Preliminary Study On Alleviating Effect Of Esculin On Oxidative Stress And Its Mechanism

Longevity is the eternal pursuit of people.With the continuous improvement of medical technology,the average life expectancy of human beings has been continuously extended,which has accelerated the process of social aging.Along with this,the incidence of various aging-related diseases is also increasing year by year,such as Alzheimer’s disease(AD)in neurodegenerative diseases,and diabetes in metabolic diseases.A large number of studies have shown that oxidative damage is an important cause directly leading to the occurrence of aging and aging-related diseases.Therefore,searching for drugs with anti-oxidative stress is an important direction in anti-aging research.In recent years,natural antioxidants with low toxicity,high efficiency and abundant resources have become the object of people’s research.And in many studies,it has been confirmed that flavonoids,polysaccharides and other components derived from traditional Chinese medicine have good antioxidant activity.Traditional Chinese medicine has complex chemical components and diverse pharmacological activities.Therefore,it is of great significance to strengthen the research on the activity of single ingredients in Chinese medicine for enhancing the application of Chinese medicine in anti-oxidation and delaying aging.In this paper,the Caenorhabditis elegans(C.elegans)model is used to prove the protective effect of Esculin,a component of Cortex Fraxini,on oxidative stress and its mechanism.we uses DPPH and paraquat(PQ)to explain the antioxidative activity of Esculin in both in vivo and in vitro.On this basis,the food intake rate,body length and spawning of C.elegans were used as indicators that it was in a normal growth state.The results showed that Esculin had good DPPH free radical scavenging ability in vitro and oxidative stress resistance in vivo,and Esculin had no effect on the growth and development of C.elegans.Then the protective effect of Esculin was evaluated by measuring the enzyme activity,ROS level and life span of nematodes.The result demonstrated that Esculin can not only prolong the lifespan of wild-type C.elegans N2 and AD disease model CL2006,but also enhance the antioxidant defense system in nematodes,such as increasing the activity of superoxide dismutase(SOD)and catalase(CAT),and reduce reactive oxygen species(ROS)and the product of lipid peroxidation malonyldialdehyde(MDA)level.Then the visualized transgenic nematodes GR1352,CF1553 and CL2070 were used to study the mechanism of Esculin protection.Further research showed that Esculin can promote the nucleation of DAF-16 transcription factor and the expression of stress-related factors sod-3 and hsp-16.2.Furthermore,the mechanism of protection of Esculin was further studied by mRNA sequencing of nematode model,Quantitative Real-time PCR was used to verify the sequencing results,qPCR results showed that Esculin can increase the expression of sod-3,hsp-16.11 and hsp-16.2 genes,but not DAF-16.In summary,Esculin has good antioxidant activity and significant antioxidant and anti-aging effects to C.elegans.its mechanism may be the activation of antioxidant-related genes downstream of DAF-16.