| Rationales:Aging is an irresistible physiological change caused by the aging of tissues and cells and the decline of organ functions with the growth of age.Chronic diseases caused by aging already account for 33% of the disease burden in China.Healthy aging of the elderly has become one of the hot spots and difficult problems in modern medicine.Codonopsis Pilosula(C.Pilosula),as a medicinal and edible material,has a wide range of pharmacological activities,such as antioxidant,enhancement of immunity and anti-inflammatory and so on.However,its anti-aging activity and its mechanism are still unclear.The Yellow Emperor’s Canon of Medicine Plain Conversation in the Tang Dynasty : " What you eat on an empty stomach is food,and what the patients eat is medicine.".It reveals the idea of homology of medicine and food,that is,to control or even treat diseases by means of diet therapy in order to prolong life.The clinical medication method of traditional Chinese medicine is decoction,so this paper studies the anti-aging effect of water extract of C.pilosula(WECP)on Drosophila melanogaster(D.melanogaster)and its related mechanism.Objective:To confirm the anti-aging effect of WECP on D.melanogaster,and explain the mechanism from multidimensional perspective.Methods:1.Study on anti-aging effect of WECP.In order to screen out the best administration time and dose,the different concentrations(0,3,9,15 mg/m L)of WECP were applied in the lifespan assays during the young stage(15-35 days)and the old stage(30-45 days).The effects of WECP on food intake,climbing ability and sexual activity of D.melanogaster were investigated under the optimum administration time and concentration.2.Study on the mechanism of WECP delaying senescence of D.melanogaster.The mechanism of WECP delaying aging was preliminarily predicted by network pharmacology,and the prediction pathway was verified by RT-q PCR.The UHPLC-Q-TOF-MS/MS metabolomics technology was used to explore the effects of WECP on metabolism.The effect of WECP on intestinal bacteria of D.melanogaster was analyzed by 16 S rRNA gene sequencing.Finally,the correlation between differential metabolites and intestinal bacteria was analyzed to explore the anti-aging mechanism of C.pilosula.The antioxidant effect of WECP on D.melanogaster was investigated by paraquat and hydrogen peroxide injury model.The activities of antioxidant enzymes SOD and CAT and the expression of related genes in vivo were determined.Results:1.The optimal dose was 9 mg/m L WECP at the young stage(15-35days).At the optimal time of administration,the climbing ability and sexual vitality of D.melanogaster were improved,but the food intake was not affected.3,9 and 15mg/m L WECP at the old stage(30-45 days)could prolong the life span of both males and females.But the overall effect was inferior to that of positive control group VE.2.Network pharmacology studies showed that the WECP may delay aging through PI3K-Akt pathway.3.Metabonomics analysis was performed on the 3 d,20 d and 20 d+9 mg/m L WECP groups.Eight different metabolites were found : Palmitoylethanolamide,L-Phenylalanine,L-Glutamine,Glycerol,1-hexadecanoate,Erucamide,Dl-Dihydrosphingosine,3-(1-Pyrazolyl)-L-alanine,Dodecylamine.These differential metabolites are involved in amino acid metabolism pathways(phenylalanine,tyrosine,and tryptophan biosynthesis pathways : L-phenylalanine;Phenylalanine synthesis pathway : L-phenylalanine;Metabolism of alanine,aspartate,and glutamate :L-glutamine).After administration of 9 mg/m L WECP,the proportion of Lactobacillus in the intestinal flora of D.melanogaster decreased,the Acetobacter is increased,indicating that the WECP can improve the proportion of probiotics in D.melanogaster to a certain extent,allow the fruit fly body to develop in a healthy state.The correlation analysis results showed that there was a significant relationship between phenylalanine and intestinal flora.The results of antioxidant research showed that the WECP could delay aging through antioxidant,but it has nothing to do with the activities of SOD and CAT.Conclusion:The WECP can prolong the life span of D.melanogaster.It has no effect on the food intake of fruit flies,and can improve the exercise ability and sexual vitality of fruit flies.The WECP may play an anti-aging effect by regulating the PI3K-Akt signaling pathway,improving the proportion of probiotics to a certain extent in D.melanogaster,and regulating the D.melanogaster phenylalanine metabolic pathway. |
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