Regulatory Mechanism Of Antioxidant Defence Enzymes By Chicoric Acid

Chicoric acid,a nutritional component found in a typical Mediterranean vegetable chicory,possesses multiple biological properties including antioxidant activities,anti-obesity effects,anti-HIV,and others.However,there have been very few studies of its effects to counter oxidative stress-induced cognitive loss.To address this,the goal of this study was to investigate the effects of chicoric acid on biomacromolecule against oxidative damage,and to investigate its antioxidant activities and the underlying mechanisms in cellular and animal models.The main investigations and results are as follows:?1?8 week-old C57BL/6J mice were divided into 3 groups and treated with or without chicoric acid?CA;100 mg/kg body weight?administered in the drinking water and standard diet.At the same time,the mice were treated by daily intraperitoneal injection of D-galactose?D-gal;300 mg/kg/day?for two months.?2?The learning and memory ability was assessed using the Y-maze and Morris maze test.In this study,chronic injection of D-gal impaired working memory and reference memory in the Y-maze and Morris water maze tests,respectively,without changing locomotive activity,with prolonged crossing times,escape latency,and shortened target quadrant occupancy in mouse behavioral studies.However,CA reversed the D-gal-elicited deterioration of spatial learning abilities at a daily dose of 100 mg/kg body weight for 8 weeks.?3?CA was attenuated neuron damage in D-gal-treated mice as revealed through histological examination in the hippocampus regions of the mouse brains.Our study found that CA treatment inhibited the increased expression of A?proteins in the hippocampus of the D-gal-treated mice by minimizing oxidative stress,suggesting that CA treatment effectively ameliorates oxidative damage and improved indexes related to aging and AD in D-gal-treated mice.Then,the levels of inflammatory mediators,such as TNF-?and IL-1?,as well as malondialdehyde levels were markedly reduced after CA treatment.In contrast,the activity of CAT and the level of GSH were significantly elevated in serum by CA.?4?Moreover,the efficacy of up-regulated the expression of antioxidants defence enzymes with CA was investigated.We found that CA could improve phase II antioxidant enzymes including HO-1 and NQO1 expressions in D-gal-induced mice brain and liver both in protein levels and mRNA levels.The results also revealed that CA treatment noticeably activated the Nrf2 antioxidative defense system by up-regulation of downstream antioxidant enzyme expression in the animal.?5?To make the results more convicing,H₂O₂ was used to stimulate the situation of D-gal-lesioned oxidative damage.The results demonstrated that CA significantly reversed H₂O₂-elicited SH-SY5Y cells and HepG2 cells viability decrease,mitochondrial dysfunction,eventually disrupt cellular function in the cell models.More significantly,in this study also suggested that CA supplementation strongly enhanced the expressions of antioxidant enzymes including HO-1 and NQO1,activating Nrf2 pathway via balancing cellular redox status in H₂O₂-induced SH-SY5Y cells and HepG2 cells,respectively,indicating that CA has great potential for use as part of a nutritional preventive strategy to counter oxidative stress-related cognitive impairment and aging.