Effects And Mechanism Of Sesamol On Systemic Oxidative Stress And Nrf2/ARE Antioxidant Defense Signaling Pathways

Population aging has become an increasingly serious social problem.The health problem of it increases the public responsicity gradually.Oxidative stress is a process that the body generates and accumulates a large number of free radicals when it removes the damaged cells or subjected to harmful stimuli.This process might cause the redox imbalance and lead to tissue oxidation of biological molecules.Sesamol is one of the fat-soluble lignans compounds in sesame or sesame oil.It has antibacterial and antioxidant activity and it's also used as an excellent non-toxic antioxidants.Previous studys show the antioxidant activity of sesamol,which could protect the neuronal from oxidative damage.However,there is no research about the mechanism of sesamol on regulating the Nrf2/ARE antioxidant defense signal pathway.The present study investigate the molecular mechanism of NRf2/ARE antioxidant defense signal pathway regulated by sesamol on cells and mice.Oxidative stress of C57BL/6J mice were induced by injecting D-galactose.After 3 days,mice were sacrificed and observed the following indexes:?1?Plasma SOD,CAT and MDA?2?Histopathological observation in brain and liver.The effect of sesamol regulating oxidative stress mice induced by D-galactose in learning and memory ability and the protective function of sesamol on regulating Nrf2/ARE antioxidative defense signal pathway were also observed.The results showed that:?1?sesamol significantly decreased the plasma SOD and CAT levels while increased the MDA level induced by oxidative stress;?2?sesamol significantly increasedf?3?in open field test,Y-maze,morris water maze,we found that cells damage in the hippocampal and liver;?3?Galactose-induced oxidative stress in mice,the ability of learning and memory in mice decreased,and after the intervention of sesamol tends to recover.?4?The analysis of protein expression of Nrf2/ARE signaling pathway,sesamol could up-regulate the expression of two-phase enzymes HO-1 and NQO1.In cells experiments,?1?H₂O₂induced the oxidative stress of SH-SY5Y,BRL-3A.It increas ROS,and the treatment of sesamol could significantly inhibit this phenomenon;?2?H₂O₂ induced the oxidative stress of SH-SY5Y and BRL-3A cells.It can decrease the mitochondrial membrane potential and reduced the red fluorescence of JC-1.The addition of sesamol significantly increased the mitochondrial membrane potential:?3?The results showed that the expression of Nrf2 and Keap1 was down-regulated by H₂O₂ induction,meanwhile the expressions of HO-1 and NQO1 were also decreased.The Nrf2/ARE signal pathway was activated and the expression of HO-1 and NQO1 was enhanced after the treatment of sesamol which promoted the oxidative stress of Nrf2 cells.