Pinto, DianaLozano-Castellón, JuliánSilva, Ana MargaridaCádiz-Gurrea, María de la LuzSegura-Carretero, AntonioLamuela Raventós, Rosa Ma.Vallverdú i Queralt, AnnaDelerue-Matos, CristinaRodrigues, Francesca2024-02-292024-02-292023-12-020963-9969https://hdl.handle.net/2445/208223The 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.  1 p.application/pdfengcc-by-nc-nd (c) Diana Pinto, et al., 2023http://creativecommons.org/licenses/by-nc-nd/4.0/MetabolòmicaPolifenolsMetabolomicsPolyphenolsNovel insights into enzymes inhibitory responses and metabolomic profile of supercritical fluid extract from chestnut shells upon intestinal permeabilityinfo:eu-repo/semantics/article7414152024-02-29info:eu-repo/semantics/openAccess