Structural Impact of Steroidal Glycoalkaloids: Barrier Integrity, Permeability, Metabolism, and Uptake in Intestinal Cells

Abstract

ScopePotato tubers represent an essential food component all over the world and an important supplier of carbohydrates, fiber, and valuable proteins. However, besides their health promoting effects, potatoes contain α‐solanine and α‐chaconine, which are toxic steroidal glycoalkaloids (SGAs). Other solanaceous plants like eggplants and tomatoes produce SGAs as well, different in their chemical structure. This study aims to investigate toxic effects (cholinesterase inhibition, membrane, and barrier disruption), permeability, metabolism, and structure–activity relationships of SGAs.Methods and resultsα‐solanine, α‐chaconine, α‐solasonine, α‐solamargine, α‐tomatine, and their respective aglycones solanidine, solasodine, and tomatidine are analyzed using Ellman assay, cellular impedance spectroscopy, cell extraction, and Caco‐2 intestinal model. Additionally, metabolism is analyzed by HPLC‐MS techniques. The study observes dependencies of barrier disrupting potential and cellular uptake on the carbohydrate moiety of SGAs, while permeability and acetylcholinesterase (AChE) inhibition are dominated by the steroid backbone. SGAs show low permeabilities across Caco‐2 monolayers in subtoxic concentrations. In contrast, their respective aglycones reveal higher permeabilities, but are extensively metabolized.ConclusionBesides structure–activity relationships, this study provides new information on the overall effects of steroidal alkaloids on intestinal cells and closes a gap of knowledge for the metabolic pathway from oral uptake to final excretion.