Anti-aging Activity And Mechanism Of Royal Jelly On Natural Aging Mice

Royal jelly is a rich bioactive food secreted by the feeding bee,which has been widely used as a natural multi-functional health food for a long time,and has been proved in a variety of model organisms with antioxidant,immune regulation,lipid metabolism and other effects to promote body health.However,the anti-aging activity of royal jelly in natural aging mouse models and its mechanism remain unclear.Natural aging models can reflect real physiological conditions,which is helpful to better understand the biological mechanisms of aging or the effects of intervention.In this study,C57BL/6J mice were fed royal jelly for 9 months from the age of 9 months to 18 months as the royal jelly intervention group(RJ).At the same time,18-month old mice were used as the old control group(OC)and 3-month old mice as the young control group(YC).The effects and potential mechanisms of royal jelly intervention were gradually analyzed from the perspectives of aging index evaluation,brain lipid and gut barrier,and gut microbiota.The main results are as follows:Firstly,the effects of royal jelly on the body function of natural aging mice were evaluated.The open field and elevated plus maze experiments showed that after royal jelly intervention,the exploratory ability and anxiety behavior of naturall aging mice in a new environment were effectively improved.Compared with OC group,serum triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(ALT)and alanine aminotransferase(AST)in RJ group were decreased by 31.15%,9.96%,22.58%,30.53% and 20.17%,respectively.The expression of inflammatory factors,apoptosis factors,cell cycle-dependent kinase inhibitors p16,p21 and p53 decreased in liver tissue,and increased the activity of antioxidant-related enzymes and the expression of longevity factor genes.Royal jelly can relieve the abnormal lipid metabolism,liver cell cycle arrest,abnormal apoptosis and oxidative stress caused by aging in mice.Secondly,brain lipomic studies showed that compared with OC group,the ratio of monounsaturated fatty acid to polyunsaturated fatty acid(MUFA: PUFA)in RJ group was increased by 23.46%,and the relative contents of specific acylcarnitine Car(C14:1),Car(C20:3)and ether ester were significantly increased.RT-q PCR showed that royal jelly promoted the expression levels of Nrf2 and its downstream target genes HO-1,superoxide dismutase(SOD),glutathione peroxidase-1(Gpx-1),alleviating oxidative stress damage in the brains of natural aging mice.KEGG analysis showed that royal jelly may regulate brain lipid metabolism by regulating glycerol metabolism,fat digestion and absorption,cholesterol metabolism and other 8significant enrichment pathways in natural aging mice.Finally,the intervention effect of royal jelly on natural aging mice was studied from the aspect of intestinal barrier function and gut microbiota.Compared with OC group,the number of colon epithelial cup cells and mucin secretion in RJ group were increased,the expression levels of tight junction protein-closed small loop protein(ZO-1)and Occludin genes were also increased,and the expression levels of TNF-αand IL-6 were decreased.Furthermore,16 S r RNA gene PCR amplification and sequencing analysis showed that royal jelly increased the ratio of Firmicutes to Bacteroides(F/B)in the core bacteria.It also increased beneficial bacteria abundance with anti-inflammatory and intestinal permeability-reducing effects such as Akkermansia and Lachnospira NK4A136 group,meanwhile reducing proinflammatory bacterial abundance such as Ileibacterium and Erysipelotrichaceae.The levels of short-chain fatty acids(SCFAs)such as acetic acid,propionic acid,butyric acid and valeric acid were increased in the feces of RJ group.Spearman correlation analysis revealed that some dominant bacterial groups were significantly correlated with SCFAs,lipid metabolism and brain lipid metabolite parameters.Royal jelly improved intestinal function of natural aging mice,and the relevant indexes in RJ group were close to those in YC group.In conclusion,this paper systematically studied the intervention effects and potential mechanisms of royal jelly on body function,brain lipid composition,intestinal barrier function and gut microbiota of natural aging mice,which can provide important reference value for developing dietary intervention strategies adapted to improving brain health and microbiome regulation in the elderly population.It also provides important insights for further exploring the information exchange mechanism between gut microbiota,gut and brain axis.