Novel insights into enzymes inhibitory responses and metabolomic profile of supercritical fluid extract from chestnut shells upon intestinal permeability Pinto, Diana Lozano Castellón, Julián Silva, Ana Margarida Cádiz Gurrea, María de la Luz Segura Carretero, Antonio Lamuela-Raventós, Rosa María Vallverdú Queralt, Anna Delerue Matos, Cristina Rodrigues, Francisca Castanea sativa Phenolic compounds Supercritical fluid extraction The health benefits of chestnut (Castanea sativa) shells (CSs) have been ascribed to phytochemicals, mainly phenolic compounds. Nevertheless, an exhaustive assessment of their intestinal absorption is vital considering a possible nutraceutical application. This study evaluated the bioactivity of CSs extract prepared by Supercritical Fluid Extraction and untargeted metabolomic profile upon in-vitro intestinal permeation across a Caco-2/HT29- MTX co-culture model. The results demonstrated the neuroprotective, hypoglycemic, and hypolipidemic properties of CSs extract by inhibition of acetylcholinesterase, α-amylase, and lipase activities. The untargeted metabolic profiling by LC-ESI-LTQ-Orbitrap-MS unveiled almost 60 % of lipids and 30 % of phenolic compounds, with 29 metabolic pathways indicated by enrichment analysis. Among phenolics, mostly phenolic acids, flavonoids, and coumarins permeated the intestinal barrier with most metabolites arising from phase I reactions (reduction, hydrolysis, and hydrogenation) and a minor fraction from phase II reactions (methylation). The permeation rates enhanced in the following order: ellagic acid < o-coumaric acid < p-coumaric acid < ferulaldehyde ≤ hydroxyferulic acid ≤ dihydroferulic acid < ferulic acid < trans-caffeic acid < trans-cinnamic acid < dihydrocaffeic acid, with better outcomes for 1000 μg/mL of extract concentration and after 4 h of permeation. Taken together, these findings sustained a considerable in-vitro intestinal absorption of phenolic compounds from CSs extract, enabling them to reach target sites and exert their biological effects. 2024-04-10T08:23:16Z 2024-04-10T08:23:16Z 2024 journal article Food Research International 175 (2024) 113807 [10.1016/j.foodres.2023.113807] https://hdl.handle.net/10481/90578 10.1016/j.foodres.2023.113807 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Elsevier