| Ethnopharmacology:Aging is characterized as an inevitable degenerative changes of the body tissues and organs functions.As global aging process is speeding up,the ill health result from aging and age-related diseases are becoming more and more serious,preventing or delaying the pathogenesis of aging has become the current hot issue in the gerontology.So far the anti-aging medicine includes traditional chinese medicine and modern medicine.While the side effects of modern drugs frequently occur,the application of natural products,including traditional Chinese medicine and herbal medicine,is more and more extensive.Scutellaria baicalensis Georgi(SBG),as a traditional Chinese herbal medicine,possess pharmacological effects such as antioxidative,anti-inflammatory and anti-cancer.In recent years,SBG have shown anti-aging activity C.elegans and rodents,but the research is very limited.Metabonomics is an important platform of systems biology,with the integrity and systemic feature.In this study,an 1H NMR based metabolomic approach was applied to evaluate the aging and the effects of anti-aging drugs,which has shed new light on the pathophysiology of aging and the mechanism of therapeutic effect of drugs.OBJECTIVE:The aim of this study is to systematilly analysis of metabolic characteristics of D-galactose induced aging rats,explore the anti-aging mechanism of SBG.METHODS:1 A rats aging model was induced by injecting subcutaneously D-galactose(100 mg/kg)for ten weeks.The anti-aging activity of SBG was evaluate by various methods,including behavior test,biochemical parameters,and pathological changes.2 1H NMR techniques combined with multivariate statistical analysis was used to detect the change of urine metabolic fingerprinting of D-galactose induced aging rats at different time.At the end of 10 weeks,the urine metabolic fingerprinting of aging rats was analysis,and find potential biomarkers of aging.The regulation effects of SBG on biomarkers in urine was discussed.3 1H NMR techniques was applied to analysis the metabolic signature of aging in the serum metabolome and identify the aging-related biomarker.The regulation effect of SBG on biomarker was evaluated.4 The liver was chosen as the representative organ to investigate the anti-aging effect of SBG on organ.The metabolic signature of aging in the metabolome was analyzed.With the help of metabolic network analysis,the possible mechanism of SBG on aging rats was elucidated.Results:1 Behavior test,biochemical and histopathology results showed that the aging animal model was successfully reproduced.SBG(100mg/kg and 200mg/kg)can ameliorate cognitive impairment,while SBG(200mg/kg)significantly attenuate oxidative stress and pathological changes of hippocampus.2 The urine metabolic fingerprinting at 2,4,6,8,10 weeks was analyzed.The results demonstrated that no separation between model and control group on week 2 and 4.The difference increased over time.Following 10 weeks of D-galactose treatment,a clear separation between model and control group was observed.It provides a scientific basis for the establishment of the aging model induced by D-galactose(100mg/kg).8 endogenous urinary metabolites including citrate,pyruvate,lactate,TMA,pantothenate,(3-hydroxybutyrate,a-ketoglutarate contributing to the separation were identified.The level of pyruvate,lactate,pantothenate and citrate was reverse in low dose SBG group.The high SBG group significantly regulated citrate,pyruvate,lactate,TMA,pantothenate,?-hydroxybutyrate showing a tendency of recovering to control group.3 The results of serum metabolomics show that pyruvate,lactate,choline,isoleucine,alanine,betaine,methionine,acetone and acetate are aging-related biomarker,the low dose SBG group regulated the level of pyruvate,lactate and methionine,The high SBG group significantly regulated pyruvate,lactate,choline,isoleucine,alanine,betaine and methionine showing a tendency of recovering to control group,These biochemical changes are related to the the disturbance in energy metabolism,lipid metabolism,and amino acid metabolism.4 The results of liver metabolic study by NMR showed that the level of lactate,choline,isoleucine,GSSG,leucine,inosine,valine,glycine,citrate and glutamate were significantly changed in model group compared with the control group.The biomarker of lactate,choline,isoleucine,GSSG,leucine,valine,glycine,citrate and glutamate were significantly regulated in SBG group,which involved in energy metabolism and amino acid metabolism.Conclusion:An aging model induced by daily D-galactose s.c injection for 10 weeks was successfully reproduced.SBG can attenuate oxidative stresses as well as learning dysfunction in aging rats.Its action mechanism is closely correlated with improvement of energy metabolism,lipid metabolism,and amino acid metabolism. |
PDF Full Text Request