pyrrolizidine alkaloids

Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Pyrrolizidine alkaloids are produced by plants as a defense mechanism against insect herbivores. More than 660 PAs and PA N-oxides have been identified in over 6,000 plants, and about half of them exhibit hepatotoxicity. They are found frequently in plants in the Boraginaceae, Asteraceae, Orchidaceae and Fabaceae families; less frequently in the Convolvulaceae and Poaceae, and in at least one species in the Lamiaceae.
It has been estimated that 3% of the world’s flowering plants contain pyrrolizidine alkaloids. Honey can contain pyrrolizidine alkaloids, as can grains, milk, offal and eggs. To date (2011), there is no international regulation of PAs in food, unlike those for herbs and medicines.

Unsaturated pyrrolizidine alkaloids are hepatotoxic, that is, damaging to the liver. PAs also cause hepatic veno-occlusive disease and liver cancer. PAs are tumorigenic. Disease associated with consumption of PAs is known as pyrrolizidine alkaloidosis.

Of concern is the health risk associated with the use of medicinal herbs that contain PAs, notably borage leaf, comfrey and coltsfoot in the West, and some Chinese medicinal herbs.

Some ruminant animals, for example cattle, show no change in liver enzyme activities or any clinical signs of poisoning when fed low concentrations of plants containing pyrrolizidine alkaloids. Yet, Australian studies have demonstrated toxicity. Sheep and goats especially, and to a lesser degree cattle, are much more resistant and tolerate much higher PA dosages, thought to be due to thorough detoxification via PA-destroying rumen microbes. Males react more sensitively than females, fetuses, and children.

PA is also used as a defense mechanism by some organisms such as ''Utetheisa ornatrix''. ''Utetheisa ornatrix'' caterpillars obtain these toxins from their food plants and use them as a deterrent for predators. PAs protect them from most of their natural enemies. The toxins stay in these organisms even when they metamorphose into adult moths, continuing to protect them throughout their adult stage.

Ecology

Many plants contain pyrrolizidine alkaloids, and in turn there are many insects which consume the plants and build up the alkaloids in their bodies. For example, male queen butterflies utilize pyrrolizidine alkaloids to produce pheromones useful for mating. The butterfly ''Danaus chrysippus'' is known to obtain pyrrolizidine alkaloids in their diet and store these chemicals, making them toxic and unpalatable to predators. ''Greta oto'', the glasswing butterfly, uses pyrrolizidine alkaloids for both toxicity in the adult moth and pheromone production in the male butterfly. The garden tiger moth also stores these compounds as a caterpillar, using them for larval (through the use of spines) and adult defense (in the form of a spray and bad taste).

Plants species containing pyrrolizidine alkaloids

* ''Adenostyles alliariae''
* '' Adenostyles glabra''
* ''Ageratum conyzoides''
* '' Ageratum houstonianum''
* ''Anchusa officinalis''
* '' Arnebia euchroma''
* ''Borago officinalis'' (< 10 ppm, non-toxic)
* '' Cacalia hastata''
* '' Cacalia hupehensis''
* ''Chromolaena odorata''
* ''Cordia myxa''
* ''Crassocephalum crepidioides''
* '' Crotalaria albida''
* '' Crotalaria assamica''
* '' Crotalaria crispat''
* '' Crotalaria dura''
* '' Crotalaria globifera''
* ''Crotalaria mucronata''
* ''Crotalaria sesseliflora''
* '' Crotalaria spectabilis''
* '' Crotalaria tetragona''
* ''Crotalaria retusa''
* '' Cynoglossum amabile''
* '' Cynoglossum lanceolatum''
* ''Cynoglossum officinale''
* '' Cynoglossum zeylanicum''
* ''Echium plantagineum''
* ''Echium vulgare''
* '' Emilia sonchifolia''
* ''Eupatorium cannabinum''
* '' Eupatorium chinense''
* '' Eupatorium fortunei''
* '' Eupatorium japonicum''
* ''Eupatorium perfoliatum''
* '' Eupatorium purpureum''
* '' Farfugium japonicum''
* ''Gynura bicolor''
* '' Gynura divaricata''
* '' Gynura segetum''
* '' Heliotropium amplexicaule''
* ''Heliotropium europaeum''
* '' Heliotropium indicum''
* ''Heliotropium popovii''
* '' Lappula intermedia''
* '' Ligularia cymbulifera''
* '' Ligularia dentata''
* '' Ligularia duiformis''
* '' Ligularia heterophylla''
* '' Ligularia hodgsonii''
* '' Ligularia intermedia''
* '' Ligularia lapathifolia''
* '' Ligularia lidjiangensis''
* '' Ligularia platyglossa''
* '' Ligularia tongolensis''
* '' Ligularia tsanchanensis''
* '' Ligularia vellerea''
* '' Liparis nervosa''
* ''Lithospermum erythrorhizon''
* ''Neurolaena lobata''
* ''Petasites japonicus''
* '' Senecio alpinus''
* '' Senecio argunensis''
* ''Senecio brasiliensis''
* ''Senecio chrysanthemoides''
* '' Senecio cineraria''
* '' Senecio glabellus''
* '' Senecio integrifolius var. fauriri''
* '' Senecio interggerrimus''
* ''Senecio jacobaea''
* ''Senecio lautus''
* '' Senecio linearifolius''
* ''Senecio madagascariensis''
* '' Senecio nemorensis''
* '' Senecio quadridentatus''
* '' Senecio riddelli''
* '' Senecio scandens''
* ''Senecio vulgaris''
* '' Syneilesis aconitifolia''
* ''Symphytum officinale''
* ''Tussilago farfara''

The effect of PAs in humans, that is PAILDs (Pyrrolizidine Alkaloid Induced Liver Diseases), of epidemic proportions was recorded after a long field-level epidemiological investigation in the northern region of Ethiopia-Tigray.

Classification

One classification is based on the substitution pattern of the pyrrolizidine ring. This part of the structure is normally referred to as necine bases. The three largest groups are based on the three necine bases platynecine, heliotridine and retronecine.

File:Platynecine.png, Platynecine
File:Heliotridine.png, Heliotridine
File:Retronecine.svg, Retronecine

References

External links

*
*{{cite journal , url=http://www.henriettes-herb.com/PAs/PAs.html , title=Medicinal plants in Europe containing pyrrolizidine alkaloids , author=E. Röder , journal= Die Pharmazie , year=1995 , volume=50 , pages=83–98
Retronecine
at KEGG
msn.com/de News Report: Well-known brands affected: This is how much poison there is in these herbal and chamomile teas. 6 out of 13 brands of herbal tea available in Germany contain the poison.

Plant toxins

Hepatotoxins