pelargonidin-3-glucoside and protocatechuic-acid

Formation of advanced glycation end products (AGEs), which are associated with diabetes mellitus, contributes to prominent features of osteoarthritis, i.e., inflammation-mediated destruction of articular cartilage. Among the phytochemicals which play a role in anti-inflammatory effects, anthocyanins have also been demonstrated to have anti-diabetic properties. Purple corn is a source of three major anthocyanins: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside. Purple corn anthocyanins have been demonstrated to be involved in the reduction of diabetes-associated inflammation, suggesting that they may have a beneficial effect on diabetes-mediated inflammation of cartilage. This investigation of the chondroprotective effects of purple corn extract on cartilage degradation found a reduction in glycosaminoglycans released from AGEs induced cartilage explants, corresponding with diminishing of uronic acid loss of the cartilage matrix. Investigation of the molecular mechanisms in human articular chondrocytes showed the anti-inflammatory effect of purple corn anthocyanins and the metabolite, protocatechuic acid (PCA) on AGEs induced human articular chondrocytes via inactivation of the NFκb and MAPK signaling pathways. This finding suggests that purple corn anthocyanins and PCA may help ameliorate AGEs mediated inflammation and diabetes-mediated cartilage degradation.

Topics: Anthocyanins; Cartilage; Cell Line; Chondrocytes; Diabetes Complications; Diabetes Mellitus; Glucosides; Glycation End Products, Advanced; Glycosaminoglycans; Humans; Hydroxybenzoates; Inflammation; MAP Kinase Signaling System; NF-kappa B; Osteoarthritis; Zea mays

This study hypothesized that the predominant strawberry anthocyanin, pelargonidin-3-O-glucoside (Pg-3-glc), and 3 of its plasma metabolites (4-hydroxybenzoic acid, protocatechuic acid, and phloroglucinaldehyde [PGA]) would affect phagocytosis, oxidative burst, and the production of selected pro- and anti-inflammatory cytokines in a whole blood culture model. For the assessment of phagocytosis and oxidative burst activity of monocytes and neutrophils, whole blood was preincubated in the presence or absence of the test compounds at concentrations up to 5 μmol/L, followed by analysis of phagocytic and oxidative burst activity using commercially available test kits. For the cytokine analysis, diluted whole blood was stimulated with lipopolysaccharide in the presence or absence of the test compounds at concentrations up to 5 μmol/L. Concentrations of selected cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-8, and IL-10) were determined using a cytometric bead array kit. There were no effects of any of the test compounds on phagocytosis of opsonized or nonopsonized Escherichia coli or on oxidative burst activity. Pg-3-glc and PGA at 0.08 μmol/L increased the concentration of IL-10 (P<.01 and P<.001, respectively), but there was no effect on tumor necrosis factor-α, IL-1β, IL-6, and IL-8, and there were no effects of the other compounds. In conclusion, this study demonstrated a lack of effect of these compounds on the opsonization, engulfment, and subsequent destruction of bacteria. Pg-3-glc and PGA, at physiologically relevant concentrations, had anti-inflammatory properties; however, effects were modest, only observed at the lowest dose tested and limited to IL-10.

Topics: Adult; Aged; Anthocyanins; Anti-Inflammatory Agents, Non-Steroidal; Benzaldehydes; Cells, Cultured; Cytokines; Dietary Supplements; Escherichia coli; Female; Humans; Hydroxybenzoates; Lipopolysaccharides; Male; Middle Aged; Monocytes; Neutrophils; Osmolar Concentration; Phagocytosis; Pilot Projects; Reproducibility of Results; Respiratory Burst

Current research indicates that anthocyanins are primarily degraded to form phenolic acid products. However, no studies have yet demonstrated the metabolic conjugation of these anthocyanin-derived phenolic acids in humans.. Within the present study, a simulated gastrointestinal digestion model was used to evaluate the potential degradation of anthocyanins post-consumption. Subsequently, cyanidin (Cy) and pelargonidin and their degradation products, protocatechuic acid and 4-hydroxybenzoic acid, were incubated in the presence of human liver microsomes to assess their potential to form hepatic glucuronide conjugates. For structural conformation, phenolic glucuronides were chemically synthesised and compared to the microsomal metabolites. During the simulated gastric digestion, anthocyanin glycosides (200 μM) remained stable however their aglycone derivatives were significantly degraded (20% loss), while during subsequent pancreatic/intestinal digestion only pelargonidin-3-glucoside remained stable while cyanidin-3-glucoside (30% loss) and Cy and pelagonidin aglycones were significantly degraded (100% loss, respectively). Following microsomal metabolism, pelargonidin formed 4-hydroxybenzoic acid, which was further metabolised (65%) to form two additional glucuronide conjugates, while Cy formed protocatechuic acid, which was further metabolised (43%) to form three glucuronide conjugates.. We propose that following ingestion, anthocyanins may be found in the systemic circulation as free or conjugated phenolic acids, which should be a focus of future dietary interventions.

Topics: Analysis of Variance; Anthocyanins; Chromatography, High Pressure Liquid; Digestion; Glucosides; Glucuronides; Humans; Hydroxybenzoates; Intestinal Mucosa; Male; Microsomes, Liver; Parabens