The Study On Anti-fatigue Of Ginsenoside Rh1 Based On Metabonomics

Objective: 1.The study aims to discuss the anti-fatigue mechanism of ginsenoside Rh1 from the three aspects of improving the level of glucocorticoid receptor,anti-oxidative stress and promoting metabolism through the establishment of exercise fatigue model.2.We analysis the change of endogenous metabolites in the exercise-induced fatigue rats intervened by ginsenoside Rh1 using GC-TOF-MS technology combined with the multi-dimensional statistical analysis,and confirmed the different related metabolic markers and metabolic pathways,which can provide the possible experiment basis for the alleviation of the exercise-induced fatigue.Methods: A one-week exhaustion training model was established,and different doses of ginsenoside Rh1 suspension were given by intragastric administration.The different kits were used to measure the indexes of blood lactate(BLA),lactate dehydrogenase(LDH),creatine kinase(CK),blood urea nitrogen(BUN),superoxide dismutase(SOD)and malondialdehyde(MDA)immediately after exhausted running.Based on the above experiments,after screening a high-dose ginsenoside Rh1 group with better anti-fatigue effect,The Elisa method measured the content of testosterone and corticosterone in rat serum and the protein expression of glucocorticoid receptor(GR)were measured by western blot immediately after exhaustion.Find out endogenous metabolic markers which were induced by exercise-induced fatigue and intervened by ginsenoside Rh1 through GC-TOF-MS technology of metabolism.Seek the potential differences in metabolites by the multivariate statistical methods and principal component analysis and orthogonal partial least squares.Identify potential biomarkers by the KEGG database which would be entered to MetPA database for the construction and analysis of the corresponding metabolic pathway.Results: 1.After exhaustion in rats,the concentration of blood LA,LDH,CK,BUN,MDA increases(P〈0.01),and the level of SOD decreases(P〈0.01);supplementation of ginsenoside Rh1 can significantly prolong the exhaustion exercise time of rats(P〈0.01)and reduce the concentration of blood LA,LDH,CK,BUN,MDA(P〈0.01),and improve the activity of SOD(P〈0.01).2.After exhaustion,the serum testosterone level of rats decreased(P〈0.01),the level of serum corticosterone increased(P〈0.01),the ratio of T/C decreased(P〈0.01),and the protein expression of GR decreased significantly(P〈0.01).Supplementation of ginsenoside Rh1 can improve the testosterone level(P〈0.01),and the protein expression of GR increased(P〈0.05).3.The results of metabonomics analysis showed that there were 8 different metabolites in the blood of the TrnM group compared with the control group.There were 6 significantlydecreased metabolites and 2 significantly increased metabolites.There are five major metabolic disorder systems caused by exercise-induced fatigue,which are glycerolipid metabolism,glyoxylic and dicarboxylic metabolism,inositol phosphate metabolism,tricarboxylic acid cycle(TCA cycle)and glycerophospholipid metabolism.Compared with the TrnM group,after supplementing with ginsenoside Rh1,there are 3 different metabolites in the blood with large changes.There is a metabolic system that ginsenoside Rh1 influenced on exercise-induced fatigue,which is the tricarboxylic acid cycle.Conclusion: Ginsenoside Rh1 can significantly prolong the exhausting exercise time,reduce the generation of various metabolites during fatigue,enhance the ability of anti-oxidative damage,and significantly alleviate the symptoms of exercise-induced fatigue in rats by up-regulating the expression of GR protein in liver.In metabonomics,its mechanism involves the interaction of multiple metabolic pathways,and tricarboxylic acid cycle metabolic pathway plays an important role,which is of great significance in clinical application.