Abstract
Minthostachys verticillata (Griseb.) Epling, commonly known as peperina, is an aromatic species endemic to Argentina and traditionally used for gastrointestinal ailments. Despite its extensive folkloric use and inclusion in the Argentine Pharmacopoeia, its aqueous extract (the most commonly consumed preparation) has been described in terms of major phytochemical groups, and, currently, no studies have investigated its effects on key intestinal epithelial mechanisms. This plant is also employed in the production of beverages and herbal blends, and its massive consumption highlights the importance of its scientific study. Here, the aqueous extract of M. verticillata was characterized by liquid chromatography-tandem mass spectrometry, leading to the identification of fourteen polyphenolic compounds. In intestinal cell models, the extract displayed high IC(50) values, supporting its safety, and exhibited concentration-dependent bioactivity. In HT-29 cells, it modulated NF-κB activation induced by TNF-α and reduced LPS-stimulated IL-8 production. Pretreatment of Caco-2 monolayers prevented the decrease in transepithelial electrical resistance, increased FITC-dextran permeability, and nitric oxide production triggered by an inflammatory cocktail. Additionally, the extract inhibited HT-29 cell migration. These results demonstrate that M. verticillata aqueous extract exerts anti-inflammatory, barrier-protective, and anti-migratory effects in vitro, providing novel insights into how its polyphenolic composition may underlie these biological activities, supporting its traditional use and potential applications in intestinal health.