Research On Anti-aging Activity And Mechanism Of Rhodiola Extract

Rhodiola(Rhodiola L.),belongs to perennial herbaceous plant in the Crassulaceae family,is one kind of the natural precious tonics.Rhodiola is rich in polyphenols,which plays an important role in preventing various diseases,such as depression,Alzheimer's disease,Parkinson's disease,hepatitis,cancer,diabetes and cardiovascular and cerebrovascular diseases.However,previous studies mainly focused on the anti-oxidant,anti-fatigue,and anti-altitude sickness activities of Rhodiola,and the anti-aging activity of Rhodiola extract was rarely reported.Therefore,the current study aimed to investigate the composition and content of polyphenols in Rhodiola extract,chemical and cellular antioxidant activity,anti-cancer activity and inducing-apoptosis mechanism on HepG2.Furthermore,the Caenorhabditis elegans(C.elegans)model was selected to study the anti-aging activity and mechanism of the Rhodiola free extract.The main findings are as follows:(1)The composition of the phytochemicals in the free Rhodiola extract(RE)was identified by HPLC,and 6 phenolic substances including 3 phenolic acids(gallic acid,chlorogenic acid and caffeic acid)and 3 flavonoids(epigallocatechin,epigallocatechin gallate,and catechin)were detected,which epigallocatechin gallate(EGCG)content was the highest.The chemical antioxidant(PSC,ORAC)and cellular antioxidant(CAA)methods were utilized to comprehensively evaluate the antioxidant activity of Rhodiola extract,which found that the antioxidant activity of Rhodiola extract(RE)was much higher than that of common fruits.(2)The anti-cancer activity of the free RE was investigated using human liver cancer cells(HepG2)model.The results showed that the apoptosis rate of HepG2 cells in the sample group showed a dose-dependent effect,which mainly through the intrinsic mitochondrial pathway to promote apoptosis.(3)In the anti-aging activity assay of C.elegans,the effect of the free RE on the lifespan and conventional physiological indicators of the worms(lipofuscin,mobility,fecundity,body length)were firstly investigated,and then the anti-stress(heat stress,ultraviolet stress and paraquat oxidative stress)capacity and antioxidant enzymes of nematodes were also explored.It was found that free RE improved the physiological indicators of nematodes without obvious effect on body length.Theresults from antioxidant stress assays showed that RE significantly attenuated the generation of intracellular ROS and MDA and up-regulated the activities of antioxidant enzymes(SOD and CAT),which suggested a possible contribution of antioxidant activity of Rhodiola extract towards its anti-aging effects.(4)The present study mainly investigated the effects of free RE on the expression of antiaging-related genes in nematodes at the molecular level,and nematode mutant strains and nuclear localization assays were used to further verify the effects of key genes.In terms of the underlying molecular mechanism,Rhodiola extract upregulated the gene expression of sod-3,gst-4,daf-16,skn-1 in C.elegans,downregulated the gene expression of daf-2 and age-1,and accelerated the translocation of DAF-16 and SKN-1 into the nucleus.Furthermore,the extension of the lifespan of daf-16(mu86)and skn-1(zu169)mutants was abolished by RE.These results demonstrated that RE could enhance lifespan extension,healthspan and stress resistance of C.elegans via insulin/IGF signaling and SKN-1 pathway.