| Diabetes mellitus(DM),characterized by hyperglycemia,is a chronic metabolic disease which spreads at epidemic rates.The occurrence of diabetic complications presented to be the major causes of mortality in diabetic patients.Diabetic nephropathy(DN)is the most prevalent microvascular complication in DM,which commonly caused end-stage renal failure and contributd to high mortality.In current days,it is necessary to screen biomarkers and target for prevention and treatment of DN.Moreover,traditional Chinese medicines(TCM)have attracted much attention for their long time clinic test and reliable efficacy on prevention and treatment of diabetes and its complications.Radix Scutellariae(RS)and Gardenia jasminoides Ellis are two valuable TCM which have been comprehensively studied and applied for centuries in regard to DN.In the current study,an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)method integrated with statistical tools was applied to augment the understanding of obesity and DN.In addition,the therapeutic efficacy of RS and Gardenia jasminoides Ellis on DN were investigated.1.Metabolomics insights into diabetes nephropathy and protective effects of RSIn this study,streptozotocin-induced diabetic rats have developed markedly DN which was confirmed by biochemical and histological examinations.RS is one of the most commonly used TCM and has played an important role in treating DN.The therapeutic effects of RS in ameliorating renal lesions,kidney function and urinary metabolite abnormalities in rats with DN were presented.UHPLC-Q-TOF-MS based metabolomics approach was established to investigate the metabolic variations in urine and serum of diabetic rats which involved in the progression of DN.Multivariate analysis approaches were applied to differentiate the components between RS-treated group,model group and normal group.A series of urinary endogenous metabolites were screened for DN rats,suggesting metabolic dysfunction in pathways of tryptophan,phenylalanine,tyrosine,purine,pyrimidine,and energy metabolism.Treatment with RS could reverse urinary metabolite abnormalities,subsequently influenced the above disordered pathways,which were remarkably involved in inhibition of oxidative stress,inflammation and attenuation of several enzymes altered in DN.Our results thus provide an overall view of the progression of DN,and nephroprotective effects of RS against DN.2 Metabolomics study on the protective effects of Radix Scutellariae-Gardenia jasminoides couples(RG)on DN.DN rat model was established to explore the treatment effect of RG on DN.Biochemistry results showed that,RG could effectively control blood glucose level,attenuate lipid dysfunction and oxidative stress caused by DN.Moreover,UHPLC-Q-TOF-MS based urine and serum metabolomics approaches have been established to investigate the therapeutic effects of RG.These potential biomarkers involved in perturbations in tryptophan metabolism,phenylalanine metabolism,tyrosine metabolism,lipid metabolism and arachidonic acid metabolism pathways that closely related with oxidative stress and inflammation.RG intervention could effectively modulate these disturbed metabolism pathways,thereby,block the progression of DN.Based on identification of pathological metabolic changes,metabolomics pointed to potential targets for therapeutic effect of RG against DN.3.High throughput screening for glycogen phosphorylase(GPa)inhibitorIn metabolomics study on the protective effects of RS,we found several enzymes that involved in the potential treatment target of RS,including monoamine oxidase and GPa.Hence we assessed the potential GPa inhibited activity of RS extract,Gardenia jasminoides Ellis extract,and main active components in these two TCM.Flavones in RS extract exhibited high inhibitory activities.The structure-function relationships of these flavones were also discussed in the current study.These flavones were identified as the potential efficacy components in treatment of DN.4.Urine metabolomics of high-fat diet induced obesity.Obesity has become a global epidemic and public health challenge which associates with serious health issues including diabetes,cardiovascular disease,stroke,arthritis,and some types of cancer.To better understand obesity and obesity-related dysfunction,a high-fat diet(HFD)induced obese model was developed on Sprague-Dawley rats.Metabolomics based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)was untilized to identify and analyze obesity related metabolites in rat urine samples.Multivariate analyses were applied to differentiate metabolite patterns between HFD group and normal group.The study successfully identified 20 altered urine metabolites that correlated with obesity.These metabolites are mainly involved in tryptophan metabolism,phenylalanine and tyrosine metabolism,gut microbiota metabolism and insulin resistance related metabolism.They could serve as potential biomarkers to diagnose the development of obesity.In conclusion,an UHPLC-Q-TOF-MS method integrated with multivariate analysis was developed to gain the global profiling of the endogenous metabolites in obese and DN rats.Potential biomarkers were identified,which were involved in several metabolic pathways and would help on further understanding of the mechanism of obesity,DN and treatment effect of RS and RG.A high-throughput screening assay was established for identification of GPa inhibitors in RS and Gardenia jasminoides.To sum up,we illustrated the hypoglycemic mechanisms and the DM treated mechanisms of RS and Gardenia jasminoides,providing a foundation for developing new drugs in RS. |
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