The second life of Citrus bergamia: bioavailability analysis of a new formulation using waste-based microencapsulation as a valuable source of bioactive compounds

Background: Polyphenols have garnered significant interest because of their potential health benefits, but their bioavailability is limited. According to recent studies, in vivo metabolites of phenol compounds may mediate their biological activity, potentially countering systemic oxidation and inflammation and therefore reducing multi-organ dysfunction associated with gut microbiota alterations. This pre-clinical study aims to characterize a novel formulation, enhancing metabolite bioavailability, ensuring long-term stability, and employing sustainable production methods. Our research provides the first evidence of the presence of these metabolites in the blood plasma of animals receiving different Bergamot polyphenols fraction (BPF) formulations. Methods: Male Sprague-Dawley were used throughout the study. The animals were subdivided into three groups of six animals each receiving 50 mg/kg of BPF standard (BPF), 50 mg/kg of Bergamot polyphenols fraction micronized (BPFmicro), and 50 mg/kgof Bergamot polyphenols fraction encapsulation (BPFencap), respectively, by oral gavage. Blood samples were collected, and plasma was prepared with a specific protocol and analysed for the presence of primary and secondary metabolites through ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results: UHPLC-MS/MS analysis showed significantly higher plasma concentrations of naringin and its metabolites in the BPFencap group compared to the BPF standard and BPFmicro groups at all time points. In comparison to BPF, plasma Area Under Curve (AUC) analysis of metabolites revealed substantially elevated values for the BPFencap group and substantially reduced values for the BPFmicro group. Conclusion: While BPFmicro greatly increased bioavailability, the improvement was only temporary, highlighting a stability problem. The bioavailability and stability of metabolites are significantly improved over time by the new BPFencap formulation (micronized BPF in hybrid phospholipid systems with citrus albedo fibers).