Plant extracts identified by in vitro high-content screening improve epithelial barrier function and attenuate oxidative and inflammatory stress

Maintaining intestinal barrier integrity is crucial for gastrointestinal health. Bioactive compounds of plant origin can contribute to prevent barrier dysfunction. In this study, we employed a holistic approach to identify plant extracts with barrier improving properties utilizing a broad range of cell lines, epithelial models and assays targeting barrier protection, antioxidant activity, cytokine response and tight junction regulation. Among the 210 plant extracts screened from an in-house library, 5 % increased the transepithelial electrical resistance in MDCK-II cells. Subsequent validation in Caco-2 cells narrowed the number to 6 potent candidates. Among these, Lamium galebdolon , Anthriscus sylvestris and Asparagus officinalis exhibited the strongest barrier improvement through modulating the expression of CLDN1, CLDN3, OCLN and ZO-1. Furthermore, a combination of selected plant extracts delivered enhanced barrier tightness with clear additive effects exceeding those of the single extracts. Beyond this, the botanical mixture exhibited additive antioxidant, superior anti-inflammatory and barrier protective effects also under stress conditions. In conclusion, a tailored combination of selected plant extracts was identified that could be used in nutraceuticals to support gastrointestinal health.