Cytoprotective effects of iridoids from Gaultheria spp. berries in gastric and intestinal epithelial cells after in vitro digestion

Reactive oxygen species may induce oxidation of macromolecules in foods and during digestion in the gastrointestinal tract, negatively impacting human health. Antioxidants present in plant foods, including carotenoids, tocochromanols, ascorbic acid, as well as (poly)phenols and iridoids, may counteract oxidation of macromolecules. The aims of the present study were to determine the contents of carotenoids, tocochromanols, ascorbic acid from Gaultheria spp. berries and to investigate the cytoprotective and antioxidant activities of the fruit extracts and monotropein esters present in the berries. Moreover, the underlying mechanisms of action in gastrointestinal epithelial cells after in vitro digestion was also investigated. The content of ascorbic acid ranged from 3 to 24 mg/ 100 g fw, carotenoids from 9 to 56 mu g/100 g fw, and total tocochromanols from 0.29 to 0.45 mg/100 g fw. The pre -incubation of gastric (AGS) and intestinal (Caco-2) cells with Gaultheria fruit extracts significantly increased viability of cells stressed with 10 mM H2O2 and 100 mM AAPH, respectively, compared to control cells. Furthermore, digested Gaultheria fruit extracts and monotropein esters increased the relative mRNA of the Nrf2/ Keap1/ARE antioxidant signaling pathway and enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and reductase, and catalase (CAT). The pre -incubation of Caco-2 cells with digested monotropein and monotropein esters increased the protein expression of GPX, CAT, Keap1, and Nrf2, and incremented the SOD activity in Caco-2 cells. In conclusion, Gaultheria spp. fruit extracts and monotropein esters may protect gastrointestinal epithelial cells against oxidative stress during digestive processes.