Plasma proteome profiling reveals molecular mechanisms underlying the effects of daily consumption of ‘Bahia’ and ‘Cara Cara’ orange juices

Abstract

Orange juice is an important food source of bioactive compounds, mainly the flavanones hesperidin and narirutin. This study aimed to investigate the underlying molecular mechanisms of action of orange juice's health properties by analyzing changes in the plasma proteome of healthy Brazilian volunteers after consuming juices made from ‘Bahia’ (BOJ—source of flavanones) and ‘Cara Cara’ (CCOJ—source of flavanones and carotenoids) oranges cultivated in Brazil. We used an untargeted proteomic approach, with a particular emphasis on the juices’ effects on blood coagulant activity. We identified 247 differentially expressed proteins, of which 170 significantly increased or decreased after BOJ consumption and 145 after CCOJ. These proteins are involved in 105 processes that can significantly regulate cell adhesion, cell signaling, cell metabolism, inflammation, or others. Bioinformatic analysis evidenced proteins with major cellular regulatory capacity (e.g., FN1 and GAPDH) and predicted transcription factors (TFs) (e.g., SP1 and CEBPA) and miRNAs (e.g., miR-1-3p and miR-615-3p) that could be involved in the regulation of differentially expressed proteins. In-silico docking analyses between flavanone metabolites and TFs evidenced the higher binding capacity of narirutin phase II metabolites with akt1 and p38, interactions that suggest how the expression of genes of differentially expressed proteins were activated or inhibited. Moreover, the study shed light on proteins of coagulation cascade that presented expression modulated by both juices, proposing the modulation of blood coagulant activity as a potential benefit of OJ (mainly CCOJ) consumption. Taken together, this study revealed that BOJ and CCOJ consumption affected plasma proteome in healthy individuals, suggesting potential molecular targets and mechanisms of OJ bioactive compounds in humans.