Protective role of Cynara cardunculus L. leaf extract on gut barrier and inflammation: Insights from in vitro models.

Intestinal epithelial cells form a highly specialized barrier that protects the body from harmful substances present in the gut lumen through tight junctions (TJ), which connect adjacent cells, regulate paracellular transport, and maintain epithelial polarity. When TJ integrity is compromised, intestinal permeability increases, a condition commonly referred to as “leaky gut”. This phenomenon is frequently associated with gastrointestinal disorders such as inflammatory bowel disease (IBD), characterized by chronic immune-mediated inflammation and impaired intestinal function. Polyphenols, naturally occurring compounds in plants, have gained attention for their ability to support gut health by preserving barrier integrity and modulating inflammatory responses. In this context, the present study investigated the in vitro effects of a standardized polyphenol-rich extract obtained from Cynara cardunculus L. subsp. scolymus leaves (CCLE) on intestinal epithelial barrier function and acute inflammation induced by TNF-α in Caco-2 cells. Treatment with CCLE during cell differentiation improved barrier properties, as evidenced by increased transepithelial electrical resistance (TEER), reduced fluorescein permeability, and enhanced expression of TJ proteins (occludin, claudin-1, ZO-1). CCLE also accelerated TJ reassembly in the Ca²⁺ switch assay, effects linked to activation of the AMPK/SIRT1 signaling pathway. Furthermore, in the TNF-α-induced inflammation model, CCLE inhibited NF-κB activation, downregulated pro-inflammatory mediators (IL-8, COX-2), and reduced oxidative stress by stimulating the Nrf2 pathway, thereby improving cellular redox balance. Overall, these findings highlight the potential of CCLE to reinforce intestinal barrier integrity and counteract inflammatory damage. Considering that Cynara leaves are currently an agro-industrial byproduct, their valorization as a source of bioactive polyphenols represents a promising strategy for promoting gut health and supporting the prevention or management of IBD.