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

SCOPE: Potato 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 RESULTS: α-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. CONCLUSION: Besides 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.

Intestinal Metabolism of Selected Steroidal Glycoalkaloids in the Pig Cecum Model.

Due to the presence of the steroidal glycoalkaloid solanine, the potato was chosen as Germany's poisonous plant of the year 2022. Steroidal glycoalkaloids are secondary plant metabolites which have been reported to induce toxic as well as beneficial health effects. Nevertheless, data regarding occurrence, toxicokinetics, and metabolism of steroidal glycoalkaloids is scarce, and substantially more research is required for a proper risk assessment. Therefore, the intestinal metabolism of solanine, chaconine, solasonine, solamargine, and tomatine was investigated using the ex vivo pig cecum model. All steroidal glycoalkaloids were degraded by the porcine intestinal microbiota, releasing the respective aglycon. Furthermore, the hydrolysis rate was strongly dependent on the linked carbohydrate side chain. Solanine and solasonine, which are linked to a solatriose, were metabolized significantly faster than the chaconine and solamargin, which are linked to a chacotriose. In addition, stepwise cleavage of the carbohydrate side chain and the formation of ß- and γ-intermediates were detected by HPLC-HRMS. The results provide valuable insights into the intestinal metabolism of selected steroidal glycoalkaloids and help to reduce uncertainties and improve risk assessment.

Release of Small Phenolic Metabolites from Isotopically Labeled 13C Lignin in the Pig Cecum Model.

A diet with a high dietary fiber content is often recommended in today's nutrition due to several beneficial health effects related to its intake. Lignin as a part of dietary fiber is the second most abundant natural polymer and considered to be stable during digestion. However, some studies indicate a partial degradation during the intestinal metabolism. To further elucidate this hypothesis, the aim of this study was to investigate whether lignin is metabolized by the gut microbiota using the ex vivo pig cecum model. As potential lignin-derived metabolites might already naturally occur in the pig cecal matrix, an approach using isotopically labeled 13C lignin was chosen for this study. Ten small phenolic lignin degradation products and their time-dependent metabolism were identified via an untargeted HPLC-HRMS approach, and the quantity of the metabolites was estimated. From the results, we conclude that lignin is partially degraded releasing small phenolic metabolites.

Intestinal Absorption and Metabolism of the Tomato Imidazole Alkaloids N-Caprylhistamine-ß-glucoside and N-Caprylhistamine.

Histamine-based imidazole alkaloids N-caprylhistamine (HmC8) and N-caprylhistamine-ß-glucoside (HmC8-Glc) were recently identified as precursors for a tomato biomarker. As studies regarding metabolism and bioavailability are scarce, the present study aimed at the elucidation of intestinal absorption and metabolism using the Caco-2 model and the pig cecum model to mimic human intestinal conditions. The most abundant imidazole alkaloid HmC8-Glc was neither absorbed nor transferred across cellular barriers but extensively metabolized to HmC8 in the pig cecum model, whereas the aglycon HmC8 is subjected to transport and metabolic processes through the Caco-2 monolayer and metabolized to the bioactive neurotransmitter histamine by the intestinal microbiota. Deduced from the combined results of both methods, HmC8-Glc is not absorbed directly via the intestinal epithelium but requires a metabolic cleavage of the glycosidic bond by the gut microbiota. Because of the high bioavailability of the released HmC8 and histamine, HmC8 and its glucoside might also be involved in the intolerance to tomato products by histamine-intolerant consumers.

Intestinal Metabolism of α- and ß-Glucosylated Modified Mycotoxins T-2 and HT-2 Toxin in the Pig Cecum Model.

The type A trichothecene mycotoxins T-2 and HT-2 toxin are fungal secondary metabolites produced by Fusarium fungi, which contaminate food and feed worldwide. Especially as a result of the high toxicity of T-2 toxin and their occurrence together with glucosylated forms in cereal crops, these mycotoxins are of human health concern. Particularly, it is unknown whether and how these modified mycotoxins are metabolized in the gastrointestinal tract and, thus, contribute to the overall toxicity. Therefore, the comparative intestinal metabolism of T-2 and HT-2 toxin glucosides in α and ß configuration was investigated using the ex vivo pig cecum model, which mimics the human intestinal metabolism. Regardless of its configuration, the C-3 glycosidic bond was hydrolyzed within 10-20 min, releasing T-2 and HT-2 toxin, which were further metabolized to HT-2 toxin and T-2 triol, respectively. We conclude that T-2 and HT-2 toxin should be evaluated together with their modified forms for risk assessment.