reduced immobility time in the FST. No differences were observed between animals receiving pure hypericin and those receiving hypericin in combination with procyanidin B2. As several antidepressants act on the neuroendocrine axis resulting in altered hormone concentrations, selected endocrine parameters were investigated after repeated treatment. Daily treatment with either imipramine, Hypericum extract or hypericin alone or in combination with procyanidin B2 for 14 days significantly decreased plasma ACTH and corticosterone levels. None of the substances had pronounced effects on plasma prolactin or LH levels. From our present data, we propose that cooperative effects of hypericin and procyanidin B2 are of important relevance for the acute, but not for the chronic effects of this polycylic quinone.

Adrenal Glands↗

PubMed2000

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. Both fractions proved to be active in the FST at different dosages. Further separation of fraction IIa by preparative HPLC yielded fraction IIa1 which mainly was composed of hyperoside, isoquercitrin, miquelianin and quercitrin, and fraction IIa2 which contained small amounts of hyperoside and astilbin, while most compounds were not known. Both fractions were active after acute treatment in the FST. Isolates obtained from these fractions including hyperoside, isoquercitrin, quercitrin, miquelianin, the aglycone quercetin and astilbin, were tested for activity in the FST. Except for quercetin, quercitrin and astilbin all compounds were active. To exclude false positive results in the FST the validity was checked in open field experiments and in the FST after 12 days of daily treatment.

Animals↗

PubMed1999

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).

Esters↗

PubMed1998

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. The solubility of 1 and 2 is remarkably increased in the presence of a fraction containing procyanidins, especially procyanidin B2, which is present also in the active Hypericum fraction IIIc. The cooperative effect of procyanidins significantly increased the in vivo effects of 1 and 2, which exhibited inverted U-shaped dose response curves, in the FST. The anti-immobility effect of solubilized 1 and 2 was antagonized by the dopamine antagonist sulpiride. These data indicate that naphthodianthrones are antidepressant constituents of H. perforatum and suggest that the dopaminergic system is involved in their action.

Animals↗

PubMed1997

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. In the offspring decreases in levels of FT4 and TT4 were found in both treated groups on postnatal day (PND) 21, while reductions of FT3 were observed only in the PTU group. PTU-treated rats needed more daily sessions for successful discrimination between apomorphine and saline. There were no differences between groups in generalization tests and sessions with the D2/D3 agonist quinpirole, the D2 antagonist haloperidol plus APO, or with the GABAergic drug pentobarbital and only minor differences in sessions with the D1 agonist SKF-38393. Differences between controls and groups exposed to PCB 77 or PTU were detected in a blocking test using the mixed serotonin 5-HT1A agonist and partial D2 antagonist buspirone. This outcome suggests long-lasting effects by developmental exposure to PCB 77 on the interaction between dopaminergic and serotonergic processes which may be mediated by effects on thyroid hormone levels.

Animals↗

PubMed1997

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. Dose-response experiments of the total extract and of fractions rich in flavonoids and napthodianthrones produced inverted U-shaped dose response curves.

Animals↗

PubMed1997

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. After construction of PT- and PD-specific complementary DNA (cDNA) libraries, the cloning and sequencing of several TSH alpha and -beta subunit clones revealed identical sizes and sequences for the translated and untranslated regions in both hypophyseal compartments. Transcription start site analysis also displayed three identical start sites for the transcription of TSH beta in PT and PD. After cloning of the ovine TRH receptor cDNA and a partial T3 receptor cDNA, in situ hybridization. Northern blot analysis, and PCR experiments showed that TRH and T3 receptors are not expressed in specific cells of the PT. The transcription factor Pit-1 that is involved in TSH expression of thyrotropes could only be detected in the PD. In additional experiments rats were treated with T4 or TRH, and subsequent in situ hybridization studies showed that TSH beta messenger RNA (mRNA) formation was not altered in the PT. In the PD, however, TSH beta mRNA was significantly reduced in the T4-treated group, but was enhanced in the TRH-treated group. We conclude that PT-specific cells of the pituitary are characterized by the transcription of TSH subunits that are identical to TSH expressed in thyrotropes of the PD. The absence of TRH, T3 receptor mRNA, and Pit-1, respectively, as well as the different reactions compared to PD thyrotropes in in vivo experiments lead to the conclusion that the expression of TSH in PT-specific cells of the pituitary is not regulated via the classical thyrotrope receptors and their intracellular pathways, but through a novel, photoperiod-dependent mechanism.

Animals↗

PubMed1995

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. (Lamiaceae) are traditionally used against mild forms of hyperthyroidism. The metabolism of a 70% ethanolic extract with respect to some of its individual main components (rosmarinic and caffeic acid, luteolin-7-glucoside) and a mixture of the pure compounds were investigated using isolated perfused rat liver. After solid-phase extraction metabolites were determined using HPCE and HPLC separation techniques. A buffer solution composed of 0.05 mol l-1 Na2HPO4 at pH 7.0 with 30% acetonitrile was found to be the most suitable electrolyte for HPCE separation. The best mobile phase for isocratic HPLC was 0.03% TFA-acetonitrile (82:18, v/v). Data obtained with HPCE are in good accordance with those from HPLC; HPCE, however, is clearly more rapid and simple to perform.

Animals↗

PubMed1995

The effect of Chelidonium majus herb extract on choleresis in the isolated perfused rat liver.

The total ethanolic extract, the phenolic and the alkaloidal fraction of the herb of Chelidonium majus L. (Papaveraceae) were tested for their choleretic activity using the isolated perfused rat liver. The total extract significantly caused chloresis by increasing the bile acid independent flow (BAIF); the observed weak activity of both fractions, tested each and as combination, however, was not significant.

Animals↗

PubMed1994

Effects of pentachlorophenol (PCP) on the pituitary and thyroidal hormone regulation in the rat.

Investigations on rats after repeated application of pentachlorophenol (PCP) should clarify whether thyroid side effects caused by this xenobiotic can be seen in a dose range which does not cause major toxic effects. Female rats of the Wistar strain were treated with 3 and 30 mg PCP/kg body wt. daily by gavage for 28 days. To assess the potential impact of impurities the study was performed both with pure and technical grade PCP at the dosage of 3 mg.kg-1.day-1, and at a level of 30 mg.kg-1.day-1 with pure PCP only. The effects in animals on normal iodine diet were compared to those in animals on a low iodine diet. No decrease of body wt. was noticed, only the liver weights were increased slightly in animals treated with 30 mg.kg-1.day-1 PCP. However distinct effects on thyroid hormones as well as on thyrotropin (TSH) were observed: a pronounced fall of circulating thyroxine (T4) and triiodothyronine (T3) levels was accompanied by lower levels of both free thyroid hormones and TSH, and the T4:T3 ratio was decreased in serum. Furthermore the intrathyroidal hormone stores were reduced. An interference of PCP at pituitary or hypothalamic level is assumed as a major mode of action. Additional effects of the test substance on peripheral conversion can be suspected.

Administration, Oral↗

PubMed1994

Endocrine effects of Lycopus europaeus L. following oral application.

Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents.

Animals↗