Pyrrolizidine alkaloid

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.[1] 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.[2] Honey can contain pyrrolizidine alkaloids,[3][4] as can grains, milk, offal and eggs.[5] To date (2011), there is no international regulation of PAs in food, unlike those for herbs and medicines.[6][7]

Skeletal formula of retronecine, a pyrrolizidine alkaloid found in the Common groundsel (Senecio vulgaris) and comfrey (Symphytum spp.)

Unsaturated pyrrolizidine alkaloids are hepatotoxic, that is, damaging to the liver.[8][9] PAs also cause hepatic veno-occlusive disease and liver cancer.[10] PAs are tumorigenic.[11] 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.[11]

Some ruminant animals, for example cattle, showed no change in liver enzyme activities or any clinical signs of poisoning when fed plants containing pyrrolizidine alkaloids.[12] Yet Australian studies have demonstrated toxicity[13] Sheep, goats and cattle are much more resistant and tolerate much higher PA dosages, thought to be due to thorough detoxification via PA-destroying rumen microbes.[14] Males react more sensitively than females and fetuses and children.[15]

PA is also used as a defense mechanism for 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.[16]

Ecology
Main article: Pyrrolizidine alkaloid sequestration

Many plants contain pyrrolizidine alkaloids, and in turn there are many insects which consume the plants and build up the alkaloids in their bodies.[17] For example, male queen butterflies utilize pyrrolizidine alkaloids to produce pheromones useful for mating.[18] The butterfly Danaus chrysippus is known to obtain pyrrolizidine alkaloids in their diet and store these chemicals, making them toxic and unpalatable to predators.[19] 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).[20]

Plants species containing pyrrolizidine alkaloids
This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.

The effect of PAs in humans, that is PAILDs,[28] 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.

  • Platynecine
  • Heliotridine
  • Retronecine

The three largest groups are based on the three necine bases platynecine, heliotridine and retronecine.


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References
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  3. Kempf, M; Reinhard, A; Beuerle, T (Jan 2010). "Pyrrolizidine alkaloids (PAs) in honey and pollen-legal regulation of PA levels in food and animal feed required". Mol Nutr Food Res. 54 (1): 158–68. doi:10.1002/mnfr.200900529. PMID 20013889.
  4. Edgar, John A.; Roeder, Erhard; Molyneux, Russell J. (2002). "Honey from Plants Containing Pyrrolizidine Alkaloids: A Potential Threat to Health". J. Agric. Food Chem. 50 (10): 2719–2730. doi:10.1021/jf0114482. PMID 11982390.
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  7. German Commission E monographs
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  9. Schoental, R.; Kelly, JS (April 1959). "Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, lasiocarpine and retrorsine". The Journal of Pathology and Bacteriology. 77 (2): 485–495. doi:10.1002/path.1700770220. PMID 13642195.
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23. https://www.cdc.gov/nceh/stories/Ethiopia.html, Investigating Liver disease in Ethiopia

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