Study On The Anti-aging Effect Of Naringenin On Caenorhabditis Elegans

Naringenin（NN）is one of the most abundant flavonoids in citrus and grapefruit,which can effectively scour free radicals and is a fairly effective antioxidant.In this study,the antioxidant and anti-aging activities of NN in Caenorhabditis elegans（C.elegans）were investigated,and the molecular mechanism of its anti-aging effect was further discussed.In this study,C.elegans was selected as an aging animal model to explore the anti-aging potential of NN and its molecular mechanism.After treated with or without different concentrations of NN（50、100 and 200μmol/L）,lifespan,stress resistance,pharyngeal pumping and locomotion capability were examined.Meanwhile,the accumulation of age pigment and reactive oxygen species（ROS）were determined.Besides,the indicators of age-related neurodegenerative disorder including paralysis,chemotaxis behavior,poly Q accumulation,the death of ASH neuron and avoidance behavior were tested.The activity of antioxidant enzymes and m RNA expression levels of related genes were determined to further explore the molecular mechanism of NN to delay aging.The results showed that NN could significantly prolong the lifespan of C.elegans under normal culture condition,and improve the ability of C.elegans to resist oxidative stress under H₂O₂-induced acute oxidative stress.After the treatment of NN,the locomotion capability of C.elegans was improved and pigment accumulation was inhibited.In addition,NN delayed body paralysis induced by Aβprotein in AD transgenic CL4176 worms,and reversed chemotaxis behavior defects induced by Aβprotein aggregation in CL2355 worms.NN inhibited poly Q aggregation in HD transgenic AM141 worms,reduced ASH neuron death induced by poly Q aggregation,and had protective effect on behavioral dysfunction induced by neuron defects in HD transgenic HA759 worms.NN treatment significantly increased the activity of antioxidant enzymes,decreased the accumulation of ROS and the content of malondialdehyde（MDA）in C.elegans.RT-PCR analysis showed that NN up-regulated the expression levels of daf-16,sek-1 and skn-1,down-regulated the expression levels of daf-2,age-1 and akt-1,and further activated the downstream sod-3,ctl-1,ctl-2,gst-4 and mtl-1.In addition,molecular docking was used to conduct computer simulation,and the evaluation results showed that NN could interact with key proteins in IIS and MAPK pathways by hydrogen bonding.These results further indicated that IIS and MAPK pathways may be involved in the regulation of NN-mediated anti-aging effect in C.elegans.In conclusion,NN can significantly prolong the lifespan of C.elegans,enhance oxidative stress resistance,and improve various physiological indicators of C.elegans.NN can regulate the antioxidant and anti-aging ability through IIS and MAPK pathways in C.elegans.