Identification of the toxic components in white snakeroot (Ageratina altissima)

Authors: Davis, Thomas - Zane; Lee, Stephen; COLLETT, MARK - Massey University; Stegelmeier, Bryan; Green, Benedict - Ben; Grum, Daniel

Submitted to: International Symposium on Poisonous Plants
Publication Type: Proceedings
Publication Acceptance Date: 5/30/2015
Publication Date: 6/5/2015
Citation: Davis, T.Z., Lee, S.T., Collett, M.G., Stegelmeier, B.L., Green, B.T., Grum, D.S. 2015. Identification of the toxic components in white snakeroot (Ageratina altissima). International Symposium on Poisonous Plants. 9:194-200.

Interpretive Summary: White snakeroot poisoning causes “trembles” in livestock and “milk sickness” in humans that drink contaminated milk. Although a toxic extract from the plant was shown to cause the disease in the late 1920s, it was also later demonstrated that the extract was a mixture of many different compounds. It is widely believed that tremetone, which is part of the mixture, is the toxin. However, researchers have been unable to definitively demonstrate that tremetone is the toxic compound in white snakeroot. In attempt to correlate poisoning with tremetone concentrations, various plant populations with differing amounts of tremetone were dosed to Spanish Goats. Additionally extracts from white snakeroot were dosed using the same Spanish Goat model. The results demonstrated that there was not a correlation between tremetone concentrations and the relative toxicity of the different plant population, nor did tremetone-containing extracts cause the same lesions and disease as dried white snakeroot. These results indicate that it is likely that there is an additional compound in white snakeroot that causes toxicosis or acts synergistically with the benzofuran ketone compounds to produce the disease.

Technical Abstract: White snakeroot poisoning causes “trembles” in livestock that eat the plant, and “milk sickness” in nursing neonates and humans who drink contaminated milk. In the early 1900s the toxin was identified as tremetol that was later shown to be a mixture of several benzofuran ketone compounds including tremetone, dehydrotremetone, 6-hydroxytremetone and other lipophilic uncharacterized compounds. Recent research has focused on identifying the toxic component of the tremetol mixture. Plant populations with different chemical profiles were analyzed for their ability to cause “trembles” using a previously developed Spanish Goat model. Each plant population that caused toxicity contained a significant concentration (> 0.8 mg/g plant) of tremetone, however toxicity did not correlate well with the tremetone, 6-hydroxytremetone, or total benzofuran ketone concentrations as the animals had variable responses to the different plant populations. However, there was a correlation with dehydrotremetone that may account for part of the poisoning. In a following study, extracts from a white snakeroot collection that was very toxic in the goat model were tested for their ability to cause the disease in the same model. Extracts that contained the same concentrations of tremetone and the other benzofuran ketones as the dosed white snakeroot plant material did not cause the same serum biochemical and histopathological changes as the white snakeroot plant when dosed by oral gavage. These results suggest that there is an additional toxic component or synergistic action of another toxin with the benzofuran ketones that is not yet identified and needs to be elucidated by dosing extracts using the goat model or a small animal model.