A standardized extract of Opuntia ficus-indica (L.) Mill. and Olea europaea L. protects against indomethacin-induced Caco-2 intestinal epithelial cells injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs), widely used for their antipyretic, analgesic and anti-inflammatory effects, can damage the gastrointestinal mucosa, leading to mitochondrial dysfunction, oxidative stress, apoptosis and inflammation, and altering the permeability of the intestinal barrier with consequent cytotoxic effects. Proton pump inhibitors protect against gastric damage induced by NSAIDs but are ineffective for intestinal damage. Today, research has focused on the study of natural products as protective agents for intestinal damage caused by NSAIDs. In this study, a model of intestinal epithelial cells injury induced by indomethacin (INDO) was used to evaluate the in vitro beneficial effects of a standardized extract (OFI+OE), rich in polysaccharides and polyphenols, obtained from cladodes of Opuntia ficus indica (L.) Mill. and from leaves of Olea europaea L. Fully differentiated Caco-2 cells were pretreated with OFI+OE (350 and 700 μg/mL) for 24 h and subsequently exposed to 1 mM INDO for 24 h. Pretreatment with OFI+OE protected cells from INDO-induced epithelial damage, as demonstrated by transepithelial electrical resistance (TEER) measurement, fluorescein permeability, and tight junctions’ expression. The extract significantly reduced oxidative stress, decreasing reactive oxygen species (ROS) levels and increasing total antioxidant activity (TAA), and blocked apoptotic cell death, by modulating Bcl-2, Bax and Caspase-3. Furthermore, the extract inhibited the NF-κB inflammatory pathway. In conclusion, these data support the use of OFI+OE extract as a natural approach for the prevention and treatment of gastrointestinal mucosal damage induced by NSAID, demonstrating its beneficial effects through modulation of oxidative, apoptotic, and inflammatory pathways.