Another Class of Plant Alkaloids

I’ve already described plants that accumulate alkaloids in their tissues in posts in the Plant category elsewhere in this site.  A group of alkaloids found in plants and toxic to humans- the pyrrolizidine alkaloids (PAs) are interesting, inter alia, because there is evidence of their occurrence in wild-collected plants that serve as precursors in the production of herbal medicines.  The PAs collectively comprise a group of around 100   alkaloid compounds that are still the subject of inquiry as to their toxicological  and in some cases, presumed salutary effects. Many PAs have been shown to be carcinogenic, tumorigenic, hepatototoxic and genotoxic in laboratory animal studies although the applicability of this work to human health is not yet fully resolved.

 PAs are found in thousands of species of higher plants, totaling perhaps 3% of all flowering plants, a number estimated to be just over 400,000 species (kew.org).  PAs are most commonly found in three large plant families- Boraginaceae, Asteraceae, and Fabaceae). There are over 6000 species in these families and about half or them have shown PA toxicity activity. There also are many orchid species containing PAs.

 It is suspected that PAs repel insects that otherwise would feed on the plant’s tissues and that natural selection may have favored species with the capacity to synthesize and store PAs as well as other alkaloids. As a possible example, petasitenine, a carcinogenic PA occurring in Farfugium japonicum (formerly Ligularia tussilaginia; see photograph) of the Asteraceae, has been chemically  isolated. (Niwa, H. et al. 1985). F. japonicum is an occasional garden plant in North America and a native forest understory species in Europe and temperate Asia. The scarcity of herbivore activity as seen in the nearly perfect leaves may be due to inhibition of herbivores by toxic PAs. However because the plant is not native to North America, it is possible that herbivores of the plant’s native habitat are absent from North America. The photograph was taken in late 2015 in central Florida after the plant spent the long hot summer outdoors where pesticides were avoided.

Potted Farfugium japonicum grown   in unsprayed yard in Florida. Note near total absence of herbivory.

Potted Farfugium japonicum grown in unsprayed yard in Florida. Note the near total absence of herbivory.

A  large number of  herbaceous species containing PAs are used for traditional Chinese medicines giving rise to concern that active therapeutic compounds may be tumorigenic or otherwise toxic to humans  ( Fu, P.P., et al. 2002), Many herbal or folk teas also contain PAs and large scale poisonings have been reported in several countries (not the US or in Europe). In addition, poisoning of livestock from eating plants containing PAs such as species of Crotolaria is reported to be widespread.

Flowering plant of Crotolaria spectabilis

Flowering plant of Crotolaria spectabilis. Also note immature pods.

 Some plants used as vegetables in Japan are known to contain PAs including  the aforementioned F. japonicum, plus Symphytum officinale (borage of the Boraginaceae), a common garden plant in North America. Borage is described by at least one American seed supply company as providing edible flowers and leaves. Other PA-containing species used locally as vegetables include  Senecio cannabifolius, and Petasites japonicus, both of the Asteraceae. The latter is distributed over a range similar to that of  F. japonicum.  

 The root extract of a second species of Petasites, P. hybridus, also PA-containing, is an ingredient in a commercially available headache remedy that can be ordered from US suppliers on the internet. Fortunately, where GMP (Good Manufacturing Practice) standards are followed, approved supplements are treated non-chemically to remove PAs from the root extract. It is therefore advisable if in the market for such supplements to determine if GMP guidelines have been followed.

  One study concluded that at least 49 species of herbal plants contained  PAs (Roeder 1995).  Most of  these species are sources for locally made teas in rural China rather than commercialized sources. But five species from this list are incorporated into the year 2000 edition of the China Pharmacopeia.

  A more recent study adds 11 additional species to the Roeder list  (Lin et al).  Among the over 90 PAs found in Chinese medicinal herbs, 19 were found to be tumorigenic in animals although this is a minimum as not all were subjected to animal testing. Although banned now, in the past in Europe, many herbs containing PAs were consumed by humans.

  Fernald et al. in their respected book, Edible Wild Plants of Eastern North America (Harper & Bros., 1958) considered coltsfoot (Tussilago farfara  from Eurasia and introduced into North America, as the source of a “delicious confection”, and noted that it was “famous as a supposed cough-medicine” (T.farfara  is almost certainly no longer a valid name and  the plants referred to may just be F.japonicum). The discovery of toxic PAs in this species has, however, given rise to liver health concerns. Fernald et al. (1958) also describe “sweet coltsfoot” (Petasites palmatus and P. vitifolius) as providing  a  “very good potherb”  (cooked greens) consistent with the similar use of Eurasian species of the genus.

 Medicinal practices based on species containing PAs are found in other countries as well such as Madagascar and the Mascarene Islands (Roeder, E.   and H. Wiedenfeld, 2011). The authors noted that many users of traditional medicines believe that they can be used without risk and side effects.

 References

Fernald, M. L., A. C. Kinsey and R.C. Rollins, 1958. Edible Wild Plants of Eastern North America (Harper & Brothers).

 Fu, P.P., et al. 2002, Journal of Food and Drug Analysis 10:198-211).

 Niwa, H. et al. 1985, Journal Natural Products 48(6):1003).

 Roeder 1995 Medicinal plants in Europe containing pyrrolizidine alkaloids.  Pharmazie. 50: 83-98). 

 Roeder, E.   and H. Wiedenfeld, 2011. Pyrrolizidine alkaloids in plants used in the traditional medicine of Madagascar and Mascarene Islands. Pharmazie 66:637).