€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BRITISH JOURNAL OF CANCER***** Woerdenbag HJ Lemstra W Malingre TM Konings AW Enhanced cytostatic activity of the sesquiterpene lactone eupatoriopicrin by glutathione depletion. In: Br J Cancer (1989 Jan) 59(1):68-75 ISSN: 0007-0920 Eupatoriopicrin (EUP), a sesquiterpene lactone from Eupatorium cannabinum L., possesses cytostatic activity. This was demonstrated for FIO 26 cells in vitro with the aid of a clonogenic assay and in vivo by tumour growth delay in FIO 26 and Lewis lung tumour-bearing mice. In vitro the IC50 for 1 h exposure to EUP was 1.5 microgram ml- 1 (4.1 nmol ml-1). This concentration depleted about 25% of its cellular GSH concentration. Pretreatment of FIO 26 cells with BSO, resulting in greater than 99%. GSH depletion, enhanced the cytotoxic effect of EUP. The dose-enhancement factor at the level of 10% cell survival was 2.3. Growth inhibition of the Lewis lung carcinoma and the FIO 26 fibrosarcoma, solidly growing in C57Bl mice, was found after i.v. injection of 20 or 40 mg kg-1 EUP, at a tumour volume of about 500 microliters. Pretreatment with BSO at a dose of 4 mmol kg-1 i.p., 6 h before EUP administration, resulted in a significantly stronger growth delay of both tumours compared with EUP only. At the time of EUP treatment, cellular GSH in the tumours was reduced by BSO treatment to about 60%. It is concluded that EUP possesses anti-tumour activity in vivo and that chemosensitisation of EUP may be accomplished by pretreatment with BSO, indicating that endogenous GSH protects against the cytostatic action of EUP. Registry Numbers: 1982-67-8 (Methionine Sulfoximine) 5072-26-4 (buthionine sulfoximine) 6856-01-5 (eupatoriopicrine) 70-18-8 (Glutathione) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF CHINESE MEDICINE***** Chan MY Zhao XL Ogle CW A comparative study on the hepatic toxicity and metabolism of Crotalaria assamica and Eupatorium species. In: Am J Chin Med (1989) 17(3-4):165-70 ISSN: 0192-415X The oral LD50 of Crotalaria assamica, which contains mainly monocrotaline, was found to be 154 mg/kg in mice. Neither liver necrosis nor morbidity was demonstrated with Eupatorium extract at a dose level of 144 mg/kg, which was equivalent to the LD20 of Crotalaria. Pretreatment with phenobarbitone enhanced the toxicity of both plant extracts in mice. In in vitro studies, "metabolic pyrrole" was formed by incubating Eupatorium japonicum extracts with liver microsomes. The rate of "pyrrole" formation was similar to that of Crotalaria extract and pure monocrotaline alkaloid, but was much slower than retrorsine. The rate of N-oxide formation was, in descending order, retrorsine, Eupatorium japonicum and Crotalaria/monocrotaline. It is concluded that the alkaloid in Eupatorium species is metabolized to "pyrrole" and an N-oxide metabolite in the liver, but hepatotoxicity is much lower when compared with that caused by Crotalaria. Registry Numbers: 315-22-0 (Monocrotaline) 50-06-6 (Phenobarbital) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Zhao XL Chan MY Kumana CR Ogle CW A comparative study on the pyrrolizidine alkaloid content and the pattern of hepatic pyrrolic metabolite accumulation in mice given extracts of Eupatorium plant species, Crotalaria assamica and an Indian herbal mixture. In: Am J Chin Med (1987) 15(1-2):59-67 ISSN: 0192-415X Plants belonging to the Eupatorium species, E. japonicum Thunb, E. fortunei and E. chinense, were found to contain very low concentrations of pyrrolizidine alkaloid compared with a known hepatotoxic Indian herbal mixture and Crotalaria assamica. High concentrations of pyrrolic metabolite were detected in livers of mice given a single oral dose of extracts of Indian herbal mixture or C. assamica but not in the case of the Eupatorium species. Also, accumulation of pyrrole metabolites was not demonstrated with chronic administration of decoctions prepared from herbs of the Eupatorium species. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Edgar JA Lin HJ Kumana CR Ng MM Pyrrolizidine alkaloid composition of three Chinese medicinal herbs, Eupatorium cannabinum, E. japonicum and Crotalaria assamica. In: Am J Chin Med (1992) 20(3-4):281-8 ISSN: 0192-415X The pyrrolizidine alkaloid composition of three Chinese herbs, "pei lan", "cheng gan cao" and "zi xiao rong," identified respectively as Eupatorium cannabinum, Eupatorium japonicum (Compositae) and Crotalaria assamica (Leguminosae), were studied by fast atom bombardment mass spectrometry and gas chromatography-electron impact mass spectrometry. Viridiflorine, cynaustraline, amabiline, supinine, echinatine, rinderine and isomers of these alkaloids were found in the Eupatorium species. Monocrotaline was the only pyrrolizidine alkaloid detected in the Crotalaria species. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Wagner H Jurcic K [Immunologic studies of plant combination preparations. In-vitro and in-vivo studies on the stimulation of phagocytosis] Immunologische Untersuchungen von pflanzlichen Kombinationspraparaten. In-vitro- und In-vivo-Studien zur Stimulierung der Phagozytosefahigkeit. In: Arzneimittelforschung (1991 Oct) 41(10):1072-6 ISSN: 0004-4172 (Published in German) The activity of phagocytosis was tested in the in vitro granulocyte test and the in vivo carbon-clearance-test in the mouse for an extract combination consisting of four plant extracts (Echinacea angustifolia, Eupatorium perfoliatum, Baptisia tinctoria and Arnica montana). In both immune models, a step by step stimulation of the activity of phagocytosis by the addition of the four plant extracts was shown with an increase in effectiveness of partially over 50% in comparison to the pure Echinacea angustifolia mono-extract. The extract combination showed also in both test models a higher efficiency than two other differently composed combination preparations and two Echinacea mono-preparations. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH***** Carvalho LH Brandao MG Santos-Filho D Lopes JL Krettli AU Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture. In: Braz J Med Biol Res (1991) 24(11):1113-23 ISSN: 0100-879X 1. Ninety-five crude extracts obtained with either organic solvents or water from 48 Brazilian plants or parts of plants were evaluated experimentally as blood schizontocides. Seventy-three extracts were obtained from 33 plants randomly collected using an empirical approach, and 22 from 15 "medicinal" plants. 2. The crude extracts were screened in vivo at up to 1.0 g/kg, po, for 4 days in mice infected with blood forms of Plasmodium berghei and parasitemia was determined on the fifth day. 3. Six plants, 2 randomly collected, Vernonia brasiliana and Eupatorium squalidum, and 4 "medicinal" plants, Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus, and Tachia guianensis, were partly active against the rodent malaria, i.e., they showed 40-50% inhibition of P. berghei multiplication. Forty-two plants whose extracts presented no antimalarial activity are reported. 4. Four extracts with antimalarial activity were also tested in vitro using P. falciparum cultures and two of them, V. brasiliana and A. australe, were active. Extracts of V. brasiliana caused about 50% inhibition of parasite multiplication at relatively low doses (40 ng/ml) as compared to chloroquine (30 ng/ml) and quinine (50 ng/ml). 5. The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Han SP Feng YX [Constituents in volatile oil of peilan and 3 plants of the same genus] In: Chung Kuo Chung Yao Tsa Chih (1993 Jan) 18(1):39-41, 63 ISSN: 1001-5302 (Published in Chinese) A study hes been made on the essential oil from the crude drug Peilan (Eupatorium fortunei) and the plants E. japonicum, E. chinense and E. cannabinum. 71 constituents have been identified by GC-MS. Quantitative analysis has been carried out by GC. The study provides scientific methods for the identification of the crude drug "Peilan" and the quality control of the fresh and dried "Peilan". Registry Numbers: 464-17-5 (bornylene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ANIMAL SCIENCE***** Panter KE James LF Natural plant toxicants in milk: a review. In: J Anim Sci (1990 Mar) 68(3):892-904 ISSN: 0021-8812 Elimination of plant toxicants via milk by lactating animals is considered a minor route of excretion; however, it may be important when the health of the neonate or food safety in humans is considered. Among plant toxicants excreted in milk is tremetol or tremetone, the toxin in white snakeroot (Eupatorium rugosum) and rayless goldenrod (Haplopappus heterophyllus). These plants have been responsible for intoxication of cows and their suckling calves and for many human poisonings. Other plant toxins excreted through the milk that pose a toxicity hazard include pyrrolizidine alkaloids in Senecio, Crotalaria, Heliotropium, Echium, Amsinckia, Symphytum (comfrey), Cynoglossum (hounds tongue) and Festuca (tall fescue); piperidine alkaloids in Conium, tobacco and others; quinolizidine alkaloids in Lupinus; sesquiterpene lactones of bitterweed and rubber weed; and glucosinolates in Amoracia (horseradish), Brassica (cabbage, broccoli, etc.), Limnanthes (meadowfoam), Nasturtium (watercress), Raphanus (radish) and Thlaspi (stinkweed). Many plants such as Astragalus, Oonopsis, Stanleya, Xylorrhiza, Aster, Atriplex, Sideranthus and Machaeranthera accumulate selenium and may cause intoxication when grazed. Selenium is found in the milk at concentrations relative to the amounts ingested by the lactating animal. Excretion of selenium via the milk is important in the deficiency state, but when in excess it may cause toxicity to offspring. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CLINICAL LABORATORY ANALYSIS***** Elsasser-Beile U Willenbacher W Bartsch HH Gallati H Schulte Monting J von Kleist S Cytokine production in leukocyte cultures during therapy with Echinacea extract. In: J Clin Lab Anal (1996) 10(6):441-5 ISSN: 0887-8013 We measured the levels of the cytokines IL-1-alpha, IL-1-beta, IL-2, IL-6, TNF-alpha, and IFN-gamma in culture supernatants of stimulated whole blood cells derived from 23 tumor patients undergoing a 4-week oral treatment with a spagyric extract from Echinacea angustifolia, Eupatorium perfoliatum, and Thuja occidentalis (Echinacea complex). All patients had had curative surgery for a localized solid malignant tumor. Blood was taken before treatment and after 2 and 4 weeks of therapy. Twelve untreated tumor patients at the same clinical stage, also after curative surgery, served as a control group. In the blood cell cultures of all patients, a rather wide range of cytokine levels was found. After therapy with Echinacea complex, no significant alteration in the production of the cytokines could be seen in comparison to the controls, and also the leukocyte populations remained constant. We conclude that at this application and dosage, the therapy with Echinacea complex has no detectable effect on tumor patients' lymphocytes activity as measured by their cytokine production. Registry Numbers: 82115-62-6 (Interferon Type II) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Caceres A Menendez H Mendez E Cohobon E Samayoa BE Jauregui E Peralta E Carrillo G Antigonorrhoeal activity of plants used in Guatemala for the treatment of sexually transmitted diseases. In: J Ethnopharmacol (1995 Oct) 48(2):85-8 ISSN: 0378-8741 Plants popularly used in Guatemala for the treatment of gonorrhoea were macerated in 50% alcohol and the tincture tested for in vitro activity against Neisseria gonorrhoeae using strains isolated from symptomatic patients and confirmed by standard bacteriological procedures. From 46 plants investigated, 13 (28.3%) showed evident inhibition zones (> 9 mm), seven (15.2%) showed small activity (6.1- 8.9 mm) and 26 (56.5%) showed no activity; nine of these plants inhibited five strains of N. gonorrhoea freshly isolated. The most active plants of American origin were: bark of Bixa orellana fruits of Parmentiera edulis, leaf of Diphysa robinioides, Eupatorium odoratum, Gliricidia sepium, Physalis angulata, Piper aduncum and Prosopis juliflora, root of Casimiroa edulis, and whole Clematis dioica. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND***** Triratana T Suwannuraks R Naengchomnong W Effect of Eupatorium odoratum on blood coagulation. In: J Med Assoc Thai (1991 May) 74(5):283-7 ISSN: 0125-2208 The purified compound, 4', 5, 6, 7-tetramethoxyflavone, is an active ingredient isolated from Eupatorium odoratum, a Thai indigenous plant that has long been used to stop bleeding. This compound was studied in vitro for the effect on blood clotting factor activities. It was found that the compound enhanced blood coagulation, the observed APTT being shorter than that observed in the control. The result suggested that the compound accelerated clotting time through the intrinsic pathway of the coagulation which may involve the reaction of factor XII, factor XI, factor IX or factor VIII. Registry Numbers: 1168-42-9 (4',5,6,7-tetramethoxyflavone) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MEMORIAS DO INSTITUTO OSWALDO CRUZ***** Carvalho LH Krettli AU Antimalarial chemotherapy with natural products and chemically defined molecules. In: Mem Inst Oswaldo Cruz (1991) 86 Suppl 2:181-4 ISSN: 0074-0276 In the present work we have described the in vivo antimalarial activity of six different plants. Two of them (Vernonia brasiliana and Eupatorium squalidum) were tested in a randomic approach among 273 crude extracts from plants; four (Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus and Tachia guianensis) were selected after screening 22 crude extracts from different medicinal plants used in Brazil against fever and/or malaria. We also studied chemically defined molecules and some of them showed antimalarial activity in vitro. Some aspects of recent research with natural products aiming to produce drugs are discussed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NATURAL TOXINS***** Oelrichs PB Calanasan CA MacLeod JK Seawright AA Ng JC Isolation of a compound from Eupatorium adenophorum (Spreng.) [Ageratina adenophora (Spreng.)] causing hepatotoxicity in mice. In: Nat Toxins (1995) 3(5):350-4 ISSN: 1056-9014 Regular ingestion of Eupatorium adenophorum [Ageratina adenophora (Spreng.)] or Crofton weed causes chronic pulmonary disease in horses mainly in Australia, New Zealand, and the Himalayas. The disease is characterized by pulmonary interstitial fibrosis, emphysema, alveolar epithelisation and reduced tolerance to exercise. Horses apparently are the only animals affected and there are numerous reports of farms losing all their horses. The disorder was produced experimentally in horse feeding trials, and it was shown that characteristic lesions occurred in the lungs. In studies with laboratory animals, mice were shown to be suitable test animals, but in this species lesions occur in the liver rather than the lungs. The hepatic injury in these animals is characterized by multiple areas of focal necrosis of the parenchyma associated with degeneration and loss of the epithelium lining the small bile ducts. The active principle 9-oxo-10,11 dehydroagerophorone responsible for these lesions in mice has been isolated from E. adenophorum. Although the compound has been shown to exhibit toxicity to larvae of invertebrate species, no mammalian toxicity studies have been previously reported involving the isolated toxin. The mechanism of the toxic effect of the compound as well as its possible relevance to the respiratory disease in the horse remain to be investigated. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Beier RC Norman JO Reagor JC Rees MS Mundy BP Isolation of the major component in white snakeroot that is toxic after microsomal activation: possible explanation of sporadic toxicity of white snakeroot plants and extracts. In: Nat Toxins (1993) 1(5):286-93 ISSN: 1056-9014 Tremetone, the major toxic component in white snakeroot (Eupatorium rugosum Houtt) extracts, was isolated following an in vitro bioactivity assay. Microsomal activation was required to produce a product toxic to murine melanoma (B16F1) cells as well as five other mammalian cell cultures. The metabolic activation product(s) of tremetone is suspected to be responsible for the toxic activity of the plant. Tremetone is also smoothly converted to dehydrotremetone in the plant and cell free homogenates, and readily decomposes to dehydrotremetone in extracts. Dehydrotremetone is not toxic even after microsomal activation. The efficient conversion of tremetone to dehydrotremetone may explain why white snakeroot plant material and extracts have varied activities, and why a previous claim that tremetone was responsible for the toxic activity of white snakeroot was withdrawn. Rayless goldenrod extracts show the same toxic activity as white snakeroot and the toxic activity of rayless goldenrod is most likely due to tremetone. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Lexa A Fleurentin J Lehr PR Mortier F Pruvost M Pelt JM Choleretic and hepatoprotective properties of Eupatorium cannabinum in the rat. In: Planta Med (1989 Apr) 55(2):127-32 ISSN: 0032-0943 According to our results, the traditional therapeutic indications of Eupatorium cannabinum L., choleretic and hepatoprotective effects, have been widely demonstrated. An aqueous extract induces hypercholeresis in the rat, the site of bile formation is canalicular in origin and both bile acid-dependent and bile acid-independent flows could be stimulated; the extract possesses anti-necrotic properties against carbon tetrachloride-induced hepatotoxicity, reducing widely the plasma GPT level in pretreated rats. Registry Numbers: 149-32-6 (Erythritol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VETERINARY AND HUMAN TOXICOLOGY***** Beier RC Norman JO The toxic factor in white snakeroot: identity, analysis and prevention. In: Vet Hum Toxicol (1990) 32 Suppl:81-8 ISSN: 0145-6296 White snakeroot (Eupatorium rugosum Houtt) has been known to cause trembles in animals and milk sickness in humans since the American Revolution. It still continues to poison animals. Horses and goats are particularly sensitive to white snakeroot poisoning. Resurgence of livestock production on small farm units, and utilization of fresh raw milk may result in milk sickness; if the animals have white snakeroot exposure. The goat is the only animal with good toxicity threshold data. In other animals and humans the toxicity thresholds of white snakeroot are not known, and that until responsible toxic principles are identified and their fate in animals and milk studied, such an assessment will not be possible. The toxic component(s) in white snakeroot has not been identified. The mechanism of action of the toxin in animals or humans remains unknown. However, metabolic studies in chicks initially suggest that a specific metabolic enzyme may be the target of the toxic principle. Components of white snakeroot that are toxic after microsomal activation have been isolated. Cytochrome P-450 is responsible for this activation. Activation in vitro can be totally inhibited by the cytochrome P-450 specific autocatalytic inhibitor, 1-aminobenzotriazole. In view of the importance of white snakeroot in the history of the United States and the ongoing problems today, it would be most unfortunate if studies were not pursued expeditiously to identify the toxicant(s) responsible, and to understand the mechanism(s) of action and toxicity thresholds. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€