Cichoric acid regulates the hepatic glucose homeostasis via AMPK pathway and activates the antioxidant response in high glucose-induced hepatocyte injury

Abstract

Cichoric acid (CA), a plant-based nutraceutical, is extracted from Echinacea purpurea and other edible plants and vegetables and exhibits multiple biological functions, including antioxidant and hypoglycemic effects. The objective of this study was to determine the effect of CA on the energy regulation pathways and the antioxidant response system in insulin resistance and diabetes-induced hepatic injury and the underlying molecular mechanisms. The streptozotocin-induced diabetic C57BL/6J mice and glucosamine-induced HepG2 cells were observed to evaluate the hepatic protective effects of CA. Compared to the control, CA (60 mg kg⁻¹ d⁻¹, in drinking water for 4 weeks) inhibited hepatic injury and chronic inflammation in diabetic mice via antioxidant defence and regulated the balance of gluconeogenesis and glycolysis. CA (100 μM) regulated glucose metabolism and activated antioxidant response in glucosamine-induced HepG2 cells. CA increased the phosphorylation of the AMP-activated protein kinase and glycogen synthase kinase-3β and stimulated glycogen synthesis and glucose uptake. CA also activated the Nrf2-Keap1 pathway and increased the antioxidant enzyme expression. CA is a potential natural nutraceutical for regulating hepatic glucose homeostasis and antioxidant response, which improved insulin resistance and hepatic injury in diabetes.