Posted by Larry Hoover on September 5, 2003, at 13:43:23
Pharmacopsychiatry. 2003 Jul;36(4):161-4.
Sub-chronic Treatment Effects of an Extract of Hypericum perforatum (St. John's Wort, Li 160) on Neuroendocrine Responses to the 5-T2A Agonist, DOI in the Rat.Franklin M.
University of Oxford Department of Psychiatry, Warneford Hospital Oxford, UK. michael.franklin@psychiatry.ox.ac.uk
Clinical studies have demonstrated the antidepressant efficacy of LI 160 extracts, which is comparable to antidepressants such as imipramine. The study was undertaken to assess the sub-chronic effects of LI 160 extract on plasma corticosterone and prolactin (PRL) responses to the post-synaptic 5-HT 2A receptor agonist, 2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), in the male rat. Results show that sub-chronic treatment with the LI 160 extract reduced corticosterone and PRL responses to DOI. LI 160 may modify brain 5-HT function in the rat, possibly by reducing the sensitivity of central 5-HT 2A receptors. This may be a result of decreased receptor expression, signal transduction or intracellular messengers. These findings could be relevant to the therapeutic efficacy of St. John's wort.
Pharmacol Biochem Behav. 2003 Jun;75(3):593-606.Plant derivatives in the treatment of alcohol dependency.
Rezvani AH, Overstreet DH, Perfumi M, Massi M.
Department of Psychiatry, Duke University Medical Center, Box 3412, Durham, NC 27710, USA. Azadi@duke.edu
The present review summarizes the findings of the effects of extracts of purified compounds from several plants on alcohol intake in alcohol-preferring rats. These include St. John's wort (Hypericum perforatum, HPE), kudzu (Pueraria lobata) and ibogaine (Tabernanthe iboga). Alcohol-preferring (P), Marchigian Sardinian (msP), high-alcohol-drinking (HAD), Fawn-Hooded (FH) rats were allowed to drink alcohol or water voluntarily to establish baseline levels. Pure compounds (puerarin, daidzin, daidzein or analogs) isolated from kudzu, extracts from HPE or ibogaine and its analog were given by either intraperitoneal or oral administration. After acute administration, all agents dose-dependently reduced alcohol intake with minimal effects on food intake. Puerarin and HPE were also effective following chronic treatment. Overall, it is clear that pure compounds (daidzin, puerarin), extracts from St. John's wort, ibogaine and an ibogaine analog suppress alcohol intake in animal models of excessive drinking with minimal effects on other appetitive behaviors. Although the true mechanisms of action of these compounds on alcohol intake are not fully understood, with the current information, it appears that these compounds exert their effects by modulating several neuronal systems implicated in drinking behavior. However, their role in the future of pharmacotherapy for alcoholism will depend upon the outcome of carefully conducted clinical trials.
Pharmacol Res. 2003 Aug;48(2):199-207.
Effects of Hypericum perforatum and paroxetine on rat performance in the elevated T-maze.Beijamini V, Andreatini R.
Departamento de Farmacologia, Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Setor de Ciencias Biologicas, Centro Politecnico, Universidade Federal do Parana, P.O. Box 19031, 81531-990, PR, Curitiba, Brazil.
Hypericum perforatum extract exhibits an antidepressant effect and since several antidepressant drugs are also effective on generalised anxiety disorder (GAD) and panic disorders (PD), H. perforatum may possess some anxiolytic/antipanic effect. Thus, the aim of the present study was to evaluate the putative antipanic/anxiolytic effect of standardised H. perforatum extract (LI 160) on rats tested in the elevated T-maze, an animal model of innate (panic) and learned (generalised) anxiety, at doses that exhibit antidepressant-like activity. H. perforatum (150, 300 and 500 mg/kg, administered orally 24, 18 and 1h before the test) decreased the immobility time in the forced swim test. Rats were treated orally with H. perforatum (150 or 300 mg/kg) or paroxetine (5mg/kg) 24, 18, and 1h before being tested in the elevated T-maze (subacute treatment). Immediately after this test, the animals were submitted to the open field to evaluate locomotor activity. Paroxetine was used as a positive control, since it was clinically effective in GAD and PD. Other groups of animals were submitted to the same drug treatment for 7 days (subchronic treatment). Paroxetine (5mg/kg) impaired inhibitory avoidance after subacute treatment, while subchronic administration increased one-way escape latency. Subacute treatment with H. perforatum (300 mg/kg) exerts a partial anxiolytic-like effect in the inhibitory avoidance task. Repeated administration of H. perforatum (300 mg/kg) induced an anxiolytic effect (decreased inhibitory avoidance) and an antipanic effect (increased one-way escape). No effect on locomotor activity was found with any treatment. Thus, the results suggest that H. perforatum extract could exert an anxiolytic and antipanic effect.
Oncogene. 2002 Feb 14;21(8):1242-50.
Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis.Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, Termeer CC, Gilb B, Kaufmann T, Borner C, Sleeman JP, Simon JC.
Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany. schempp@haut.ukl.uni-freiburg.de
Hyperforin is a plant derived antibiotic from St. John's wort. Here we describe a novel activity of hyperforin, namely its ability to inhibit the growth of tumour cells by induction of apoptosis. Hyperforin inhibited the growth of various human and rat tumour cell lines in vivo, with IC(50) values between 3-15 microM. Treatment of tumour cells with hyperforin resulted in a dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-specific morphological changes. In MT-450 mammary carcinoma cells hyperforin increased the activity of caspase-9 and caspase-3, and hyperforin-mediated apoptosis was blocked by the broad-range caspase inhibitor zVAD.fmk. When added to MT-450 cells, hyperforin, but not paclitaxel, induced a rapid loss of the mitochondrial transmembrane potential Deltapsi(m), and subsequent morphological changes such as homogenization and vacuolization of mitochondria. Monitoring of Deltapsi(m) revealed that the hyperforin-mediated mitochondrial permeability transition can not be prevented by zVAD.fmk. This indicates that mitochondrial permeabilization is a cause rather than a consequence of caspase activation. Moreover, hyperforin was capable of releasing cytochrome c from isolated mitochondria. These findings suggest that hyperforin activates a mitochondria-mediated apoptosis pathway. In vivo, hyperforin inhibited the growth of autologous MT-450 breast carcinoma in immunocompetent Wistar rats to a similar extent as the cytotoxic drug paclitaxel, without any signs of acute toxicity. Owing to the combination of significant antitumour activity, low toxicity in vivo and natural abundance of the compound, hyperforin holds the promise of being an interesting novel antineoplastic agent that deserves further laboratory and in vivo exploration.
Eur J Pharm Biopharm. 2003 Jul;56(1):121-32.
Hyperforin a constituent of St John's wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines.Hostanska K, Reichling J, Bommer S, Weber M, Saller R.
Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland. katarina.hostanska@access.unizh.ch
Hyperforin (HP) is an abundant component of St John's wort with antibiotic and antidepressive activity. We report here the ability of HP and that of polyphenolic procyanidin B2 (PB-2) to inhibit the growth of leukemia K562 and U937 cells, brain glioblastoma cells LN229 and normal human astrocytes. HP inhibited the growth of cells in vitro with GI(50) values between 14.9 and 19.9 microM. The growth inhibitory effect of PB-2 was more pronounced in leukemia cell lines K562 and U937, the GI(50) concentrations being about 12.5 microM established after 48 h incubation differed significantly (P<0.05) from those of LN229 and normal human astrocytes (103.1 and 96.7 microM), respectively. Further, HP and hypericin (HY) (a naphthodianthrone from St John's wort) acted synergistically in their inhibitory effect on leukemic (K562, U937) cell growth. Cell death occurred after 24 h treatment with HP and PB-2 by apoptosis. A dose-dependent loss of membrane phospholipid asymmetry associated with apoptosis was induced in all cell lines as evidenced by the externalization of phosphatidylserine (PS) and morphological changes in cell size and granulosity by scatter characteristics. In leukemia U937 cells, HP increased the activity of caspase-9 and caspase-3 and in K562 cells caspase-8 and caspase-3. In addition, the broad spectrum caspase inhibitor z-VAD-fmk inhibited both the appearance of PS exposure and the activation of caspases, illustrating the functional relevance of caspase activation during HP-induced apoptosis. Cytocidal effects of HP and its cooperation with HY on tumor growth inhibition in a synergistic manner make the St John's wort an interesting option in cancer warranting further in vitro and in vivo investigation.
poster:Larry Hoover
thread:257316
URL: http://www.dr-bob.org/babble/alter/20030903/msgs/257316.html