Potentially toxic pyrrolizidine alkaloids in Eupatorium perfoliatum and three related species. Implications for herbal use as boneset

Authors: Colegate, Steven; UPTON, ROY - American Herbal Pharmacop; Gardner, Dale; Panter, Kip; BETZ, JOSEPH - National Institutes Of Health (NIH)

Submitted to: Phytochemical Analysis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2018
Publication Date: 7/2/2018
Citation: Colegate, S.M., Upton, R., Gardner, D.R., Panter, K.E., Betz, J.M. 2018. Potentially toxic pyrrolizidine alkaloids in Eupatorium perfoliatum and three related species. Implications for herbal use as boneset. Phytochemical Analysis. 29(6):613-626. https://doi.org/10.1002/pca.2775.
DOI: https://doi.org/10.1002/pca.2775

Interpretive Summary: Boneset (Eupatorium perfoliatum) is a herb with a long history of medicinal use. Recently it has been questioned rather boneset might contain potentially toxic compounds known as pyrrolizidine alkaloids. Pyrrolizidine alkaloids are well known to be hepato- or pneumotoxic and there is international concern about the presence of these compounds in foods, herbal medicines and dietary supplements from either natural or contaminated sources. Chemical analysis of 49 boneset samples confirmed the presence of potentially toxic dehydropyrrolizidine alkaloids (0.0002 – 0.07%, w/w) dominated by the pyrrolizidine alkaloid known as lycopsamine along with numerous related compounds. In addition, alcoholic tinctures and hot water infusions and decoctions made from pyrrolizidine alkaloid containing boneset had high concentrations of the alkaloids. Concerns associated with dehydropyrrolizidine alkaloids provide a compelling reason for preclusive caution until further research can better define the toxicity and carcinogenicity of the dehydropyrrolizidine alkaloid content of boneset.

Technical Abstract: Introduction — Pro-toxic dehydropyrrolizidine alkaloids are associated with liver disease in humans. Internationally, the potential for long-term, low-level or intermittent exposures to cause or contribute to chronically-developing diseases is of concern. Eupatorium perfoliatum is a medicinal herb referred to as boneset. While the presence of dehydropyrrolizidine alkaloids in some Eupatorium species is well-established, reports on Eupatorium perfoliatum are scant and contradictory. Objective — To investigate the presence of dehydropyrrolizidine alkaloids in a survey of boneset samples and related alcoholic tinctures, and hot water infusions and decoctions. Methods —Methanol, hot water or aqueous ethanol extracts of Eupatorium perfoliatum and three closely-related species were subjected to HPLC-esi(+)MS and MS/MS analysis using three complementary column methods. Dehydropyrrolizidine alkaloids were identified from their MS data and comparison with standards. Results — Forty-nine samples of Eupatorium perfoliatum were shown to contain dehydropyrrolizidine alkaloids (0.0002 – 0.07% w/w), the majority dominated by lycopsamine and intermedine, their N-oxides and acetylated derivatives. Alcoholic tinctures and hot water infusions and decoctions had high concentrations of the alkaloids. Different chemotypes, hybridization or contamination of some E. perfoliatum samples with related species were suggested by the co-presence of retronecine- and heliotridine-based alkaloids. Conclusions — Sampling issues, low and high alkaloid chemotypes of Eupatorium perfoliatum or interspecies hybridization could cause the wide variation in dehydropyrrolizidine alkaloid concentrations or the different profiles observed. Concerns associated with dehydropyrrolizidine alkaloids provide a compelling reason for preclusive caution until further research can better define the toxicity and carcinogenicity of the dehydropyrrolizidine alkaloid content of Eupatorium perfoliatum.