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Contribution to the knowledge of the folk plant medicine in Calabria region (Southern Italy).

A series of research on plants used in Calabria (Southern Italy) in the folk plant medicine was carried out in the last twenty years. The use of 104 taxa distributed into 42 families are described. Among the major findings: Ceterach officinarum as hypotensive; Heliotropium europaeum in the case of urinary inflammations; Silybum marianum for haemorrhoids; Arundo donax for pertussis and cystitis; Allium cepa for sties and flu; Laurus nobilis as galactagogue; Passiflora incarnata for burns, haemorrhoids and skin inflammations; Scrophularia canina for rhagas and wounds; Urtica membranacea for tussis and tonsillitis.

Ethnobotany↗

An outbreak of hepatic veno-occlusive disease in north-western Afghanistan.

Following a 2-year period of severe drought a very large number of patients with massive ascites and emaciation were observed in north-western Afghanistan. Clinicopathological study showed that these were typical cases of hepatic veno-occlusive disease. The outbreak was caused by consumption of bread made from wheat contiminated with seeds of Heliotropium plants, which were shown to contain pyrrolizidine alkaloids. Examination of 7200 inhabitants from the affected villages showed evidence of liver disease in 22.6%. Clinical improvement was observed in thirteen cases after 3 to 9 months of supportive hospital treatment, and in three cases liver biopsies showed almost complete disappearance of initial abnormalities.

Adolescent↗

Nitrogen fixers in the rhizosphere of certain desert plants.

Six species of common desert range plants; Achillea sp., Aristida plumosa, Artemisia herba-alba, Haloxylon articulatum, and Heliotropium ramosissimum were colleted from Western Desert in Iraq. Counts of Azotobacter spp. and total bacteria were estimated in both rhizosphere and non-rhizosphere soils. Biomass and total nitrogen content of the plants were determined. The R/N ratio (ratio between rhizosphere to non-rhizosphere) for Azotobacter sp. ranged between 1 to 19.5 with an average of 4.96. The number of Azotobacter in the rhizosphere ranged between 6.8 X 10(3) to 47 X 10(3) cells/g, while in the non-rhizosphere it ranged from 2 X 10(3) to 21 X 10(3). Aristida plumosa harboured the highest number, i.e., 47 X 10(3) cells/g, while Artemisia herba-alba showed the least, i.e., 6.8 X 10(3) cells/g. Total counts of bacteria in the rhizosphere ranged between 17.2 X 10(6) and 97 X 10(6) cells/g, that of the non-rhizosphere between 1.5 X 10(6) and 18 X 10(6) cells/g. The R/N ratio ranged between 2.03 X 22.5 with an average of 7.28. An appreciable gain of dry weight and total nitrogen was observed. Between 13 and 152 g with an average of 78.9 g dry weight and between 347 and 6684.0 mg with an average of 2452.0 mg nitrogen per plant were found. The possible contribution of Azotobacter to the nitrogen economy of the plants is discussed and further suggested.

Azotobacter↗

Solid-phase extraction and LC-MS analysis of pyrrolizidine alkaloids in honeys.

Strong-cation-exchange, solid-phase extraction of pyrrolizidine alkaloids and their N-oxides from honey samples was followed by reduction of the N-oxides and subsequent analysis of total pyrrolizidine alkaloids using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. A limited survey of 63 preprocessing samples of honey, purposefully biased toward honeys attributed to floral sources known to produce pyrrolizidine alkaloids, demonstrated levels of pyrrolizidine alkaloids up to approximately 2000 parts per billion (ppb) in a sample attributed to Echium plantagineum. Up to 800 ppb pyrrolizidine alkaloids was detected in some honeys not attributed by the collector to any pyrrolizidine alkaloid-producing floral source. No pyrrolizidine alkaloids were detected in approximately 30% of the samples in this limited study, while some honeys showed the copresence of pyrrolizidine alkaloids from multiple floral sources such as E. plantagineum and Heliotropium europaeum. In addition, retail samples of blended honeys (with no labeling to suggest that pyrrolizidine alkaloid-producing floral sources were used in the blends) have been shown to contain up to approximately 250 ppb pyrrolizidine alkaloids.

Chromatography, High Pressure Liquid↗

Evaluation of the biological activity of crude extracts from plants used in Yucatecan traditional medicine. Part II. DNA-interacting activity.

Extracts from leaves, stems, and roots of twelve plants used commonly in Yucatecan traditional medicine were evaluated in the DNA-methyl green assay. Twenty one extracts showed DNA-interacting activity, and nine of them, belonging to five plant species, presented a displacement activity of 5% or higher. The highest activity (17.6%) was detected in the leaf extract of Heliotropium angiospermum.

DNA↗

Handling toxicoses of unknown origin.

A strategy is presented for investigating toxicoses of unknown origin and following a disease-oriented approach. The strategy is derived from and illustrated by experience of three large scale outbreaks of disease involving aflatoxicosis in India, intoxication by pyrrolizidine alkaloids from Heliotropium spp. in Afghanistan and from Crotalaria spp. in India. Investigation of such cases involves a descriptive phase (case definition, descriptive pattern of disease), hypothesis generation (based on pathologic studies and indications from environmental and epidemiological investigations), hypothesis testing and confirmatory studies. After establishing a causal relationship, steps need to be taken to transmit information to health authorities, to disseminate knowledge to health delivery personnel and the general public, to identify borderline cases and plan management, to identify mechanisms of exposure/contamination and relevant measures to remove or minimize exposure to the causal agent.

Afghanistan↗

Assaying ornithine and arginine decarboxylases in some plant species.

A release of (14)CO(2) not related to ornithine decarboxylase activity was found in crude leaf extracts from Lycopersicon esculentum, Avena sativa, and especially from the pyrrolizidine alkaloid-bearing Heliotropium angiospermum when incubated with [1-(14)C]- or [U-(14)C]ornithine. The total (14)CO(2) produced was about 5- to 100-fold higher than that due to ornithine decarboxylase activities calculated from labeled putrescine (Put) found by thin-layer electrophoresis in the incubation mixtures. Partial purification with (NH(4))(2)SO(4) did not eliminate completely the interfering decarboxylation. When incubated with labeled arginine, a very significant (14)CO(2) release not related to arginine decarboxylase activity was observed only in extracts from H. angiospermum leaves, especially in Tris.HCl buffer. Under the assay conditions, these extracts exhibited oxidative degradation of added Put and agmatine (Agm) and also revealed a high arginase activity. Amino-guanidine at 0.1 to 0.2 millimolar prevented Put degradation and greatly decreased oxidative degradation of Agm; ornithine at 15 to 20 millimolar significantly inhibited arginase activity. A verification of the reliability of the standard (14)CO(2)-based method by assessing labeled Put and/or Agm-formed in the presence of added aminoguanidine and/or ornithine when needed-is recommended especially when crude or semicrude plant extracts are assayed.When based on Put and/or Agm formed at 1.0 to 2.5 millimolar of substrate, the activities of ornithine decarboxylase and arginine decarboxylase in the youngest leaves of the tested species ranged between 1.1 and 3.6 and 1 and 1600 nanomoles per hour per gram fresh weight, respectively. The enzyme activities are discussed in relation to the biosynthesis of pyrrolizidine alkaloids.

Journal Article↗

Bromosulphophthalein clearance rates in sheep with pyrrolizidine liver damage.

Sheep fed a ration containing 50% of dried Heliotropium europaeum showed a marked decline in bromosulphophthalein (BSP) fractional clearance rate during the first 3 months feeding. Thereafter, the response of individual animals varied widely on a time basis, although 3 groups could be identified. In the terminal stages, mean clearance rates were below 20% of initial values, with some sheep showing a decline in excess of 90%. Loss of liver functional capacity was generally much greater than indicated by the degree of damage revealed by histopathology. Thus, a suitably modified test could have considerable prognostic value in the field. In this investigation, all sheep with clearance rates below 0.15 died when exposed to a further period of H. europaeum feeding.

Animal Feed↗

Pyrrolizidine alkaloid poisoning of sheep in New South Wales.

Pyrrolizidine alkaloid poisoning of sheep in New South Wales was reviewed, based on the records of the New South Wales Department of Agriculture's Regional Veterinary Laboratories. The plant species causing significant mortalities were Echium plantagineum and Heliotropium europaeum. The syndrome of hepatogenous chronic copper poisoning was more frequently diagnosed than primary pyrrolizidine alkaloid poisoning, particularly when grazing E. plantagineum. The data indicated that adult crossbred ewes were the most commonly affected class of sheep.

Animals↗

Herbal medicines and veno-occlusive disease in India.

Six cases are described of veno-occlusive disease (VOD) after medicinal herb ingestion. The herb Heliotropium eichwaldii, taken by three patients, was found to contain the toxic pyrrolizidine alkaloid, heliotrine. Two patients presented with fulminant hepatic failure while the other four patients had a clinical picture suggestive of decompensated cirrhosis. The medical use of this herb may possibly be responsible for a significant proportion of acute and chronic liver disease in India, making it of public health importance.

Humans↗

Natural plant toxicants in milk: a review.

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.

Animals↗

Toxicity and metabolism of pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PA) are found mainly in plants of three families: boraginaceae, Compositae and Leguminosae. In North America, PA poisoning of livestock is caused primarily by consumption of Senecio and Crotalaria spp. The PA of Senecio spp. cause irreversible hepatic damage; toxicity signs are a consequence of impaired liver function. Crotalaria intoxication leads to pulmonary damage as a primary effect; hepatic effects are less prominent. Large species differences exist in susceptibility to PA toxicosis. Small herbivores such as sheep, goats, rabbits, guinea pigs and other herbivorous laboratory animals are highly resistant to PA toxicity, associated with a low rate of hepatic production of reactive metabolites (pyrroles) and(or) a high rate of activity of detoxifying enzymes. Diester PA common to Heliotropium and Echium spp. are metabolized in the ovine rumen to 1-methyl metabolites, whereas the macrocyclic ester PA of Senecio spp. are not. Exposure to PA results in high concentrations of liver Cu, reduced liver Zn, and abnormal Fe metabolism with hematopoiesis markedly impaired. Pyrrolizidine alkaloid toxicity alters vitamin A metabolism in rats, depressing plasma and liver levels of vitamin A. Synthetic antioxidants in the diet confer protective activity in laboratory animals (e.g., rats, mice) against PA toxicoses. The PA and their metabolites are secreted in the milk of lactating animals, but this probably does not represent a significant human health hazard.

Animals↗

[Plant extracts with cytostatic properties growing in Cuba. II].

The study of the cytostatic activity of aqueous, alcoholic and ketonic extracts from 18 parts of 9 species of superior plants of the families Araceae, Borraginacease, Burseraceae, Cesalpinaceae, Meliaceae, Compositae, Rebiaceae, Cruciferaceae and Verbenaceae using the microbiologic method of described by Kubas in 1972 is pursued. The best results were obtained from Hamelia patens. Lippia alba, Lepidium virginicum, Cassia ligustrina, Bursera simaruba and Heliotropium campechianum extracts.

Cell Division↗

[Biological evaluation of Cuban plants. V].

The study of the antimicrobial activity of aqueuos, alcoholic and ketonic extracts from plants growing in Cuba is pursued. Six species of the families Rutaceae, Portulacaceae, Borraglinaceae and Jasminaceae were analyzed, and their activity on bacteria with a human clinical interest was assessed. The best results were obtained from Heliotropium campechianum, Jazminum sambac and Portulaca oleracea.

Anti-Bacterial Agents↗

Phase I study of indicine N-oxide in patients with advanced cancer.

Indicine N-oxide is a pyrrolizidine alkaloid isolated from Heliotropium indicum, one of the widely used herbs in Ayurvedic medicine. Thirty-seven patients with solid tumors received the drug: 15 men and 22 women (mean age, 53 years). All had had prior chemotherapy, and 25 had had prior radiotherapy. Eighty-four percent had a performance status of 0-3 (Cancer and Leukemia Group B criteria). The drug was given as a short infusion over 15 minutes and repeated with a median interval of 4 weeks. Doses were escalated from 1 to 9 g/m2. A total of 55 courses were evaluable. Dose-limiting toxic effects were leukopenia and thrombocytopenia, and the toxicity was cumulative with repeated doses. Other toxic effects included nausea and vomiting, anemia, and hepatic dysfunction. The hematologic toxicity tended to be more pronounced in patients with hepatic dysfunction, poor marrow reserve, and heavy prior chemotherapy and radiotherapy. There were no complete or partial responses. One patient with skin melanoma and another with ovarian carcinoma had improvement lasting 2 months. The maximally tolerated dose is 9 g/m2 in our population. A recommended dose for therapeutic study is 7 g/m2. High-risk patients should be started at a dose of 5 g/m2. The treatment may be repeated at 4-week intervals with close monitoring of wbc and platelet counts. Dose reductions may be necessary for repeated courses.

Adult↗

An epidemic of veno-occlusive disease of the liver in Afghanistan. Pathologic features.

A large outbreak of veno-occlusive disease occurred in Afghanistan in which approximately 7,800 in a population of 35,000 subjects were estimated to have been affected. It was caused by consumption of wheat flour heavily contaminated with seeds of a plant of the heliotropium species. These were found to contain pyrrolizidine alkaloids, chiefly heliotrine. Fourteen percutaneous liver biopsies, representing different stages of diseases and liver tissue from eight autopsies were studied. Morphological changes in the liver were characteristic. Centrilobular hemorrhagic necrosis was followed by occlusive changes in the hepatic veins, finally resulting in nonportal cirrhosis. The sequence of changes observed suggests primary parenchymal injury and possibly obstructive lesions at the sinusoidal level. Collagenization of the sinusoids and reorganization of the lobular reticulin begin early in disease. Occlusive changes in the efferent veins apparently follow.

Afghanistan↗

[Liver involvement in the course of phytotherapy].

The development of herbal medicine has follow in line with increased popular interest in ecology. Emphasis has been placed on the safety of natural herbs in contrast with the risks involved with "classical" medicines. But recent publications have revealed that several herbal medicines are toxic for the liver. For example, in France we have observed cases of hepatitis after ingestion of germander (Teucrium chamaedrys). Clinicians should also be aware of other well documented toxic effects of herbs used in popular medicines in Africa, Asia or Central America. The toxicity of pyrrolizidine alkaloids was recognized over 40 years ago. More than 300 plant species, including Heliotropium, Crotalaria, Senecio and Symphytum, are implicated. In Africa or Central America, intoxication is sometimes endemic since these plants are often used for making tea. In Western countries, cases of herb-induced hepatitis have been observed after use of preparations containing Symphytum or Chinese herbs. Pyrrolizidine alkaloids cause obstruction of the hepatic venous system and can lead to hepatonecrosis. Clinical manifestations include abdominal pain, ascitis, hepatomegaly and raised serum transaminase levels. Prognosis is often poor with death rates of 20 to 30% being reported. Atractylis gummifera is another example of herbal toxicity. Twenty-six species of this plant are used for medicinal purposes or for chewing gum. Intoxication usually occurs in the spring and is related to chewing the roots of these plants. Severe hepatocellular lysis may occur less than 24 hours after ingestion. Clinical manifestations are related to the induced hypoglycemia and neurovegetative disorders or subsequent renal failure. These compounds have an inhibitor effect on the Krebs cycle and can lead to severe or fatal liver failure. Other similar cases of fatal liver accidents have been reported after ingesting Callilepis laureola, a herb used by the Zoulous in Natal for medicinal purposes or after use of products containing extracts of Teucrium chamaedrys, which was nevertheless authorized in France in 1986 for use in preparations for weight loss. These examples emphasize the importance of remembering that herbal medicine is not harmless. Faced with the extensive distribution of many herbal preparations and the risk of self-medication, consumers and clinicians alike should be increasingly vigilant with these potentially hepatotoxic products.

Chemical and Drug Induced Liver Injury↗