Isolation of the major component in white snakeroot that is toxic after microsomal activation: Possible explanation of sporadic toxicity of white snakeroot plants and extracts

Abstract

Tremetone, the major toxic component in white snakeroot (Eupatorium rugosum Houtt) extracts, was isolated following an in vitro bioactivity assay. Microsomal activation was required to produce a product toxic to murine melanoma (B16F1) cells as well as five other mammalian cell cultures. The metabolic activation product(s) of tremetone is suspected to be responsible for the toxic activity of the plant. Tremetone is also smoothly converted to dehydrotremetone in the plant and cell free homogenates, and readily decomposes to dehydrotremetone in extracts. Dehydrotremetone is not toxic even after microsomal activation. The efficient conversion of tremetone to dehydrotremetone may explain why white snakeroot plant material and extracts have varied activities, and why a previous claim that tremetone was responsible for the toxic activity of white snakeroot was withdrawn. Rayless goldenrod extracts show the same toxic activity as white snakeroot and the toxic activity of rayless goldenrod is most likely due to tremetone.

Experimental Rayless Goldenrod (Isocoma pluriflora) Toxicosis in Goats

“…A previous study demonstrated that in vitro microsome-activated tremetone is cytotoxic, but dehydrotremetone was not. 2,3 This suggests that an ''activated'' tremetone metabolite is responsible for white snakeroot toxicity. However, this has not been confirmed experimentally.…”

“…4,10 Various toxins have been described in rayless goldenrod. 3,5,6,9,16 In addition to the previously mentioned tremetol, 5,6 several monoterpenes, sesquiterpenes, 16 and essential oils 3 have also been described. In vitro studies using a tremetol mixture suggests that at least 1 component of this mixture or of its metabolites inhibits oxidative phosphorylation, most likely by inhibiting the tricarboxylic acid cycle.…”

Evaluation of Drying Methods and Toxicity of Rayless Goldenrod (Isocoma pluriflora) and White Snakeroot (Ageratina altissima) in Goats

“…The conversion of toxic tremetone (1) to nontoxic dehydrotremetone (2) was offered as an explanation for the sporadic toxicity of white snakeroot and rayless goldenrod. 10,11 In general, subsequent review literature on white snakeroot toxicity has perpetuated these reports and their suppositions: tremetol or tremetone (1) are the toxic principles; white snakeroot plants lose toxicity when dried; 12−15 and tremetone (1) is converted to dehydrotremetone (2) during isolation. 13 Additionally, it is reported that rayless goldenrod contains the same or similar toxic principle as white snakeroot.…”

White Snakeroot [Ageratina altissima(L.) King & H.E. Robins]

“…11 In plants, tremetone is converted to dehydrotremetone, but these microsomal activation studies suggest that dehydrotremetone is not physiologically active. 11 In plants, tremetone is converted to dehydrotremetone, but these microsomal activation studies suggest that dehydrotremetone is not physiologically active.…”