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Screening botanical extracts for quinoid metabolites.
B M Johnson1, J L Bolton, R B van Breemen
1Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612-7231, USA.
Chemical Research in Toxicology
|November 20, 2001
Summary
A new in vitro assay screens botanical supplements for toxic compounds. This method detects reactive metabolites by identifying glutathione (GSH) adducts, aiding in preliminary safety assessments for dietary products.
Area of Science:
- Pharmacology
- Toxicology
- Analytical Chemistry
Background:
- Botanical dietary supplements are increasingly popular, yet lack mandatory safety assessments in the USA.
- Hepatic cytochromes P450 bioactivation can produce toxic quinoid species from botanical compounds.
- Glutathione (GSH) conjugation is a key in vivo detoxification pathway for reactive metabolites.
Purpose of the Study:
- To develop and validate an in vitro assay for screening botanical extracts.
- To detect the formation of potentially toxic electrophilic species upon metabolic activation.
- To assess the safety of botanical dietary supplements before human consumption.
Main Methods:
- Pulsed ultrafiltration coupled with liquid chromatography-tandem mass spectrometry (LC-MS-MS).
- Rat liver microsomes used for bioactivation of botanical compounds.
- Detection of stable GSH adducts formed by reactive metabolites.
Main Results:
- The assay successfully identified GSH adducts in extracts of sassafras, comfrey, and rosemary.
- No GSH adducts were detected in red clover extracts.
- Novel metabolites of rosmarinic acid forming GSH conjugates were identified.
Conclusions:
- The developed in vitro assay is effective for preliminary toxicity screening of botanical dietary supplements.
- Positive results indicate the need for further toxicological studies.
- This assay can contribute to ensuring the safety of botanical products.