chicoric-acid and Hyperglycemia

Endothelial dysfunction is a driving force during the development and progression of cardiovascular complications in diabetes. Targeting endothelial injury may be an attractive avenue for the management of diabetic vascular disorders. Chicoric acid is reported to confer antioxidant and anti-inflammatory properties in various diseases including diabetes. However, the role and mechanism of chicoric acid in hyperglycemia-induced endothelial damage are not well understood.. In the present study, human umbilical vein endothelial cells (HUVECs) were incubated with high glucose/high fat (HG + HF) to induce endothelial cell injury.. We found that exposure of HUVECs to HG + HF medium promoted the release of cytochrome c (cytc) from mitochondrion into the cytoplasm, stimulated the cleavage of caspase-3 and poly ADP-ribose-polymerase (PARP), then inducing cell apoptosis, the effects that were prevented by administration of chicoric acid. Besides, we found that chicoric acid diminished HG + HF-induced phosphorylation and degradation of IκBα, and subsequent p65 NFκB nuclear translocation, thereby contributing to its anti-inflammatory effects in HUVECs. We also confirmed that chicoric acid mitigated oxidative/nitrative stresses under HG + HF conditions. Studies aimed at exploring the underlying mechanisms found that chicoric acid activated the AMP-activated protein kinase (AMPK) signaling pathway to attenuate HG + HF-triggered injury in HUVECs as AMPK inhibitor Compound C or silencing of AMPKα1 abolished the beneficial effects of chicoric acid in HUVECs.. Collectively, chicoric acid is likely protected against diabetes-induced endothelial dysfunction by activation of the AMPK signaling pathway. Chicoric acid could be a novel candidate for the treatment of the diabetes-associated vascular endothelial injury.

Topics: AMP-Activated Protein Kinases; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Caffeic Acids; Cell Survival; Cytochromes c; Cytoplasm; Endothelium, Vascular; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Inflammation; L-Lactate Dehydrogenase; Mitochondria; Nitrosative Stress; Oxidative Stress; Poly(ADP-ribose) Polymerases; RNA, Small Interfering; Succinates

Cichoric acid (CA), extracted from edible plants and vegetables, is a potential natural nutraceutical, with antioxidant and hypoglycaemic biological functions. The objective of this study was to explore the potential underlying molecular mechanisms involved in normalizing diabetes-related changes in hyperglycaemia via pancreas apoptosis and muscle injury induced by multiple low-dose STZ (MLD-STZ) injection in response to dietary supplementation with CA. To induce the MLD-STZ diabetic mice, the C57BL/6J mice were intraperitoneally injected with STZ (50 mg/kg body weight) for consecutive five days. CA (60 mg/kg/d) was supplemented in drinking water for 4 weeks. Compared with control, CA inhibited pancreas apoptosis and adjusted islet function in diabetic mice, leading to an increase in insulin generation and secretion. Moreover, CA regulated mitochondrial biogenesis, glycogen synthesis, and inhibited inflammation via activating antioxidant responses, which contributes to the improvement in athletic ability and diabetic myopathy. In general, CA is a natural food-derived compound with the potential application for regulating glucose homeostasis and improving diabetes and its complications.

Topics: Animals; Blood Glucose; Caffeic Acids; Diabetes Mellitus, Experimental; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Mice; Mice, Inbred C57BL; Muscles; Pancreas; Streptozocin; Succinates