Effects Of Ferulic Acid Analogues On Prednisone-induced Oxidative Stress In Mice

Oxidative stress will break down the body's antioxidant defense and cause oxidative damage to the body,which is also the pathogenesis of some diseases.The mitochondria are the main sites for the generation of reactive oxygen species.Ferulic acid,curcumin and oryzanol all have the similar molecular structure,and previous research has proven that they all have antioxidant effects.Prednisone is a glucocorticoid.Large-dose injections of prednisone can disrupt the HPA axis hormone secretion in mice,which can cause stress and increase the content of reactive oxygen species.Therefore,in this experiment,prednisone-induced oxidative stress mice were used as experimental objects,and ferulic acid,curcumin,oryzanol,and coenzyme Q10 were added to the diet to compare the differences in the antioxidant effects of these substances in vivo,and compare their improvement on mitochondrial oxidative stress to determine whether their antioxidant effect in the body is related to their fat solubility,and provide a reference for their application in antioxidants.The experimental design was as follows,90 male ICR mice were randomly divided into 6groups:normal group,model group,ferulic acid group,curcumin group,oryzanol group and positive control(coenzyme Q10)group.Every 3 days,normal group was injected with normal saline intramuscularly,and other groups were injected with 40 mg/kg body weight of prednisone for modeling.The normal group and the model group were fed with normal feed,and the other four groups were fed with 40 mg/kg of ferulic acid,curcumin,oryzanol,and coenzyme Q10.Weight was measured regularly,and behavioral experiments,sugar preference and forced swimming,were started after 4 weeks of feeding.Samples were taken for analysis after 8 weeks of feeding.Determination of oxidative stress-related indicators and Nrf2/ARE signaling pathway-related gene expression in plasma,liver,heart,and muscle tissues;determination of stress-related hormone levels in hypothalamus,pituitary,and plasma;determination of plasma and jejunum inflammation indicators;determination of antioxidant enzyme activity and energy metabolism-related indicators and signaling pathway gene expression levels in mitochondria.The study found that oxidative stress can make mice to lose weight,increase depression,reduce the activity of antioxidant enzymes in the body,and cause inflammation,destroying mitochondrial structure and function.Ferulic acid,curcumin,oryzanol,and coenzyme Q10 all have certain improvements.Among them,oryzanol and coenzyme Q10 significantly improved the weight loss caused by oxidative stress;three ferulic acid analogs and coenzyme Q10significantly reduced the secretion of HPA axis hormones in mice and improved the stress level of mice;oryzanol and coenzyme Q10 significantly increased the levels of 5-hydroxytryptamine(5-HT)and norepinephrine(NE)hormones to reduce depression level.Curcumin,oryzanol and coenzyme Q10 significantly reduced the time for mice to swim in the state of despair,and coenzyme Q10 significantly increased the degree of sugar preference;oryzanol and coenzyme Q10 significantly reduced the content of ROS and malondialdehyde(MDA)in the plasma and tissues of mice,and significantly increased the activities of catalase(CAT),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)antioxidant enzymes,ferulic acid analogs and coenzyme Q10 can also increase the total antioxidant capacity of the body through the Nrf2/ARE signaling pathway.Curcumin,oryzanol and coenzyme Q10 significantly reduced the content of proinflammatory factors,IFN-?,TNF-?and IL-6,and significantly increased the content of the inhibitory factor IL-10;oryzanol and coenzyme Q10 were significantly increased IgG and IgM levels in plasma and jejunum of mice.Ferulic acid analogues and coenzyme Q10 also improved the damage of mitochondrial structure and function caused by oxidative stress.Oryzanol and coenzyme Q10 significantly increased the activity of Mn-SOD and GSH-Px antioxidant enzymes in mitochondria;ferulic acid analogues and coenzyme Q10 also increased the levels of NADH/NAD~+,acetyl CoA and cytochrome P450,and increased the expression levels of energy metabolism related genes,PGC-1?and TFAM,to maintain normal mitochondrial function.The comprehensive results of all experiments showed that under the conditions of this experiment,the antioxidant effect of ferulic acid analogs and coenzyme Q10 is different:ferulic acid<curcumin<oryzanol<coenzyme Q10.Combined with their liposolubility,it can be preliminarily judged that the difference in their antioxidant effects may be related to their degree of liposolubility.