Phenolic-Rich Lentil Extracts Regulate Cytokine Production, Metabolic Pathways and Barrier Function in Intestinal...

Phenolic compounds are recognized for antioxidant, anti-inflammatory, and antidiabetic properties. Lentils are abundant in these compounds, yet comparative studies across varieties and intestinal cells effects remain limited. This study evaluated the nutritional composition, phenolic profile, antioxidant activity, and α-glucosidase inhibition of four lentil types in raw and cooked forms. L01 had the highest bioactive potential and was the only one selected for further evaluation in Caco-2 cells under basal and IL-1β-stimulated conditions. Cooking altered composition, leading to higher protein, fiber, and carbohydrates, reducing tannins, and maintaining high phytic acid in some varieties. L01 consistently showed the highest phenolic content, antioxidant activity, and enzyme inhibition. Its phenolic profile was dominated by kaempferol derivatives, (epi)catechin, and procyanidins, with cooking increasing monomeric catechins but reducing procyanidin oligomers. At noncytotoxic levels, L01 extracts reduced IL-6/8 secretion in stimulated cells, with stronger effects from raw extracts. Additionally, they decreased expression of inflammatory markers (IL-6/8/1β) while increasing expression of metabolic regulation- and barrier-related genes (Peroxisome proliferator-activated receptor-γ, Sirtuin 1, Occludin, and Cadherin-1). Only raw extracts significantly enhanced Heme oxygenase-1 expression under stimulation. These findings highlight compositional differences beyond tegument color and support further investigation of phenolic-rich lentils as potential functional food ingredients targeting gut and metabolic health.