Upcycled Green Coffee Phenolic‐Rich Extract Modulates Key Pathways of Glucose Absorption in Caco‐2 Cells: Findings From a Screening of Upcycled Agro‐Industrial By‐Products for Application in Functional Foods

While some purified phenolic compounds are known to modulate intestinal carbohydrate metabolism, the potential of complex phenolic-rich extracts from different agro-industrial by-product sources remains underexplored. This study evaluated extracts obtained from major Brazilian by-products as a sustainable strategy to recover different bioactive compounds with the potential to reduce the glycemic impact of sugars and promote metabolic health. Phenolic-rich extracts from green coffee (GCE), orange by-products (OBE), and peanut skin (PSE) were assessed for cytotoxicity potential, sucrase-isomaltase (SI) inhibition, basolateral glucose transport, gene expression of glucose transporters, and genes involved in glucose transporter 2 (GLUT2) translocation in Caco-2 cells. The extracts showed no cytotoxicity, except for PSE above 30 µg/mL. OBE and PSE were unable to inhibit SI, and PSE did not inhibit glucose transport and gene expression. GCE inhibited SI activity by up to 51% and achieved maximum inhibition at 100 µg/mL, with no further effect at 10-fold higher concentrations. Despite not reducing glucose transport, GCE downregulated SGLT-1 (0.35-fold) and PKC (0.37-fold), suggesting a modulatory effect on active glucose transport and possibly interference in GLUT2 translocation. These findings indicate the potential of GCE to modulate intestinal absorption of carbohydrates, making it promising for application in functional foods with possible regulation of the glycemic response.