Partitioning and in vitro bioaccessibility of apple polyphenols during mechanical and physiological extraction: A hierarchical clustering analysis with LC-ESI-QTOF-MS/MS.

Polyphenol partitioning during mechanical (cold-pressing) and physiological (digestion) extraction at the individual polyphenol and subclass level was investigated. UHPLC-ESI-QTOF-MS/MS analysis yielded a comprehensive identification of 45 polyphenols whose semi-quantification revealed a hierarchical clustering strongly determined by polyphenol structure and their location within the apple tissue. For instance, pomace retained most flavonols and flavanols (degree of polymerization DP 5-7), which were highly hydrophobic, hydroxylated, or large (>434 Da), and more abundant in peel. In vitro digestion UHPLC-ESI-QTOF-MS/MS analysis of whole apple (and its corresponding matrix-free extract) clustered polyphenols into five main groups according to their interaction with plant cell walls (PCWs) during each digestion phase. This grouping was not reproduced in pomace, which exhibited a greater matrix effect than whole apple during oral and gastric digestion. Nevertheless, the interaction between most polyphenol groups, including dihydrochalcones, flavanols (DP 1-4) and hydroxycinnamic acid derivatives, and pomace PCWs was lost during intestinal digestion.

Caveolin Delivered by Ultrasound-Mediated Microbubble Destruction Prevents Endothelial Cell Proliferation.

Introduction: The nitric oxide synthase (eNOS) is an important regulator of vascular homeostasis. eNOS is modulated by intracellular mechanisms that include protein-protein interaction with Caveolin-1 (Cav). Cav binds to and impairs eNOS activation reducing vascular permeability and angiogenesis. Blocking of eNOS by Cav has been proposed as therapeutic antiangiogenic approach. However, the efficient and controlled delivery of the peptide requires to be solved. Methods: The effect of antennapedia (AP)-Cav loaded into microbubbles (MBs) and delivered by ultrasound-mediated microbubble destruction (UMMD) into brain endothelial cells (bEnd.3 cells) was evaluated on NO production using DAF2-DA, cell migration assessed by the wound healing assay, cell proliferation with BrdU, and ex-vivo angiogenesis in rat aortic rings. Results: An enhanced inhibitory effect of AP-Cav was observed on cells treated with UMMD. MBs and ultrasound disruption delivery of AP-Cav increased acetylcholine-induced NO release, wound healing, cell proliferation, and angiogenesis inhibition on bEnd.3 cells, compared to free AP-Cav administration. Conclusion: We demonstrated that the delivery of Cav via AP-Cav-loaded MBs and UMMD may be an administration method for Cav that would increase its therapeutic potential by enhancing efficacy and cellular specificity.