Nutraceutical potential of Echinacea purpurea (L.) Moench root extract for intestinal health: role of Nrf2-mediated antioxidant and cytoprotective pathways

Echinacea purpurea (L.) Moench Echinacea purpurea (L.) Moench is renowned for its immunomodulatory and anti-inflammatory properties, attributed to bioactive polyphenols, caffeic acid derivatives, and alkamides. This study aimed to evaluate the cytoprotective activity of an ethanolic extract from a mountain variety of E. purpurea root (ERes), cultivated in the Chiese Valley (Trentino, Italy), using gastrointestinal cell models. The research focused on the extract ability to modulate oxidative stress and activate cytoprotective pathways, specifically the Nrf2 signaling axis. Experiments were conducted on Caco-2 colon adenocarcinoma cells to assess epithelial barrier integrity and tolerability, and on H69 intrahepatic human cholangiocytes as a non-tumorigenic model to investigate antioxidant responses under pro-oxidant and inflammatory challenges. Cell-free assays confirmed ERes’s potent antioxidant capacity, showing marked DPPH and ABTS radical scavenging and significant metal-chelating activity. In vitro, ERes was non-cytotoxic and did not increase baseline ROS. Under tert-butyl hydroperoxide (tBOOH)-induced stress, ERes significantly restored cell viability and suppressed ROS production, with more pronounced effects in H69 cells. In an IL-6-induced inflammatory model, ERes mitigated oxidative damage and enhanced survival, comparable to N-acetylcysteine. Furthermore, ERes slightly increased transepithelial electrical resistance (TEER) in Caco-2 monolayers, suggesting improved barrier integrity. At last, an upregulation of Nrf2 expression under oxidative challenges was found, supporting the activation of endogenous antioxidant defenses. The extract was characterized for phenolic content by spectrophotometric and chromatographic methods. These findings demonstrate that mountain E. purpurea root extract exerts multifactorial cytoprotection via direct antioxidant action and Nrf2 pathway modulation, highlighting its potential as a nutraceutical candidate for maintaining intestinal homeostasis.