Pyrrolizidine alkaloids in medicinal plants from North America.

Pyrrolizidine alkaloids (PAs) are mutagenic, carcinogenic, pneumotoxic, teratogenic and fetotoxic. Plants containing PAs commonly poison livestock in many countries, including the USA and Canada. In some regions of the world PA-producing plants sometimes grow in grain crops and items of food made with PA contaminated grain, such as bread baked using contaminated flour, have been, and continue to be, responsible for large incidents of acute, often fatal human poisoning. Herbal medicines and food supplements containing PAs are also recognized as a significant cause of human poisoning and it is desirable that such medications are identified and subjected to strict regulation. In this review we consider the PAs known to be, or likely to be, present in both the traditionally used medicinal plants of North America and also medicinal plants that have been introduced from other countries and are being recommended and used as phytopharmaceuticals in the USA and Canada.

Toxic pyrrolizidinalkaloids as undesired contaminants in food and feed: degradation of the PAs from Senecio jacobaea in silage.

Pyrrolizidine alkaloids (PAs) can show a hazardous potential for men and animals. They can act as cancerogenic, mutagenic, teratogenic and fetotoxic agents. One pathway of a human intoxication is its occurence as contaminants in food and feed. Here, the contamination of cereals already led to severe and fatal intoxication episodes. Besides this, milk is of special concern as it is the main food for children which show a very high susceptibility for a PA intoxication. Milk can contain PAs in case the milk producing animals have access to contaminated feed. In this context it is of special interest whether the PA content of contaminated silage remains stable during the ensiling procedure or show a more or less high level of decomposition. We could show that ensiling will not lead to PA-free silage.

Plants containing pyrrolizidine alkaloids used in the traditional Indian medicine--including ayurveda.

Pyrrolizidine alkaloids (PAs) show a hazardous potential for humans and animals. They can possess mutagenic, teratogenic, cancerogenic and fetotoxic properties. One pathway of a human intoxication can be the use of medicinal plants which contain toxic PAs. The Traditional Indian medicine--in particular Ayurveda--is a popular and well-known healing system. Within this system several PA-containing plants are used which, on account of their PA level, represent a severe health risk. In general, it is not recommended to use plants containing those toxic compounds.

Pyrrolizidine alkaloids in plants used in the traditional medicine of Madagascar and the Mascarene islands.

Pyrrolizidine alkaloids (PAs) can be hazardous to the health of humans and animals. Although their toxicity has been known for a long time, PA containing plants are still in use in many traditional medicines. Traditional healing systems have become of increasing interest as many people believe that they can be used without any risk and side effects. This also applies to the traditional medicine of Madagascar and the Mascarene island (Mauritius, Reunion, Rodriguez). Recent literature reports have recommended this traditional medicine because of its good efficacy and pharmacological properties. However, several plants are listed there which have already been described to contain toxic PAs or are suspected of containing them.

Plants containing pyrrolizidine alkaloids: toxicity and problems.

Pyrrolizidine alkaloids (PA) are toxic for human and livestock. They undergo a metabolic toxication process in the liver which is the first target organ for PA poisoning. Worldwide many episodes of human PA intoxications are well reported. In many cases the reason for these intoxications has been PA contamination in food. The main tools for analysing food and fodder on PA content are based on GC and HPLC separation, followed by MS(-MS) detection. Actual incidents with toxic PA are the 'Jacobaea vulgaris (syn. Senecio jacobaea) problem' in Europe and the 'Ageratum conyzoides problem' in Ethiopia.

Lycopsamine and cumambrin B from Eupatorium maculatum.

The pyrrolizidine alkaloid (PA) lycopsamine and the guaianolide cumambrin B were isolated from Eupatorium maculatum L. Their structures were elucidated by spectroscopical methods.

Pyrrolizidine alkaloids in medicinal plants of Mongolia, Nepal and Tibet.

Pyrrolizidine alkaloids (PAs) are widely distributed in many plant families. Most of them are hazardous for humans and domestic animals. PA also occur in many medicinal plants. This is of importance because in Western countries the use of plants or preparations of them is more and more increasing. Especially plants of the Traditional Chinese Medicine (TCM) have increased in popularity. Similarly, people are also focused on medicinal plants from other traditional medicines. Nowadays the Traditional Mongolian Medicine (TMM), the Traditional Nepalese Medicine (TNM), and the Tibetan System of Medicine (TSM) are becoming more and more of interest. In those countries application of those phytopharmaceutics is based on its traditional use but a scientific investigation--especially for possible toxic side-effects--is often missing. This paper gives an overview on traditionally used plants from Nepal, Mongolia and Tibet with respect to its content or its possible content of pyrrolizidine alkaloids.

Phytochemical and analytical studies of extracts from Rhodiola rosea and Rhodiola quadrifida.

Column chromatography of hydrophilic extracts from Rhodiola rosea and Rodiola quadrifida led to the isolation of cinnamic alcohol, chlorogenic acid, rhodiooctanoside, rosiridin, rosavin and the phenolic compounds salidroside, rhodiolin and a novel compound consisting of viridoside with an attached arabinose unit (mongrhoside). HPLC analysis of plant material from different sources and from different collection periods showed a great variability in the composition and in the amount of pharmacologically active compounds contained.

Pyrrolizidine alkaloid level in Senecio bicolor (Wilid.) Tod, ssp. cineraria (DC.) from middle Europe.

From Senecio bicolor, ssp. cineraria, cultivated in middle Europe, seven pyrrolizidine alkaloids (PA) were isolated and their structures elucidated by spectroscopical methods. Besides the already known senecionine, integerrimine, seneciphylline, jacobine, jacoline and jaconine the jacobine-acetate was found. On account of structure toxicity relationship all PA show toxic side-effects.

The shikonin derivatives and pyrrolizidine alkaloids in hairy root cultures of Lithospermum canescens (Michx.) Lehm.

Hairy root cultures of Lithospermum canescens were established using three strains of Agrobacterium rhizogenes: ATCC 15834, LBA 9402 and NCIB 8196. Eight lines resulting from infection with A. rhizogenes ATCC 15834 demonstrated sufficient biomass increase and were submitted to further investigations. The contents of acetylshikonin (ACS) and isobutyrylshikonin (IBS) in transformed hairy roots made up ca. 10% of those observed in natural roots of L. canescens (24.35 and 14.48 mg g(-1) DW, respectively). One line, Lc1-D, produced the largest amounts of ACS (2.72 mg g(-1) DW) and IBS (0.307 mg g(-1) DW). Traces of pyrrolizidine alkaloids (PA), canescine and canescenine, were found in all lines of transformed hairy roots.

Immunomodulatory effect of shikonin derivatives isolated from Lithospermum canescens on cellular and humoral immunity in Balb/c mice.

The immunomodulatory activity of acetylshikonin (ACS) and isobutyrylshikonin (IBS) was studied in female and male inbred Balb/c mice, and in F1 hybrids (Balb/c x C3H). ACS and IBS were isolated from Lithospermum canescens Lehm. (Boraginaceae) roots. Splenocytes from mice fed 40 microg of ACS had higher proliferative potential in cultures with PHA than corresponding controls and also higher migratory in vitro activity than splenocytes obtained from control animals. ACS at a 40 microg daily dose stimulated G-v-H reaction but inhibited it at a 200 microg dose. IBS at a 40 microg dose significantly increased humoral response.

Veno-occlusive disease in a fetus caused by pyrrolizidine alkaloids of food origin.

We report the occurrence of veno-occlusive disease in a preterm neonate who was symptomatic with hepatomegaly and ascites and was delivered by caesarean section for threatening fetal asphyxia and died shortly afterwards. Post mortem examination revealed veno-occlusive disease typical for pyrrolizidine alkaloid poisoning. The content of pyrrolizidine alkaloids in the liver could be confirmed. Analysis of a herbal mixture which was used for cooking in the family revealed high amounts of the respective alkaloids clarifying the source of the poison and the causal relationship.

Hypoglycemic effect of Cecropia obtusifolia on streptozotocin diabetic rats.

The hypoglycemic effects of water and butanolic extracts prepared from leaves of Cecropia obtusifolia (Cecropiaceae) were examined in streptozotocin induced diabetic rats. A single oral administration of a water extract at doses of 90 and 150 mg/kg and of a butanol extract at doses of 9 and 15 mg/kg significantly (P<0.05) lowered the plasma glucose levels in diabetic rats after 3 h administration. Glibenclamide was used as reference and showed similar hypoglycemic effect to the tested extracts at a dose of 3 mg/kg. The flavone, isoorientin and 3-caffeoylquinic acid (chlorogenic acid), were isolated as the important constituents of the plant and were identified as the main constituents in both extracts, too.

Pyrrolizidine alkaloids from Ageratum houstonianum Mill.

Four pyrrolizidine alkaloids (PA) were isolated from Ageratum houstonianum and their structures elucidated by spectroscopical methods. Besides the already known lycopsamine three new PA were found. Their structures are the 2S-2-hydroxy-2,3-dimethyl-butanoyl-O(9) as well as the O(7) esters of retronecine and the O(9) derivative of heliotridine.

Hypoglycemic effect of Equisetum myriochaetum aerial parts on streptozotocin diabetic rats.

The hypoglycemic effect of water as well as butanolic extracts prepared from aerial parts of Equisetum myriochaetum (Equisetaceae) was examined in streptozotocin induced diabetic rats. A single oral administration of the water extract (WE) at doses of 7 and 13 mg/kg and of the butanol extract (BE) at doses of 8 and 16 mg/kg significantly (P<0.001) lowered the plasma glucose levels in diabetic rats after three hours of the administration. As a reference drug glibenclamide was used and showed, at a dose of 3 mg/kg, similar hypoglycemic effect like the tested extracts. Three kaempferol glucosides and one caffeoyl glucoside were isolated from the drug and were shown to be the main constituents in both extracts.

Generation and characterization of monoclonal antibodies against the pyrrolizidine alkaloid retrorsine.

Monoclonal antibodies against retrorsine were established using a retrorsine-hemisuccinate::bovine-thyroglobuline conjugate as antigen for immunization. In competitive enzyme-linked immunoassays the specificity of the obtained antibodies was tested with 20 different pyrrolizidine alkaloids. Among these the alkaloids acetylgynuramine, gynuramine, integerrimine, neoplatyphylline, platyphylline, rosmarinine, senecionine, and seneciphylline were able to bind the antibody. There was no cross-reactivity with the alkaloids senkirkine, angeloyl-heliotridine, heliotridine, axillarine, anacrotine, monocrotaline, madurensine, otosenine, retronecine, tussilagine, triangularine, and jacoline as well as with seneciphylline N-oxide. From this antigen spectrum it can be concluded that besides the necic structure itself the dominant and discriminative epitope consists of the exocyclic ethylidene group of the various diesters.

Pyrrolizidine alkaloids from Eupatorium portoricense.

Three pyrrolizidine alkaloids were isolated from Eupatorium portoricense and their structures elucidated by spectroscopic methods as (-)-viridifloryl-supinidine (amabiline), (-)-viridifloryl-heliotridine (echinatine), and C12- O-acetyl-(-)-viridifloryl-heliotridine (O(12)-acetylechinatine).