Integrated Molecular and Functional Analysis of Hop Ethanolic Extract in Caco-2 Cells: Insights into Inflammation, Barrier Function, and Transport.

Hop (Humulus lupulus L.) is a well-known medicinal and brewing plant, yet studies on the biological activity of its complete extracts remain limited. A comprehensive characterization of a full hop ethanolic extract (HLE) was conducted, integrating untargeted HPLC-MS profiling, anti-inflammatory evaluation in an inflammation-induced Caco-2 model, and transport assessment across intestinal epithelial monolayers. After ultrafiltration to remove pyrogenic components, HLE reduced IL-6 secretion in a concentration-dependent manner and decreased IL-8 levels, while mitigating IL-1β-induced barrier disruption as reflected by TEER recovery. HPLC-MS analysis of the basolateral compartment revealed selective permeability of medium-sized bitter-acid derivatives and the presence of three features not detected in the original extract, suggesting metabolic transformation during epithelial passage. Overall, the complete extract exhibited moderate but biologically relevant anti-inflammatory and barrier-protective effects in intestinal epithelial cells. The use of the whole extract, without isolating individual fractions, represents a practical and physiologically meaningful approach that may facilitate its application in the formulation of functional foods or dietary supplements.