From in vitro antimicrobial activity to enhanced innate immunity in vivo: cornelian cherry (Cornus mas L.) fruit...

The increasing prevalence of antimicrobial resistance and diabetes-associated immune dysfunction necessitates the development of novel natural agents with antimicrobial and immunomodulatory properties. Cornelian cherry fruits are rich in bioactive phytochemicals (anthocyanins, iridoids, phenolic acids, and flavonols).This study evaluated the antimicrobial activity of fruit extracts from C. mas cultivars `Podolski´ , `Yantarnyi´ & `Flava´ , as well as loganic acid extract - the main iridoid glycoside of `Yantarnyi´ and `Flava´ fruits. Antimicrobial effects were assessed in vitro against Gram-positive bacteria (Bacillus cereus, Staphylococcus epidermidis), Gram-negative bacteria (Proteus vulgaris, Escherichia coli), the phytopathogenic bacterium (Clavibacter michiganensis), and yeasts (Saccharomyces cerevisiae, Yarrowia lipolytica). In vivo, the effects of the extracts on innate immune responses were investigated in streptozotocin-induced diabetic rats treated orally with extracts (20 mg/kg b.w./day for 14 days) by analysing phagocytic activity and oxygen-dependent microbicidal responses of peripheral blood leukocytes. The extracts inhibited microbial growth in a concentration-dependent manner, with the `Podolski´ extract already at the contentration 2.5 mg/mL exhibiting the strongest antimicrobial activity, whereas the loganic acid extract showed the weakest effect. In diabetic rats, the extracts enhanced leukocyte antimicrobial functions, including phagocytic activity and intracellular killing capacity. Extract from the `Podolski´ cultivar exerted the most pronounced effects: it increased the phagocytic index by 33% and phagocytic number by 2.8-times, elevated the activity of superoxide dismutase and myeloperoxidase by 1.9- and 2.9-times, respectively, and decreased intracellular ROS levels (41%). These changes were accompanied with enhanced glucose uptake (24%) and ATP levels (10%) in leukocytes, consistent with the metabolic demands of phagocytosis and indicating correction of diabetes-associated immunometabolic disturbances. Overall, the findings indicate that cornelian cherry fruit extracts may serve as promising natural antimicrobial agents and enhancers of innate immune effector functions, with potential applications in diabetic immune dysfunction and infectious complications.