A comprehensive study on the digestion, absorption, and metabolization of tropane alkaloids in human cell models

Tropane alkaloids (TAs) are toxic compounds with potent anticholinergic effects. Herbal infusions are among the most contaminated food commodities; however, the fate of TAs after ingestion remains poorly understood. This study presents a comprehensive investigation into the absorption, and metabolism of five TAs (atropine, scopolamine, tropine, homatropine, and apoatropine) following the digestion of contaminated tea. In vitro human cell models were employed, including gastric (NCI-N87), intestinal (Caco-2:HT29-MTX), and hepatic (HEP-G2) cells. TAs were found to be highly absorbed in the intestinal epithelium, while gastric cells exhibited poor absorption. Metabolism was studied using a custom-made database, revealing that it occurs predominantly in intestinal cells, involving hydroxylation and methylation reactions. Cell metabolomics was conducted using annotation, fragment simulation, and statistical software platforms. Significant statistical differences were observed for 40 tentatively identified compounds. MetaboAnalyst 5.0 was employed to discern the most disturbed metabolic pathways, with amoniacids biosynthesis pathways and TCA cycles being the most affected. These pathways are involved in responses to cellular metabolic stress, neurotransmitter production, cellular energy generation, and the regulation of oxidative stress response. The findings of this study enhance our understanding of the fate of TAs after ingestion, their metabolization and their effects at the cellular level.