€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BMJ (CLINICAL RESEARCH ED.)***** Linde K Ramirez G Mulrow CD Pauls A Weidenhammer W Melchart D St John's wort for depression--an overview and meta-analysis of randomised clinical trials [see comments] In: BMJ (1996 Aug 3) 313(7052):253-8 ISSN: 0959-8138 OBJECTIVE--To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. DESIGN--Systematic review and meta-analysis of trials revealed by searches. TRIALS--23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. MAIN OUTCOME MEASURES--A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. RESULTS--Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. CONCLUSION--There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed. Comment in: BMJ 1996 Aug 3;313(7052):241-2 Comment in: BMJ 1996 Nov 9;313(7066):1204-5 Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DISS ABSTR INT [B]***** Thomas-Bradley CJ Hypericin as a potential photosensitizer in photodynamic therapy of cancer. In: Diss Abstr Int [B] (1992) 52(9):4715 ISSN: 0419-4217 The polycyclic aromatic quinone hypericin, which is capable of photoactivation and is biosynthesized by Hypericum plant species, was examined as a potential agent for chemotherapy and for photodynamic therapy of neoplastic disease. The model systems used to test for activity were a mitochondrial succinoxidase enzyme activity assay, an EMT6 mouse mammary carcinoma clonogenic assay, and an MX-1 human mammary carcinoma antitumor assay. Parallel experiments were conducted in the presence and absence of light. Pure hypericin and acetone extracts of Hypericum perforatum were tested for activity and yielded similar results. In the dark, hypericin inhibited succinoxidase activity in isolated mitochondrial membranes, but had no effect on EMT6 cells or MX-1 tumors. However, photoactivated hypericin exhibited activity in all test systems. In particular, photoactivated hypericin inhibited succinoxidase activity at nmol/mg mitochondrial protein levels, EMT6 cell clonogenicity at uM levels, and MX-1 relative tumor wt growth in ip and it dosed animals at 1 mg/kg body wt levels. Experiments designed to elucidate the mechanistic parameters of hypericin's biological activity were also conducted. The results show that photosensitized inhibition of mitochondrial succinoxidase was drug dose-, light dose-, and wavelength-dependent with the greatest inhibition occurring by 600 nm light activation. Hypericin photosensitized singlet oxygen generation was also light dose- and wavelength-dependent. Unequivocal evidence for hypericin photosensitized singlet oxygen generation was obtained using kinetic isotope ratios of products from the reaction between singlet oxygen and the germinally deuterated singlet oxygen trap, tetramethylethylene. The data are consistent with a type II singlet oxygen-mediated mechanisms for hypericin photosensitized succinoxidase inhibition. The photodynamic effect of hypericin on EMT6 cells was examined under hypoxic and aerobic conditions, and photocytotoxicity was found to be oxygen-dependent. The findings suggest that type I oxygen-independent photooxidation reactions do not contribute significantly to hypericin's photodynamic mechanism of action. Fluorescence photomicrographs of hypericin in EMT6 cells show that hypericin is distributed throughout the plasma and cytosolic membranes but is absent from the nucleus, indicating that the events which lead to photocytotoxicity may not involve direct damage to nuclear DNA. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD92-04134). Registry Numbers: 548-04-9 (hypericin) EC 1.- (succinate oxidase) EC 1. (Oxidoreductases) 7782-44-7 (Oxygen) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NATL CONF HUM RETROVIRUSES RELAT INFECT (1ST)***** Mcauliffe V Gulick R Hochster H Liebes L Vaccariello J Hussey S Bassiakos Y Balfour H Stein D Crumpacker C et al A phase I dose escalation study of synthetic hypericin in HIV infected patients (ACTG 150). In: Natl Conf Hum Retroviruses Relat Infect (1st) (1993 Dec 12-16):159 Introduction: Hypericin (HY), an anthracenedione present in Hypericum perforatum (St. John's wort), is active in vitro against HIV. We describe a phase I study of IV dosed synthetic HY. Methods: HIV- infected patients (Pts) with less than or equal to 300 CD4 cells were eligible for enrollment. Pts received IV HY at 0.25 or 0.5 mg/kg BIW or 0.25 mg/kg TIW; with assessments of toxicity, pharmacokinetic (PK) and antiviral activity. 4 Pts received a single oral dose. Results: 25 Pts received HY from 1 to 24 weeks. Phototoxicity (discomfort and erythema of light-exposed areas) developed in all pts, varied in severity, and was dose limiting at 0.5 mg/ kg BIW. PK showed area under the curve of 26.0 +/- 5.0 (Mean +/- SD) and 53.7 +/- 27.2 +/- micrograms/hr/ml at IV doses of 0.25 and 0.5 mg/kg, respectively; peak levels were 4.2 +/- 1.1 and 7.7 +/- 2.0 micrograms/ml and fell below 1 microgram/ml at 5 and 11 hours. Elimination half lives were 23.7 +/- 7.3 and 35.3 +/- 9 hrs (p greater than 0.1). Oral bioavailability was 22.3 +/- 7.7%. A consistent change in antiviral endpoints was not seen with intermittent IV dosing. Conclusions: IV dosing of Hy yields dose-limiting cutaneous phototoxicity of variable severity. PK data predict chronic oral dosing should achieve sustained blood levels in an anti-retroviral range. Further studies of Hypericin are planned. Registry Numbers: 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF CHINESE MEDICINE***** Chen JY Lin CC Namba T Development of natural crude drug resources from Taiwan (X). Pharmacognostical studies on the Chinese crude drug "han-lian-cao". In: Am J Chin Med (1992) 20(1):51-64 ISSN: 0192-415X In a previous paper(1), it was reported that the drug "Han-lian-cao", in Taiwan was derived from the entire plant or aerial part of Eclipta prostrata L. and Alternanthera sessilis R. Brown. In this paper, the histological studies of "Han-lian-cao" derived from Wedelia and Hypericum plants, and of 3 species of Wedelia related plants distributed in Taiwan were made. The results showed that it was possible to classify these species by their external and internal characteristics. In addition, a key to the characteristics of the whole plants of Eclipta, Alternanthera, Wedelia and Hypericum plants are hereby given. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANTICANCER RESEARCH***** Vandenbogaerde A de Witte P Antineoplastic properties of photosensitized hypericin (Meeting abstract). In: Anticancer Res (1995) 15(5A):1757-8 ISSN: 0250-7005 In folk medicine Hypericum perforatum is reported to have antineoplastic properties. In a previous study we have shown that hypericin, the main constituent of Hypricum perforatum, specifically inhibited elements of the mitogenic signal transduction. Subsequently, the in vitro cytotoxic and in vivo antitumoral properties of photosensitized hypericin were investigated. In vitro studies demonstrated a dramatic difference in sensitivity of cell lines towards photo-activated hypericin using a neutral red assay. Using confocal laser microscopy it was shown that the cytotoxicity correlated with the cellular uptake of hypericin. The in vivo antitumoral activity hypericin was tested on A431 cell xenografts in athymic nude mice. A dose-dependent antitumoral effect was observed by intraperitoneal administration of hypericin in light-treated animals; a complete inhibition of the tumor growth was achieved from 50 ug (2.5 mg/kg) hypericin ip administered. The photo-sensitizer accumulated in A431 xenografts after local light irradiation. These results show that the naphthodianthrone hypericin is a potential photochemotherapeutic agent. (2 Refs) Registry Numbers: 548-04-9 (hypericin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANTIMICROBIAL AGENTS AND CHEMOTHERAPY***** Kerb R Brockmoller J Staffeldt B Ploch M Roots I Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. In: Antimicrob Agents Chemother (1996 Sep) 40(9):2087-93 ISSN: 0066-4804 Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St. John's Wort extract LI 160, a plantal antidepressant. Oral administration of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH resulted in median peak levels in plasma (Cmax) of 1.3, 7.2, and 16.6 micrograms/liter for H and 3.4, 12.1, and 29.7 micrograms/liter for PH, respectively. The Cmax and the area under the curve values for the lowest dose were disproportionally lower than those for the higher doses. A lag time of 1.9 h for H was remarkably longer than the 0.4-h lag time for PH. Median half-lives for absorption, distribution, and elimination were 0.6, 6.0, and 43.1 h after 750 micrograms of H and 1.3, 1.4, and 24.8 h after 1,578 micrograms of PH, respectively. Fourteen-day treatment with 250 micrograms of H and 526 micrograms of PH three times a day resulted in median steady- state trough levels of 7.9 micrograms/liter for H and 4.8 micrograms/liter for PH after 7 and 4 days, respectively; the corresponding Cssmax levels were 8.8 and 8.5 micrograms/liter, respectively. Kinetic parameters after intravenous administration of Hypericum extract (115 and 38 micrograms for H and PH, respectively) in two subjects corresponded to those estimated after an oral dosage. Both H and PH were initially distributed into a central volume of 4.2 and 5.0 liter, respectively. The mean distribution volumes at steady state were 19.7 liters for H and 39.3 liters for PH, and the mean total clearance rates were 9.2 ml/min for H and 43.3 ml/min for PH. The systemic availability of H and PH from LI 160 was roughly estimated to be 14 and 21%, respectively. Treatment with Hypericum extract, even in high doses, was well tolerated. Registry Numbers: 198-55-0 (Perylene) 548-04-9 (hypericin) 55954-61-5 (pseudohypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Perovic S Muller WE Pharmacological profile of hypericum extract. Effect on serotonin uptake by postsynaptic receptors. In: Arzneimittelforschung (1995 Nov) 45(11):1145-8 ISSN: 0004-4172 In the present study is is reported that the methanolic Hypericum extract LI 160 (Jarsin 300) exerts no protective effect against N- methyl-D-aspartate (NMDA-) or gp120- (from the HIV virus) induced cytotoxicity. Moreover, it is established that Hypericum extract causes no activation of arachidonic acid release from neurons activated by gp120; hence it displays no sensitization effect on the NMDA receptor channel. The main outcome of this study is the finding that Hypericum extract causes a 50% inhibition (IC50 value) of serotonin uptake by rat synaptosomes at a concentration of 6.2 microglml. Therefore it is concluded that the antidepressant activity of Hypericum extract is due to an inhibition of serotonin uptake by postsynaptic receptors. Future studies might focus on the effect of Hypericum extract on serotonin binding to neurons, serotonin storage in granules, the rate of synthesis of serotonin, and on the activity of monoamine oxidase. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) 506-32-1 (Arachidonic Acid) 6384-92-5 (N-Methylaspartate) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Melzer R Fricke U Holzl J Vasoactive properties of procyanidins from Hypericum perforatum L. in isolated porcine coronary arteries. In: Arzneimittelforschung (1991 May) 41(5):481-3 ISSN: 0004-4172 Procanidin fractions (PC) were isolated from Hypericum perforatum L. (Guttiferae). Characterization of the main components of each fraction was performed by UV- and mass spectroscopy. Their biological activity was tested in porcine isolated coronary arteries. All PC fractions antagonized histamine- or prostaglandin F2 alpha-induced arterial contractions. In contrast, vasorelaxation was insignificant in KCl-precontracted coronary arteries except with the higher oligomeric PC fraction 3. Vasoactive properties of the PC seem to be dependent on their relative molecular mass. An inhibition of cellular phosphodiesterase might be involved in the underlying mechanism of action. Registry Numbers: 154-23-4 (Catechin) 4852-22-6 (procyanidin) 51-45-6 (Histamine) 551-11-1 (Dinoprost) 7447-40-7 (Potassium Chloride) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Okpanyi SN Lidzba H Scholl BC Miltenburger HG [Genotoxicity of a standardized Hypericum extract] Genotoxizitat eines standardisierten Hypericum-Extraktes. In: Arzneimittelforschung (1990 Aug) 40(8):851-5 ISSN: 0004-4172 (Published in German) St. John's wort (Hypercum perforatum) contains hypericin and hypericin-like substances as well as flavonoids, of which particularly Quercetin has generated a wide-spread controversial discussion with respect to mutagenic action. The genotoxicity of a standardized aqueous ethanolic Hypericum extract (Hypericum extract Steigerwald, Psychotonin M) was verified in different in-vivo and in- vitro testsystems with mammalian cells. The in-vitro investigations were performed with the HGPRT (hypoxanthine guanidine phosphoribosyl transferase)-test, UDS (unscheduled DNA synthesis)-test and with the cell transformation test using Syrian hamster embryo cells. Both the in-vitro tests as well as the in-vivo tests--fur spot test of the mouse and the chromosome aberration test with the bone marrow cells of the chinese hamster--were negative, giving completely no indication of a mutagenic potential of Hypericum extract. These investigations lend support to the view that results from bacterial short-term tests are of very limited transferability to human. Registry Numbers: EC 2.4.2.8 (Hypoxanthine Phosphoribosyltransferase) 198-55-0 (Perylene) 548-04-9 (hypericin) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Muldner H Zoller M [Antidepressive effect of a Hypericum extract standardized to an active hypericine complex. Biochemical and clinical studies] Antidepressive Wirkung eines auf den Wirkstoffkomplex Hypercin standardisierten Hypericum-Extraktes. Biochemische und klinische Untersuchungen. In: Arzneimittelforschung (1984) 34(8):918-20 ISSN: 0004-4172 (Published in German) In 6 women with depressive symptoms aged 55-65 years the effect on the excretion of urinary metabolits of noradrenaline and dopamine was measured after a monotherapy with the active hypericine complex (Psychotonin M). In all patients there was a significant increase in 3-methoxy-4-hydroxyphenylglucol which is considered an expression of a beginning antidepressive reaction. With the same patients supplemented with further 9 cases the clinical influence on the depression was measured during a period of 4-6 weeks, with the rating- scales SCAG (Clinical assessment geriatric scale) and DSI (Depression Status Inventory) there was shown a quantitative improvement of the items anxiety, dysphoric mood, loss of interest, hypersomnia, anorexia, depression regularly worse in the morning, insomnia, obstipation, psychomotoric retardation and feeling of worthlessness. Registry Numbers: 198-55-0 (Perylene) 534-82-7 (Methoxyhydroxyphenylglycol) 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Okpanyi SN Weischer ML [Animal experiments on the psychotropic action of a Hypericum extract] Tierexperimentelle Untersuchunger zur psychotropen Wirksamkeit eines Hypericum-Extraktes. In: Arzneimittelforschung (1987 Jan) 37(1):10-3 ISSN: 0004-4172 (Published in German) Extracts of Hypericum perforatum (Psychotonin M) (St. John's wort) with known concentrations of hypericin were tested in several models generally accepted as screening methods in experimental animal studies for the recognition of psychotropic, and in particular of antidepressant activity. Hypericum extract enhanced the exploratory activity of mice in a foreign environment, significantly prolonged the narcotic sleeping time dose-dependently, and within a narrow dose range exhibited reserpine antagonism. Similar to most other antidepressants, hypericum extract enhanced significantly the activity of mice in the water wheel test and after a prolonged daily administration decreased aggressiveness in socially isolated male mice. The presented data in addition to the already proven clinical efficacy justify the use of standardised Hypericum extract in the treatment of mild to moderate depression. Registry Numbers: 4205-90-7 (Clonidine) 50-49-7 (Imipramine) 50-55-5 (Reserpine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS***** Takahashi I Nakanishi S Kobayashi E Nakano H Suzuki K Tamaoki T Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. In: Biochem Biophys Res Commun (1989 Dec 29) 165(3):1207-12 ISSN: 0006-291X Hypericin and pseudohypericin which have been isolated from plants of the Hypericum family are aromatic polycyclic diones. Daniel Meruelo et. al. have reported that hypericin and pseudohypericin showed potent antiretroviral activity including anti-human immunodeficiency virus (1,2). However, the mechanism of these antiretroviral activities has not been clarified. In the course of screening specific inhibitors of protein kinase C we have found that both compounds specifically inhibit protein kinase C with IC50 values 1.7 micrograms/ml and 15 micrograms/ml, respectively, and show antiproliferative activity against mammalian cells. These data suggest that antiretroviral activity of hypericin and pseudohypericin could be attributable to the inhibition of some phosphorylation involved by protein kinase C during viral infection of cells. Registry Numbers: EC 2.7.1.- (Protein Kinase C) EC 2.7.1.117 (Myosin-Light-Chain Kinase) EC 3.4.22.17 (Calpain) 198-55-0 (Perylene) 548-04-9 (hypericin) 55954-61-5 (pseudohypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOFIZIKA***** Bol'shakova IV Lozovskaia EL Sapezhinskii II [Antioxidant properties of a series of extracts from medicinal plants] Antioksidantnye svoistva riada ekstraktov lekarstvennykh rastenii. In: Biofizika (1997 Mar-Apr) 42(2):480-3 ISSN: 0006-3029 (Published in Russian) Investigation of antioxidant properties of some plants was carried out. A group of plants affected human central nervous system was studied in detail. Efficiency of plants as antioxidants was tested by the influence of their extracts on the yield of photochemiluminescence of Gly-Trp solutions. Antioxidant properties were examined under conditions when their own absorption was minimized. Riboflavin as additional sensitizer was used in this experiment for superoxide generation. The antioxidant effect was evaluated with regard to single dose of plant extracts and their concentration in human organism. The effect decreases in the following consequence: Hypericum > Eleutherococcus > Rhodiola > Leonurus > Aralia > Valeriana > Echinopanax > Schizandra > Panax gin- seng. Registry Numbers: 83-88-5 (Riboflavin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EKSPERIMENTALNAIA I KLINICHESKAIA FARMAKOLOGIIA***** Evstifeeva TA Sibiriak SV [The immunotropic properties of biologically active products obtained from Klamath weed (Hypericum perforatum L.)] Immunotropnye svoistva biologicheski aktivnykh produktov, poluchennykh iz zveroboia prodyriavlennogo. In: Eksp Klin Farmakol (1996 Jan-Feb) 59(1):51-4 ISSN: 0869-2092 (Published in Russian) We carried out a systematic study of immunotropic activity of John's wort on the level of integrated fractions including all basic active substances of this plant. Both types of substances capable of increasing and suppressing the immunity were found in John's wort. Polyphenol fraction exhibits the immunostimulating activity with respect to the system of mononuclear phagocyte system, cellular and humoral immunity, and is capable of recovering the immune response in conditions of high-zone tolerance. Lipophilic fraction of this plant exhibits immunosuppressing properties with respect to cellular and humoral immune response. Immunotropic activity of polyphenol and lipophilic fractions correlate with their low toxicity. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FORTSCHRITTE DER MEDIZIN***** Witte B Harrer G Kaptan T Podzuweit H Schmidt U [Treatment of depressive symptoms with a high concentration hypericum preparation. A multicenter placebo-controlled double-blind study] Behandlung depressiver Verstimmungen mit einem hochkonzentrierten Hypericumpraparat. In: Fortschr Med (1995 Oct 10) 113(28):404-8 ISSN: 0015-8178 (Published in German) In a multicenter, placebo-controlled double-blind trial, the effect on depression (ICD 10 F 32.1) of treatment with an innovative highly concentrated hypericum preparation was investigated. The study contained 97 outpatients who received 100 to 120 mg of the hypericum extract bid. The course of the illness was assessed with the Hamilton Depression Scale (HAMD), the von Zerssen Depressivity Scale (D-S) and the Clinical Global Impression Scale (CGIS). Treatment resulted in an appreciable improvement in the symptoms of depression, and the 70% response rate (n = 43), corresponded to that of chemical antidepressants. The preparation also showed an anxiolytic effect. The substance was extremely well tolerated, and no side-effects were reported by any of the patients. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Ernst E [St. John's wort as antidepressive therapy] Johanniskraut zur antidepressiven Therapie. In: Fortschr Med (1995 Sep 10) 113(25):354-5 ISSN: 0015-8178 (Published in German) St. John's Wort (Hypericum perforatum) has been used to treat a variety of complaints since ancient times. Recent studies have shown that it is clinically effective for the treatment of the symptoms of depression. It has proved superior to placebo, equally as effective as standard medication and has a clear advantage over the latter in terms of side-effects. It follows that, on the basis of our present knowledge, St. John's Wort can be recommended for use as an anti- depressant. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Schmidt U Sommer H [St. John's wort extract in the ambulatory therapy of depression. Attention and reaction ability are preserved] Johanniskraut-Extrakt zur ambulanten Therapie der Depression. Aufmerksamkeit und Reaktionsvermogen bleiben erhalten. In: Fortschr Med (1993 Jul 10) 111(19):339-42 ISSN: 0015-8178 (Published in German) METHOD: In a placebo-controlled, randomized, double-blind trial involving outpatients with mild to moderately severe depression, an extract of St. John's wort (Hypericum), LI 160, a herbal antidepressant was tested for efficacy and tolerability, as well as for possible negative effects on cognitive performance. RESULTS: The responder rate to treatment with the extract was 66.6% as compared with only 26.7% with placebo. The treatment was very well tolerated; only in two patients did transient minor side effects occur under LI 160. No impairment of cognitive performance was observed: during the trial, Hypericum did not lead to any impairment of attention, concentration or reaction. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL CONFERENCE ON AIDS***** Vonsover A Steinbeck KA Rudich C Mazur Y Lavie D Mandel M Lavie G HIV-1 virus load in the serum of AIDS patients undergoing long term therapy with hypericin. In: Int Conf AIDS (1996 Jul 7-12) 11(1):120 (abstract no. Mo.B.1377) Objectives: Assessment of the antiretroviral efficacy of long term therapy with plant derived hypericin on p24 antigen and on viral load in AIDS patients. Methods: Eighteen Seropositive symptomatic individuals received monotherapy with plant derived hypericin [i.v. 1x2 ml weekly plus 6x2 hypericum perforatum tablets (Jossa) per day] for periods ranging between 48-72 months. Plasma viral RNA loads were monitored using Nucleic Acid Amplification Assay (NASBA, Organon- Teknika), and p24 antigen with an HIV-1 Antigen Base Dissociation Assay (Organon-Teknika); they were followed during 40 months of therapy. Results: We have previously identified hypercin as a broad spectrum virucidal agent, whose mechanism of action is unlikely to be affected by development of drug-resistant virus strains. Resistant strains hamper the efficacy of all antivirals developed thus far. Hypericin is a lipophilic compound that binds the virus membrane of lipid coated viruses. This photodynamic molecule absorbs a photon of energy, generates excited oxygen species that covalently cross-link the viral capsid proteins and prevent virus uncoating during infection. We have evaluated the antiretroviral properties of hypericin in 18 AIDS patients treated with the agent for 4-6 years. Among the 18 participants, 33% had measurable, pretreatment concentrations of serum p24 antigen, one became positive after 24 months and twelve remained p24 antigen negative throughout the follow- up period. Four patients exhibited significant long term declines in p24 antigen levels; the levels remained unchanged in 2 others. HIV-1 RNA was detected in 83% of the patients with a mean of maximal RNA load of 5.33 and 5.00 log10 copies/ml in p24 antigen-positive or negative patients respectively. A substantial decline in viral load (from 5.0 to 4.23 log10 copies/ml) was observed in most of the p24 Ag. positive and negative individuals. In some patients an increase in virus load was observed throughout a three year treatment period without effect on the clinical conditions of viral CMV, herpes or EBV complications being encountered. Conclusions: These findings provide strong support to the use of hypericin or its plant-derived form (Hypericum perforatum) as non-toxic and effective long term antiviral treatment modalities. More extended trials with more patients of all CDC categories are in progress. Registry Numbers: 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Steinbeck-Klose A Wernet P Successful long term treatment over 40 months of HIV-patients with intravenous Hypericin. In: Int Conf AIDS (1993 Jun 6-11) 9(1):470 (abstract no. PO-B26-2012) In an open pilot study 18 HIV patients (3 with the CDC II, 8 with CDC III, 4 with CDC IV B and 3 with CDC IV C1 classification) were treated solely with Hyperforat (Klein), i.v. 2x2 mL weekly plus 3x2 Hypericum tablets (Jossa) per day. The 16/18 patients with good study compliance in their majority showed stable or even increasing counts of absolute CD4 values for helper T cells over the 40 months of observation until now. It is remarkable that this trend was apparently not dependent on the level of the absolute CD4 count at the beginning of the Hypericum treatment. Also the CD4/CD8 ratio showed an improvement in the majority of these patients. Clinically, it was noteworthy that only two of these 16 patients encountered an opportunistic infection during the 40 months of observation. The other 14/16 patients remained clinically stable and are active in work and life with a Karnovsky-Index of 100. This steady state situation of the HIV infection also correlated with stable values of hemoglobin, leukocytes and platelets. Furthermore, none of the otherwise known viral complications due to CMV, herpes or EBV was encountered in these 16 patients. Also in no instance a toxoplasmosis nor neurological symptoms became apparent. Hypericum perforatum is presented as a novel effective anti-viral substance of broader activity, though with an hitherto unknown mode of action. It should be noted that no side effects have been seen or measured in any of these 16 patients until now. On this basis an extended trial with more patients in all CDC categories seems warranted now. Registry Numbers: 198-55-0 (Perylene) 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CHROMATOGRAPHY***** Decosterd LA Dorsaz AC Hostettmann K Application of semi-preparative high-performance liquid chromatography to difficult natural product separations. In: J Chromatogr (1987 Oct 2) 406:367-73 ISSN: 0021-9673 Semi-preparative high-performance liquid chromatography on RP-18 with methanol-water as the mobile phase was used for the separation of homologous antifungal chromenes and related homologous dichromenes from Hypericum revolutum Vahl (Guttiferae). In the course of the structural elucidation of new saponins from Phylolacca dodecandra L'Herit. (Phytolaccaceae), two isomeric oleanane saponins were separated on RP-8 with acetonitrile-water as the mobile phase. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Rivera D Obon C The ethnopharmacology of Madeira and Porto Santo Islands, a review. In: J Ethnopharmacol (1995 May) 46(2):73-93 ISSN: 0378-8741 The ethnopharmacology of Madeira and Porto Santo Islands is extremely interesting because of the cultural and biogeographic features of this region, which make it a centre of medicinal plant diversity (richness of endemic flora, geographical isolation in the Atlantic sea, crosscultural influences, and past abundance of local healers). The medicinal flora of Madeira is composed of 259 species. Some noteworthy medicinal taxa, endemic or locally relevant, are: Acanthus mollis, Aeonium glandulosum, Aeonium glutinosum, Bidens pilosa, Borago officinalis, Chamaemelum nobile var. discoideum, Culcita macrocarpa, Echium nervosum, Euphorbia platiphylla, Helichrysum melaleucum, Helichrysum obconicum, Hypericum glandulosum, Hypericum humifussum, Kleinia repens, Laurus azorica, Monizia edulis, Ocotea foetens, Psoralea bituminosa, Rubus bollei, Rumex maderensis, Sambucus lanceolata, Scilla maderensis, Sedum brissemoretii, Sedum farinosum, Sedum nudum, Sibthorpia peregrina, Teucrium betonicum, Thymus caespititius, Trifolium squamosum and Vaccinium padifolium. Among the medicinal cryptogams, one can underline the parasitic fungus Laurobasidium lauri, which grows on the stems of Laurus azorica and is used as an antirheumatic, haemostatic, emmenagogue, insecticide and analeptic. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Taylor RS Manandhar NP Hudson JB Towers GH Antiviral activities of Nepalese medicinal plants. In: J Ethnopharmacol (1996 Jul 5) 52(3):157-63 ISSN: 0378-8741 In a screening of plants used traditionally in Nepal to treat diseases that could be caused by viruses, methanol extracts from 21 species were assayed for activity against three mammalian viruses: herpes simplex virus, Sindbis virus and poliovirus. Assays were performed in UV-A or visible light, as well as dark. Individual species of Hypericum, Lygodium, and Maesa exhibited impressive antiviral activities, although their selective effects on the three viruses suggested that the antiviral ingredients were different in each extract. In addition, many of the other extracts showed partial inactivation of one or more test viruses. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Tammaro F Xepapadakis G Plants used in phytotherapy, cosmetics and dyeing in the Pramanda district (Epirus, North-West Greece). In: J Ethnopharmacol (1986 Jun) 16(2-3):167-74 ISSN: 0378-8741 Thirty plants used in phytotherapy, cosmetics and dyeing in the Pramanda district (North-West Greece) are reported. For many plants (myrtle, phlomis, daphne, etc.) the uses are localized and not noted for other phytotherapies; some uses coincide with those existing in other zones of the Mediterranean (mint, thyme, red juniper, Hypericum, etc.). The plants used are the most common and most easily found in this area. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY***** Sommer H Harrer G Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S9-11 ISSN: 0891-9887 One hundred and five outpatients with mild depressions of short duration were treated in a double-blind study with either 3 x 300 mg hypericum extract or placebo. The therapy phase was 4 weeks. The effectiveness was judged according to the Hamilton Depression Scale after 2 and 4 weeks. The values of the mean basic score in these periods fell from 15.8 to 9.6 or 7.2 in the active group, and in the placebo group, from 15.8 to 12.3 and 11.3. The differences between active and placebo groups were statistically significant with P < .05 and P < .01 achieved after 2 and 4 weeks, respectively. In the active group, 28 of 42 patients (67%) and, in the placebo group, 13 of 47 patients (28%) responded to treatment. Notable side effects were not found. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wagner H Bladt S Pharmaceutical quality of hypericum extracts. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S65-8 ISSN: 0891-9887 Hypericum extracts contain at least ten constituents or groups of components that may contribute to the pharmacological effects. It is not yet possible to correlate the antidepressive mode of action with specific constituents; therefore, the pharmaceutical quality of the extracts was characterized on the basis of typical leading substances and especially the hypericins. For the analysis and improvement of the production procedure, the content of hypericin and pseudohypericin was measured experimentally. The drug material was extracted with different solvents and the yield was analyzed for each kind of solvent, its concentration and extraction temperature. Optimal yields were obtained with 80% methanol at temperatures of 80 degrees C. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) 548-04-9 (hypericin) 55954-61-5 (pseudohypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Muller WE Rossol R Effects of hypericum extract on the expression of serotonin receptors. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S63-4 ISSN: 0891-9887 The influence of hypericum extract LI 160 on the expression of serotonin receptors was investigated using a neuroblastoma cell line to establish a model for the regulation of neurotransmitters by immunologically active compounds such as cytokines. The cells were incubated with hypericum extract LI 160 in kinetic form for 2, 4, 6, 8, and 10 hours, then washed. The serotonin receptor expression analysis was compared to that of a placebo control solution. The neuroblastoma cells showed a clearly reduced expression of the serotonin receptors under treatment with hypericum extract. First stimulation experiments with interleukin-1 (IL-1) and hypericum extract suggest that a further reduction of the serotonin receptors is possible when IL-1 is added. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Thiele B Brink I Ploch M Modulation of cytokine expression by hypericum extract. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S60-2 ISSN: 0891-9887 The effect of hypericum extract LI 160 on the stimulated cytokine expression was investigated in vitro in a whole blood culture system. Blood samples were taken from five healthy volunteers and four depressive patients. The release of interleukin-6 (IL-6), interleukin- 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) was measured quantitatively after an incubation time of 24 hours on microtiter plates. A massive suppression of the interleukin-6 release was found for PHA-stimulated hypericum extract. Possible relations to the antidepressive effects of hypericum extract are discussed. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Harrer G Schulz V Clinical investigation of the antidepressant effectiveness of hypericum. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S6-8 ISSN: 0891-9887 To date, 25 controlled therapy studies have investigated the antidepressive effectiveness of hypericum extracts. A total of 1592 treatment cases have been included. The dosage was typically 300 to 900 mg total extract daily; the therapy duration was 2 to 6 weeks. Fifteen studies were performed comparing hypericum extracts with placebo, 10 studies as comparative studies. This paper presents an overview of their results. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bladt S Wagner H Inhibition of MAO by fractions and constituents of hypericum extract. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S57-9 ISSN: 0891-9887 The inhibition of monoamine oxidase (MAO) by six fractions from hypericum extract and three characteristic constituents (as pure substances) were analyzed in vitro and ex vivo to study the antidepressive mechanism of action. Rat brain homogenates were used as the in vitro model, while the ex vivo analysis was performed after intraperitoneal application of the test substances to albino rats. Massive inhibition of MAO-A could be shown with the total extract and all fractions only at the concentration of 10(-3) mol/L. At 10(-4) mol/L, one fraction rich in flavonoides showed an inhibition of 39%, and all other fractions demonstrated less than 25% inhibition. Using pure hypericin as well as in all ex vivo experiments, no relevant inhibiting effects could be shown. From the results it can be concluded that the clinically proven antidepressive effect of hypericum extract cannot be explained in terms of MAO inhibition. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Thiede HM Walper A Inhibition of MAO and COMT by hypericum extracts and hypericin. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S54-6 ISSN: 0891-9887 The influence of hypericin, hypericum total extract, and hypericum fractions on the activity of MAO and COMT, prepared in vitro from pork liver, were investigated in several concentration steps. An inhibition of MAO could be shown in the following concentrations (extract correlated to a mean molecular value of 500): hypericin to 10(-3) mol/L, hypericum total extract to 10(-4) mol/L, one extract fraction up to 10(-5). A COMT inhibition could not be shown for hypericin, with hypericum extract to 10(-4) mol/L and with two extract fractions also up to 10(-4) mol/L. The MAO inhibiting fraction contained hypericins as well as flavonols, the COMT- inhibition fraction being mainly flavonols and xanthones. The concentrations of inhibition shown might not be sufficient to explain the clinically proven antidepressive effect of hypericum particularly with regard to the inhibition of MAO activity. Registry Numbers: EC 2.1.1.6 (Catechol Methyltransferase) 117-39-5 (Quercetin) 198-55-0 (Perylene) 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Staffeldt B Kerb R Brockmoller J Ploch M Roots I Pharmacokinetics of hypericin and pseudohypericin after oral intake of the hypericum perforatum extract LI 160 in healthy volunteers. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S47-53 ISSN: 0891-9887 The single- and multiple-dose pharmacokinetics of the naphthodianthrones hypericin and pseudohypericin derived from St. John's wort (Hypericum perforatum, LI 160, Lichtwer Pharma GmbH, Berlin) were studied in 12 healthy male subjects. After a single oral dose of 300, 900, or 1800 mg of dried hypericum extract (250, 750, or 1500 micrograms hypericin and 526, 1578, or 3156 micrograms pseudohypericin), plasma levels were measured with a modified highly sensitive high-pressure liquid chromatography (HPLC) method (lower detection limit 0.1 ng/mL) up to 3 days. The median maximal plasma levels were 1.5, 4.1, and 14.2 ng/mL for hypericin and 2.7, 11.7, and 30.6 ng/mL for pseudohypericin, respectively, for the three doses given above (interim evaluation of four volunteers). The median elimination half-life times of hypericin were 24.8 to 26.5 hours, and varied for pseudohypericin from 16.3 to 36.0 hours. Ranging between 2.0 to 2.6 hours, the median lag-time of absorption was remarkably prolonged for hypericin when compared to pseudohypericin (0.3 to 1.1 hours). The areas under the curves (AUC) showed a nonlinear increase with raising dose; this effect was statistically significant for hypericin. During long-term dosing (3 x 300 mg/day), a steady-state was reached after 4 days. Mean maximal plasma level during the steady- state treatment was 8.5 ng/mL for hypericin and 5.8 ng/mL for pseudohypericin, while mean trough levels were 5.3 ng/mL for hypericin and 3.7 ng/mL for pseudohypericin. In spite of their structural similarities there are substantial pharmacokinetic differences between hypericin and pseudohypericin. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) 548-04-9 (hypericin) 55954-61-5 (pseudohypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Johnson D Ksciuk H Woelk H Sauerwein-Giese E Frauendorf A Effects of hypericum extract LI 160 compared with maprotiline on resting EEG and evoked potentials in 24 volunteers. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S44-6 ISSN: 0891-9887 In a randomized double-blind study, the effect of hypericum extract was compared to that of maprotiline in 24 healthy volunteers. The investigations included measurements of resting EEG as well as visual and acoustic evoked potentials. In resting EEGs, both medications revealed oppositely directed changes in the theta frequencies, and mainly similarly directed changes in alpha and beta frequencies. Measurements of evoked potentials in the theta and beta frequencies supported these results. The results indicate improved cognitive functions mainly with the treatment of hypericum extract. Registry Numbers: 10262-69-8 (Maprotiline) 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Schulz H Jobert M Effects of hypericum extract on the sleep EEG in older volunteers. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S39-43 ISSN: 0891-9887 The effects of treatment with high doses (300 mg three times daily) of hypericum extract LI 160 on sleep quality and well-being were investigated over a 4-week period. The double-blind, placebo- controlled study was conducted with 12 older, healthy volunteers in a cross-over design, which included a 2-week wash-out phase between both treatment phases. A hypostatic influence of the REM sleep phases, which is typical for tricyclic antidepressants and MAO inhibitors, could not be shown for this phytopharmacon. Instead, LI 160 induced an increase of deep sleep during the total sleeping period. This could be shown consistently in the visual analysis of the sleeping phases 3 and 4, as well as in the automatic analysis of slow-wave EEG activities. The continuity of sleep was not improved by LI 160; this was also the case for the onset of the sleep, the intermittent wake-up phases, and total sleep duration. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Woelk H Burkard G Grunwald J Benefits and risks of the hypericum extract LI 160: drug monitoring study with 3250 patients. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S34-8 ISSN: 0891-9887 Effectiveness and acceptance of a 4-week treatment with hypericum extract LI 160 were investigated by 663 private practitioners. The results of the 3250 patients (76% women and 24% men), were recorded using data sheets. The age of the patients ranged from 20 to 90 years (mean 51 years). Of the patients, 49% were mildly depressed, 46% intermediate, and 3% severely depressed. In about 30% of the patients, the situation normalized or improved during the therapy. Undesired drug effects were reported in 79 (2.4%) patients and 48 (1.5%) discontinued the therapy. Most frequently noted side effects were gastrointestinal irritations (0.6%), allergic reactions (0.5%), tiredness (0.4%), and restlessness (0.3%). Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Payk TR Treatment of depression. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S3-5 ISSN: 0891-9887 Depressions are the most common psychiatric diseases. For treatment, plant extracts have been used for thousands of years: examples are extracts from the (sleeping) poppy (opium), deadly nightshade (Atropa belladonna), Indian hemp (hashish), henbane (hyoscyamine), thorn apple (scopolamine), and St. John's wort (hypericum oil). In addition, psychotherapeutic measures, like playing music, dancing, playing theatre, and also the temple sleep, were used. In the 19th century, the introduction of brome (1826), codeine (1832), chloral hydrate (1869), and paraldehyde (1882), as well as the barbiturates (at the turn of the century) introduced significant improvements in pharmacotherapy. The modern thymoleptica therapy started in 1957 with the introduction of imipramine. Now about 40 active antidepressants are marketed. New drug developments should be characterized mainly by an improvement in tolerance. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Martinez B Kasper S Ruhrmann S Moller HJ Hypericum in the treatment of seasonal affective disorders. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S29-33 ISSN: 0891-9887 Seasonal affective disorder (SAD) represents a subgroup of major depression with a regular occurrence of symptoms in autumn/winter and full remission in spring/summer. Light therapy (LT) has become the standard treatment of this type of depression. Apart from this, pharmacotherapy with antidepressants also seems to provide an improvement of SAD symptoms. The aim of this controlled, single-blind study was to evaluate if hypericum, a plant extract, could be beneficial in treating SAD patients and whether the combination with LT would be additionally advantageous. Patients who fulfilled DSM-III- R criteria for major depression with seasonal pattern were randomized in a 4-week treatment study with 900 mg of hypericum per day combined with either bright (3000 lux, n = 10) or dim (< 300 lux, n = 10) light condition. Light therapy was applied for 2 hours daily. We found a significant (MANOVA, P < .001) reduction of the Hamilton Depression Scale score in both groups but no significant difference between the two groups. Our data suggest that pharmacologic treatment with hypericum may be an efficient therapy in patients with seasonal affective disorder. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Harrer G Hubner WD Podzuweit H Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S24-8 ISSN: 0891-9887 A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints. Registry Numbers: 10262-69-8 (Maprotiline) 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Vorbach EU Hubner WD Arnoldt KH Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double-blind study with 135 outpatients. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S19-23 ISSN: 0891-9887 In a double-blind comparative study, 135 depressed patients were treated in 20 centers. Inclusion diagnoses were typical depressions with single episode (296.2), several episodes (296.3), depressive neurosis (300.4), and adjustment disorder with depressed mood (309.0) in accordance with DSM-III-R. The dosage was 3 x 300 mg hypericum extract LI 160 or 3 x 25 mg imipramine daily. The treatment lasted for 6 weeks. Main assessment criteria were the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S) and the Clinical Global Impressions (CGI). In both treatment groups, a parallel reduction of the Hamilton score from 20.2 to 8.8 (LI 160, n = 67) or from 19.4 to 10.7 (imipramine, n = 68), and the transformed D-S point values from 39.6 to 27.2 (LI 160) and 39.0 to 29.2 (imipramine) were found. The analysis of CGI revealed comparable results in both treatment groups. Clinically relevant changes of the safety parameters were not found. In the LI 160 group fewer and milder side effects were found as compared to imipramine. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) 50-49-7 (Imipramine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hansgen KD Vesper J Ploch M Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S15-8 ISSN: 0891-9887 Seventy-two depressive patients of 11 physicians' practices were treated in a double-blind study for a period of 6 weeks either with hypericum extract LI 160 or with placebo. Inclusion criterion was a major depression in accordance with DSM-III-R. The changes were assessed using four psychometric scales (HAMD, D-S, BEB, CGI). After 4 weeks of therapy, the statistical evaluation revealed a significant improvement in all four psychometric tests in the active group as compared to the placebo group. After switching the placebo group to active treatment (5th to 6th week of therapy), significant improvements were found in the original placebo group. No serious side effects were observed. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hubner WD Lande S Podzuweit H Hypericum treatment of mild depressions with somatic symptoms. In: J Geriatr Psychiatry Neurol (1994 Oct) 7 Suppl 1:S12-4 ISSN: 0891-9887 In a randomized, placebo-controlled, double-blind study, 39 patients with depression with somatic symptoms were treated with hypericum extract LI 160. The therapy lasted for 4 weeks; the dosage was 300 mg three times daily. At the onset of the study as well as after 2 and 4 weeks, the following criteria were analyzed: HAMD, B-L, CGI, and vegetative symptoms. The results show a significant improvement in the active treatment group at the 5% level as compared to placebo. Seventy percent of the patients treated with LI 160 were free of symptoms after 4 weeks. Typical symptoms of the depression such as lack of activity, tiredness, fatigue, and disturbed sleep, were especially responsive. In no case were any undesirable side effects observed. Registry Numbers: 117-39-5 (Quercetin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF MEDICINAL CHEMISTRY***** Tada M Chiba K Takakuwa T Kojima E Analogues of natural phloroglucinols as antagonists against both thromboxane A2 and leukotriene D4. In: J Med Chem (1992 Apr 3) 35(7):1209-12 ISSN: 0022-2623 Antagonists against both thromboxane A2 and leukotriene D4 were prepared from phloroglucinol. These compounds showed almost the same activity as the chinesins which were isolated from Hypericum chinese L. The correlation between the structures and activity was studied in the synthesized and naturally occurring phloroglucinol derivatives. Registry Numbers: 108-73-6 (Phloroglucinol) 57576-52-0 (Thromboxane A2) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF NATURAL PRODUCTS***** Jayasuriya H Clark AM McChesney JD New antimicrobial filicinic acid derivatives from Hypericum drummondii. In: J Nat Prod (1991 Sep-Oct) 54(5):1314-20 ISSN: 0163-3864 Bioactivity-guided fractionation of the hexane extract of the stems and leaves of Hypericum drummondii has afforded four new filicinic acid derivatives: drummondin D, isodrummondin D, drummondin E, and drummondin F. The structures of these compounds were established by spectroscopic methods. All compounds possessed strong antibiotic activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and the acid fast bacterium Mycobacterium smegmatis. Registry Numbers: 122127-73-5 (drummondin F) 138169-52-5 (drummondin D) 138169-53-6 (isodrummondin D) 138169-54-7 (drummondin E) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Jayasuriya H McChesney JD Swanson SM Pezzuto JM Antimicrobial and cytotoxic activity of rottlerin-type compounds from Hypericum drummondii. In: J Nat Prod (1989 Mar-Apr) 52(2):325-31 ISSN: 0163-3864 Hexane extracts of Hypericum drummondii showed significant activity against the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and the acid-fast bacterium Mycobacterium smegmatis in an agar well diffusion assay. Employing bioassay-directed fractionation procedures, four new rottlerin-type compounds (drummondins A, B, C[1- 3], and F [4]) were isolated and identified by spectral and physical characterization. The antimicrobial activity of these compounds was comparable to or greater than that demonstrated by streptomycin and generally correlated with cytotoxic activity determined with cultured P-388, KB, or human cancer cell lines (breast, colon, lung, melanoma). No cell-type selectivity was observed. In addition, two known compounds, albaspidins A-A [5] and P-P [6], were isolated and structured characterized. Neither demonstrated appreciable antimicrobial or cytotoxic activity. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF TRADITIONAL CHINESE MEDICINE***** Zheng MS An experimental study of the anti-HSV-II action of 500 herbal drugs. In: J Tradit Chin Med (1989 Jun) 9(2):113-6 ISSN: 0254-6272 Experimental assessments were made on the anti-HSV-II action of 500 herbs by determinations of the virus inhibition logarithm (VIL). 13 highly effective herbs (VIL greater than or equal to 4.00) were screened cut, providing a rational basis for clinical therapy. Among these effective herbs, 10 were aqueous extracts of Artemisia anomala, Centella asiatica, Epimedium Sagittatum, Hibiscus mutabilis, Hosta plantaginea, Hypericum japonicum, Inula japonica, Mosla punctata, Rhododendron simsii, and Rhus chinenses, while 3 were alcohol extracts of Epimedium Sagittatum, Hypericum japonicum, and Mosla punctata. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****LIKARSKA SPRAVA***** Krylov AA Ibatov AN [The use of an infusion of St.-John's-wort in the combined treatment of alcoholics with peptic ulcer and chronic gastritis] Primenenie nastoia travy zveroboia v kompleksnom lechenii bol'nykh alkogolizmom v sochetanii s iazvennoi bolezn'iu i khronicheskim gastritom. In: Lik Sprava (1993 Feb-Mar)(2-3):146-8 ISSN: 1019-5297 (Published in Russian) Hypericum herbal infusion was used in combination with rational psychotherapy of depressive manifestations in 57 outpatients with alcoholism and concomitant diseases of digestive organs. Duration of treatment--2 months (1 glass 4-5 times daily). It is concluded that this treatment in combination with rational psychotherapy proved effective. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NAUCHNYE DOKLADY VYSSHEI SHKOLY. BIOLOGICHESKIE NAUKI***** Smyshliaeva AV Nguyen LH Kudriashov IuB [The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 2.] Modifikatsiia luchevogo porazheniia zhivotnykh vodnym ekstraktom Hypericum perforatum L. Soobshchenie 2. In: Biol Nauki (1992)(4):9-13 ISSN: 0470-4606 (Published in Russian) The preparation Hypericum perforatum L. has been shown to decrease the intensity level of enzymatic and non-enzymatic processes of lipid peroxidation of rat liver microsomes in vitro and in vivo. In the mucus of the this intestine in vivo the increase of the number of non- enzymatic SH-groups is observed. Possible mechanisms of radioprotective action of the preparation is under discussion. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Smyshliaeva AV Kudriashov IuB [The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 1.] Modifikatsiia luchevogo porazheniia zhivotnykh vodnym ekstraktom Hypericum perforatum L. Soobshchenie 1. In: Biol Nauki (1992)(4):7-9 ISSN: 0470-4606 (Published in Russian) The preparation of Hypericum perforatum L. has been shown to possess radioprotective properties. The effect found depends on the time of its taking and its concentration. A statistically reliable protection of marrow and the mucus of the thin intestine of mice from X-rays is observed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACEUTICAL RESEARCH***** Jayasuriya H Baker JK Clark AM McChesney JD Synthesis and the biological evaluation of the structural units of drummondin C. In: Pharm Res (1991 Nov) 8(11):1372-6 ISSN: 0724-8741 Drummondin C (1) is an antibiotic isolated from a bioassay-directed fractionation of Hypericum drummondii (Grev. & Hook.)T.&G. It showed significant activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and the acid-fast bacterium Mycobacterium smegmatis. Two structural units of drummondin C, the 8-acetyl-5,7-dihydroxy-2,2-dimethylchromene (6) and 5-acetyl-3- methyl-filicinic acid (9), were synthesized to determine the relative importance of the two substructure portions to the antibiotic activity of the compound. The low antimicrobial activity of 6 and 9 demonstrates the necessity of both units for the antibiotic activity of drummondin C. Registry Numbers: 119171-78-7 (drummondin C) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHYTOCHEMISTRY***** Rath G Potterat O Mavi S Hostettmann K Xanthones from Hypericum roeperanum. In: Phytochemistry (1996 Sep) 43(2):513-20 ISSN: 0031-9422 Four new xanthones have been isolated from the roots of Hypericum roeperanum. Their structures have been established by a combination of spectroscopic and chemical methods as 1,6-dihydroxy-5-methoxy- 4',5'-dihydro-4',4',5'-trimethylfurano- (2',3':3,4)-xanthone (5-O- methyl-2-deprenylrheediaxanthone B), 1,6-dihydroxy-5-methoxy-6',6'- dimethylpyrano-(2',3':3,4)-xanthone (5-O-methylisojacareubin), 1,3,5,6-tetrahydroxy-2-(2',2'-dimethyl-4'-isopropenyl)-cyclopen tanylxanthone (5-O-demethylpaxanthonin) and 1,3,5,6-tetrahydroxy-4- trans-sesquilavandulylxanthone (roeperanone). In addition, 2- hydroxyxanthone, 5-hydroxy-2-methoxyxanthone, 1,5-dihydroxy-2- methoxyxanthone, 2-deprenyl rheediaxanthone B, isojacareubin and calycinoxanthone D have been isolated and characterized. Some of the isolated xanthones exhibited antifungal activity against Candida albicans. Registry Numbers: 90-47-1 (xanthone) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Rocha L Marston A Kaplan MA Stoeckli-Evans H Thull U Testa B Hostettmann K An antifungal gamma-pyrone and xanthones with monoamine oxidase inhibitory activity from Hypericum brasiliense. In: Phytochemistry (1994 Aug) 36(6):1381-5 ISSN: 0031-9422 A new gamma-pyrone (hyperbrasilone), three known xanthones (1,5- dihydroxyxanthone, 5-hydroxy-1-methoxyxanthone and 6-deoxyjacareubin) and betulinic acid have been isolated from a dichloromethane extract of stems and roots of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, EI-MS, 1H and 13C NMR) and that of the gamma-pyrone was confirmed by X-ray crystallography. Hyperbrasilone and the xanthones were all antifungal against Cladosporium cucumerinum, while the three xanthones showed differing degrees of inhibition of monoamine oxidase A and B. Registry Numbers: 158991-19-6 (hyperbrasilone) 90-47-1 (xanthone) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Rocha L Marston A Potterat O Kaplan MA Stoeckli-Evans H Hostettmann K Antibacterial phloroglucinols and flavonoids from Hypericum brasiliense. In: Phytochemistry (1995 Nov) 40(5):1447-52 ISSN: 0031-9422 Three known phloroglucinols (japonicine A, uliginosin A and isouliginosin B) and a new phloroglucinol (hyperbrasiol A) have been isolated from a petrol extract of the leaves and flowers of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, DCI-MS, 1H and 13CNMR, including SINEPT, HMBC, HSQC, DQFCOSY experiments). The substitution pattern of hyperbrasilol A was confirmed by X-ray crystallography. All four phloroglucinols were antibacterial against Bacillus subtilis in a TLC bioautographic assay. The flavonoids, kaempferol, luteolin, quercetin, quercitrin, isoquercitrin, hyperoside and guaijaverin, were isolated from a methanol extract of the same organs. Registry Numbers: 108-73-6 (Phloroglucinol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Decosterd LA Hoffmann E Kyburz R Bray D Hostettmann K A new phloroglucinol derivative from Hypericum calycinum with antifungal and in vitro antimalarial activity. In: Planta Med (1991 Dec) 57(6):548-51 ISSN: 0032-0943 The new phloroglucinol derivative 1 has been isolated from the light petroleum ether extract of the aerial parts of Hypericum calycinum. Its structure has been established by means of 1H- and 13C-NMR spectroscopy and by nOe, MHQC, and HMBC experiments on its monomethyl ether derivative 3. Compound 1 was fungicidal against Cladosporium cucumerinum in a TLC bioassay. In addition, this new phloroglucinol derivative was also found to exert an interesting antimalarial activity in an in vitro test system. Registry Numbers: 108-73-6 (Phloroglucinol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Ishiguro K Yamaki M Kashihara M Takagi S Isoi K Sarothralin G: a new antimicrobial compound from Hypericum japonicum. In: Planta Med (1990 Jun) 56(3):274-6 ISSN: 0032-0943 A new antibiotic compound, sarothralin G from Hypericum japonicum Thunb. (Sarothra japonica) has been isolated and its structure was elucidated on the basis of spectroscopic data. The compound contains phloroglucinol and filicinic acid moieties. Registry Numbers: 108-73-6 (Phloroglucinol) 130756-15-9 (sarothralin G) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kartnig T Gobel I Heydel B Production of hypericin, pseudohypericin and flavonoids in cell cultures of various Hypericum species and their chemotypes. In: Planta Med (1996 Feb) 62(1):51-3 ISSN: 0032-0943 Suspension cultures were established from the shoots of sterile germinated seeds of various provenances of seven Hypericum (H.) species in a half strength modified Murashige and Skoog liquid medium. In most strains of H. perforatum (18 provenances) and all strains of H. maculatum (6 provenances) as well as in the cultures of H. tomentosum, H. bithynicum, H. glandulosum and H. balearicum, hypericin and pseudohypericin could be proven, however, in extremely varying amounts. In general, the pseudohypericin content was significantly higher than that of hypericin. The flavonoid patterns, comprising monomeric quercetin derivatives and dimeric apigenin derivatives, varied among strains over a wide range. Registry Numbers: 198-55-0 (Perylene) 548-04-9 (hypericin) 55954-61-5 (pseudohypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PROCEEDINGS/ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH***** Thomas C MacGill RS Neill P Pardini RS THE IN VITRO AND IN VIVO PHOTOINDUCED ANTINEOPLASTIC ACTIVITY OF HYPERICIN (MEETING ABSTRACT) In: Proc Annu Meet Am Assoc Cancer Res (1992) 33:A2989 ISSN: 0197-016X Hypericin, a polycyclic quinone obtained from plant species of the genus Hypericum, is capable of the photodynamic generation of singlet oxygen. The photodynamic effect of hypericin was investigated using EMT6 mouse mammary carcinoma cells in vitro and with MX-1 human mammary carcinoma in vivo. Cytotoxicity studies using EMT6 cells in tissue culture demonstrated a dose-dependant response from 1 to 50 uM hypericin in the presence of oxygen and light. Hypericin exhibited no cytotoxicity towards EMT6 cells in the dark or under anaerobic conditions. MX-1 human mammary carcinoma was grown in athymic mice and then treated with hypericin. Tumor-bearing mice were injected with 1 mg hypericin/kg body wt intratumorally 1x/wk for 3 wk. The tumors were irradiated at 24-, 72- and 120-hr post-treatment each week for a total dose of 100 J/wk at 600 nm. Tumors were measured weekly, and the results indicated that hypericin possesses significant antineoplastic activity towards MX-1 when irradiated. These results suggest that hypericin has potential as a second- generation photochemotherapeutic agent. Registry Numbers: 548-04-9 (hypericin) 198-55-0 (Perylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ****PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES** Meruelo D Lavie G Lavie D Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. In: Proc Natl Acad Sci U S A (1988 Jul) 85(14):5230-4 ISSN: 0027-8424 Two aromatic polycyclic diones hypericin and pseudohypericin have potent antiretroviral activity; these substances occur in plants of the Hypericum family. Both compounds are highly effective in preventing viral-induced manifestations that follow infections with a variety of retroviruses in vivo and in vitro. Pseudohypericin and hypericin probably interfere with viral infection and/or spread by direct inactivation of the virus or by preventing virus shedding, budding, or assembly at the cell membrane. These compounds have no apparent activity against the transcription, translation, or transport of viral proteins to the cell membrane and also no direct effect on the polymerase. This property distinguishes their mode of action from that of the major antiretro-virus group of nucleoside analogues. Hypericin and pseudohypericin have low in vitro cytotoxic activity at concentrations sufficient to produce dramatic antiviral effects in murine tissue culture model systems that use radiation leukemia and Friend viruses. Administration of these compounds to mice at the low doses sufficient to prevent retroviral-induced disease appears devoid of undesirable side effects. This lack of toxicity at therapeutic doses extends to humans, as these compounds have been tested in patients as antidepressants with apparent salutary effects. Our observations to date suggest that pseudohypericin and hypericin could become therapeutic tools against retroviral-induced diseases such as acquired immunodeficiency syndrome (AIDS). Registry Numbers: 198-55-0 (Perylene) 548-04-9 (hypericin) 55954-61-5 (pseudohypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PSYCHOPHARMACOLOGY BULLETIN***** Cott J NCDEU update. Natural product formulations available in europe for psychotropic indications. In: Psychopharmacol Bull (1995) 31(4):745-51 ISSN: 0048-5764 Until the middle of this century, development of medical treatment for human disease was intimately connected with the plant kingdom. Despite advances of the last three decades in utilizing chemical synthetic approaches to drug design and sophisticated structure- activity studies, there is still a great need for novel compounds with unique mechanisms of action in the field of medicine. While many thousands of structural analogs have been synthesized and tested, numerous gaps remain in the therapeutic armamentarium for psychiatric illnesses. Most new drugs marketed for psychotherapeutic indications in recent years have been only incremental improvements on existing medications. Major breakthroughs have resulted primarily from the study of natural products. Some of our most valuable drugs have been isolated from plant and animal sources, including aspirin, morphine, reserpine (the first antipsychotic), almost all of our antibiotics, digitalis, and such anti-cancer agents as vincristine, vinblastine, and taxol. Recent political and social events suggest that new emphasis will be placed on natural products research in the years to come. This article highlights therapeutic applications of Ginkgo biloba, Hypericum perforatum, Valerian officinalis, and Panex ginseng. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TIERARZTLICHE PRAXIS***** Kumper H [Hypericum poisoning in sheep] Hypericismus bei Schafen. In: Tierarztl Prax (1989) 17(3):257-61 ISSN: 0303-6286 (Published in German) A report about a case of St. John's wort poisoning in German Blackface sheep is given. After the ingestion of St. John's wort (Hypericum perforatum) all slightly pigmented parts of the skin, that were rarely covered with hair, were photosensitized. In summer many sheep suffered from inflammatory skin alterations at the ears, the bridge of the nose and at the surroundings of the eyes. A literature review informs about etiology and treatment of photosensitivity disease and the St. John's wort is exactly described to facilitate recognition. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TOXICOLOGY LETTERS***** Garrett BJ Cheeke PR Miranda CL Goeger DE Buhler DR Consumption of poisonous plants (Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-metabolizing enzymes. In: Toxicol Lett (1982 Feb) 10(2-3):183-8 ISSN: 0378-4274 Effect of dietary tancy ragwort (Senecio jacobaea), comfrey (Symphytum officinale), bracken (Pteridium aquilinum) and alfalfa (Medicago sativa) on hepatic drug-metabolizing enzymes in rats were measured. Tansy ragwort and bracken increased (P less than 0.05) the activity of glutathione transferase and epoxide hydrolase. Comfrey and alfalfa increased (P less than 0.05) the activity of aminopyrine N-demethylase. Feeding bracken or St. John's wort (Hypericum perforatum) in conjunction with tansy ragwort did not influence chronic toxicity of tansy ragwort as assessed by rat survival time. Dietary tansy ragwort resulted in increased (P less than 0.05) hepatic copper levels; the other plants did not affect copper levels. The results do not suggest any major interaction in the toxicity of tansy ragwort with bracken or St. John's wort. Registry Numbers: EC 2.5.1.18 (Glutathione Transferases) EC 3.3.2.3 (Epoxide Hydrolases) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Garrett BJ Cheeke PR Miranda CL Goeger DE Buhler DR CONSUMPTION OF POISONOUS PLANTS (SENECIO JACOBAEA, SYMPHYTUM OFFICINALE, PTERIDIUM AQUILINUM, HYPERICUM PERFORATUM) BY RATS: CHRONIC TOXICITY, MINERAL METABOLISM, AND HEPATIC DRUG-METABOLIZING ENZYMES In: Toxicol Lett (1982) 10(2/3):183-188 The effects of the carcinogenic plant comfrey (Symphytum officinale), tansy ragwort (Senecio jacobaea), and bracken (Pteridium aquilinum) on the activity of hepatic drug metabolizing enzymes in rats were investigated. Tansy ragwort and bracken increased the activity of glutathione transferase and epoxide hydrolase. Comfrey and alfalfa increased the activity of aminopyrine N-demethylase. Neither bracken nor St. John's wort (Hypericum perforatum) potentiated the toxicity of tansy ragwort as indicated by rat survival time. Apparently no major toxic interaction exists between tansy ragwort and bracken or St. John's wort. (13 Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****UROLOGIIA I NEFROLOGIIA***** Davidov MI Goriunov VG Kubarikov PG [Phytoperfusion of the bladder after adenomectomy] Fitoperfuziia mochevogo puzyria posle adenomektomii. In: Urol Nefrol (Mosk) (1995 Sep-Oct)(5):19-20 ISSN: 0042-1154 (Published in Russian) For continuous irrigation of the bladder after prostatic adenomectomy herb infusion (Urtica dioica L. 12-15 g/l, Hypericum perforatum L. 8- 12 g/l. Marticaria recutita L. 8-10 g/l, folia Plantaginis majoris 7- 10 g/l, Herba Millefolii 4-6 g/l, folia Betula 3-5 g/l. Artemisia vulgaris L. 1-2 g/l, folia Fragaria vesca 3-4 g/l, water 11 maximum) was dripped through a thin suprapubic and urethral drainages. Such phytoperfusion of the urinary bladder used in 22 patients reduced postoperative blood loss, bacteriuria, prevented hemorrhagic and purulent inflammation following adenomectomy. Side systemic effects were not reported. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VESTNIK OTORINOLARINGOLOGII***** Kliachko LL Ankhimova ES Svitina NN Iaremenko KV [The effect of medicinal herbs on lymphocyte rosette-forming function] Vliianie lekarstvennykh trav na rozetkoobrazuiushchuiu funktsiiu limfotsitov. In: Vestn Otorinolaringol (1994 Mar-Apr)(2):31-3 ISSN: 0042-4668 (Published in Russian) The blood samples from ENT patients with immunodeficiency were used in an in vitro trial of some herbs effect on T-lymphocyte rosette formation. Out of 10% infusions made of Hypericum L., Matricaria chamomilla L., Chelidonium L., Salvia officinalis L., Mentha L., stimulation of rosette formation was recorded only after introduction of Matricaria chamomilla L. and Chelidonium L. infusions. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VETERINARY AND HUMAN TOXICOLOGY***** Kako MD al-Sultan II Saleem AN Studies of sheep experimentally poisoned with Hypericum perforatum. In: Vet Hum Toxicol (1993 Aug) 35(4):298-300 ISSN: 0145-6296 Sheep given different dosages and frequencies of Hypericum perforatum had decreased hemoglobin, red blood cell count, packed cell volumes, total protein, glucose, cholesterol, triglycerides, and serum alkaline phosphotase activities. Blood urea nitrogen, sodium, potassium, bilrubin (total and direct), and the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma glutamyltransferase increased. Hemato- biochemical assays were useful diagnostic aids to determine the severity of this plant's toxic effects. Registry Numbers: 198-55-0 (Perylene) 548-04-9 (hypericin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€