Sweet cherry phenolics revealed to be promising agents in inhibiting P-glycoprotein activity and increasing cellular viability under oxidative stress conditions: in vitro and in silico study

This study aimed to explore the total phenolic and anthocyanin content (TPC and TAC, respectively), and the biological potential of Portuguese sweet cherry cultivars. The TPC and TAC values ranged between 72.9 and 493.6 gallic acid equivalents per 100 g fresh weight (fw), and from 1.0 to 179.1 cyanidin 3-O-rutinoside equivalents per 100 g fw, respectively. Cristalina total extract was the most effective in capturing DPPH reactive species, whereas the colored fraction and the total extract of Saco cultivar were the most efficient in scavenging ferric and peroxide species. Celeste total extract was the most effective in inhibiting alpha-glucosidase enzyme. Phenolic-rich extracts and standard phenolics also revealed ability to interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and to increase cellular viability under conditions of oxidative stress. Computational studies were performed to evaluate the interaction between phenolics and the P-gp activity. This study revealed that cherry extracts and their phenolic compounds present notable biological properties, encouraging the development of cherry-based dietary and medicinal supplements. Practical Application The interest in phenolic-rich sources has increased significantly in recent years, given their capacity to prevent the development of chronic disorders, such as cancer. Recent evidence suggests that phenolic compounds can act as P-glycoprotein (P-gp) inhibitors, an important drug efflux transporter, preventing multidrug resistance, and thus, enhancing the therapeutic efficacy of some drugs in certain target cells. Our results indicate that enriched-fractions from sweet cherries can effectively interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and protect against oxidative damage.