Bean seed persimmon peel cinnamon twigHuman Human Mice Mice Mice Mice Human Mice Human Mice Mice RatsHsu et al., 2020 Macho-Gonz ez et al., 2020 Anuncia o et al., 2018 Wang et al., 2020 Bang et al.,[210] [211] [212] [213] [214]C. obtusa var. PAK6 custom synthesis formosana leaf carob fruit extract extruded sorghum C. osmophloeum and T. camphoratus EnzogenolRats Rats Human Mice MiceAntioxidants 2021, ten,22 ofFigure 15. Schematic representation from the molecular mechanisms via which PACs affect glucose metabolism guarding NPY Y5 receptor supplier against hyperglycemia. boost; lower. The figure was produced working with Servier Health-related Art by Servier (clever.servier.com, accessed on 12 March 2021), licensed under a Creative Commons Attribution 3.0 Unported License).7.1.1. Gut: Carbohydrate Digestion and Glucose Absorption Complicated carbohydrates, after reached the compact intestine, are mainly digested by -amylase and -glucosidase, two key carbolytic enzymes involved in post-prandial glycemic response, which convert them into monomers. The latter are then incorporated by enterocytes by means of precise transporters localized at the apical side of their brush border membrane. Amongst them, sodium-dependent glucose transporter (SGLT1) and glucose transporter GLUT2are inhibited by PACs [215], thus stopping glucose absorption. Glucose tolerance was also located to be favored by PACs due to their capability to market, each in vitro and ex vivo, the secretion of glucagon-like-peptide-1 (GLP-1), probably the most essential satiety-related enterohormones: grape seed proanthocyanidins extracts (GSPE) stimulate GLP-1 secretion in the ileum, whereas unabsorbed or metabolized forms do the exact same in the colon probably via MAPK and ERK1/2 pathways [216,217]. The suppression of GLP-1 secretion appears to become dependent from PAC concentration and its subsequent effect on cellular membrane prospective: at low concentrations (0.05 mg/l) GSPE induces depolarization in STC-1 cells, whereas at high concentrations (50 mg/l) it leads to hyperpolarization along with the concomitant suppression of GLP-1 secretion [218]. In regard to carbohydrates digestion, PACs are in a position to inhibit some digestive enzymes much more than their anthocyanin relatives, suggesting fantastic possible in suppressing the early glycemic spike and therefore stopping T2DM [215,21921]. As an illustration, proanthocyanidin B2 (PB2 ) reversibly and considerably inhibits -glucosidase activity (IC50 = 0.23 0.01 /mL), with only slight impact on -amylase (IC50 = 0.86 mmol/L) on everted intestinal sleeves [185]. ToAntioxidants 2021, 10,23 ofelaborate–PB2 inhibited -glucosidase in a mixed-type manner to interrupt the enzymesubstrate intermediate. Lastly, molecular docking analysis revealed that PB2 interacts with several amino acid residues of -glucosidase, hence inducing a conformational alter, in the end leading to aggregation [185]. PACs activity on digestive enzymes is strictly dependent on their structure: in specific, the amount of hydroxyl groups, their position on the A, B, and C rings [222] as well as the degree of polymerization are vital [215,223]. Interestingly, Zhong and co-workers demonstrated that the PAC-mediated inhibition of some digestive enzymes inside the smaller intestine and pancreas was much more pronounced in mice fed high-degree PACs with respect to these fed low-degree PACs [215]. This effect is likely as a result of presence of a higher quantity of phenolic hydroxyl groups inside the high-polymer PACs, which may establish a bigger number of hydrogen bonds wit.
