Carboxyatractyloside – the toxin produced by the common cockleburs

Xanthium, also known commonly as cocklebur, is a genus of flowering plants with several species distributed worldwide (Fig. 1,2). Cockleburs are usually found along the shores of streams and low-lying areas of fields. Cockleburs flower in July to October when days are getting shorter. It presents an invasive character and some species are distributed worldwide. One of the reason of cockleburs success is that seeds can remain dormant in the soil for periods of months or even years.

This weed is a widespread problem, invading agricultural land and poisoning livestock . In 1907 in Australia was reported the death of 700 cattle in a night after eating this poisonous plant. In Bangladesh after a monsoon period in 2008, it occurred a big outbreak of human poisoning after consumption of Xanthium strumarium. Due to the inaccessibility to food, people consumed the seedlings in large quantities. It resulted in the hospitalization of 76 persons, from which 25 died.

The reason behind the toxicity of the genus Xanthium is the diterpenoid glycoside Carboxyatractyloside (CAT) (Fig. 3). The plants presents high concentration of this toxin, specially in the seeds. CAT is highly toxic to animals as it inhibits mitochondrial oxidative phosphorylation, therefore affecting the ADP/ATP translocase. The toxic symptoms on humans after ingestion are abdominal pain, nausea, vomiting and drowsiness. CAT presents acute toxicity, with observed cases leading to necrosis, internal hemorrhage and multiple organ dysfunctions.

CAS NO: 33286-30-5
Canonical SMILES: CC(C)CC(=O)OC1C(C(C(OC1OC2CC3(C4CCC5CC4(CCC3C(C2)(C(=O)O)C(=O)O)C(C5=C)O)C)CO)OS(=O)(=O)O)OS(=O)(=O)O

References:

• Turgut, M., Alhan, C. C., Gürgöze, M., Kurt, A., Doğan, Y., Tekatli, M., ... & Aygün, A. D. (2005). Carboxyatractyloside poisoning in humans. Annals of tropical paediatrics, 25(2), 125-134.
• Gurley, E. S., Rahman, M., Hossain, M. J., Nahar, N., Faiz, M. A., Islam, N., ... & Islam, M. S. (2010). Fatal outbreak from consuming Xanthium strumarium seedlings during time of food scarcity in northeastern Bangladesh. PloS one, 5(3), e9756.
• Pebay-Peyroula, E., Dahout-Gonzalez, C., Kahn, R., Trézéguet, V., Lauquin, G. J. M., & Brandolin, G. (2003). Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature, 426(6962), 39.
  http://poisonousplants.ansci.cornell.edu/toxicagents/carglyco.html

Picture attributions:

• Cattle poisoning: https://commons.wikimedia.org/wiki/File:Cattle_poison.jpg
• Xanthium: https://en.wikipedia.org/wiki/Xanthium#/media/File:Xanthium_strumarium_L..jpg