Behavior and metabolomics study of the anti-aging effects of Scutellaria baicalensis Georgi extract on D-galactose-induced rats

OBJECTIVE Behavior research and urinary metabolomics method were applied to evaluate the anti-aging effects of Scutellaria baicalensis Georgi extract(SBG)in D-galactose-induced rats.METHODS Fifty rats were randomly divided into five groups(n=10in each group).Group 1served as vehicle control with injection of saline(vehicle control group),and the other groups of rats received daily subcutaneously injected with D-galactose(aged model group)at dose of 100mg·kg-1 for ten weeks,respectively.At the same time,rats in groups 3-5were intragastrically administered SBG 〔extracted twice with 60%(V/V)ethanol〕at doses of 50,100 and 200mg·kg-1 for ten weeks,and the rats of groups 1 and 2 were administrated an equal volume of the vehicle.At the tenth week,the learning and memory abilities were examined by Morris water maze.The urine was collected using metabolic cages and analyzed by high-resolution 1HNMR spectroscopy combined with multivariate statistical analyses.Principal component analysis(PCA)was utilized to classify and reveal the differences between the model group and control group.Then,the concentration of these differences was analyzed with t-test to determine whether SBG was possible to influence the metabolic pattern induced by D-galactose.RESULTS Compared with the vehicle control group,the D-galactose-treated aged model group markedly spent longer time(P<0.05)in finding the platform on days 3-5 in the spatial learning acquisition training of Morris water maze test.However,the escape latency was significantly reduced(P<0.05)by long-term administration of SBG(50,100 and 200mg·kg-1)compared with the D-galactose-treated aged model group on days 3-5.In the probe test,the D-galactose-treated aged model group made fewer(P<0.05)platform crossings and distance travelled in target quadrant(P<0.05)than the vehicle control group,and the SBG at doses of 50,100 and 200mg·kg-1 treatments groups could significantly increase(P<0.05)the number of times of crossing over the platform site.The SBG at doses of100 and 200mg·kg-1 treatments groups could significantly increase(P<0.05)the distance travelled in target quadrant compared with the D-galactose-treated aged model group.In addition,the significant difference in metabolic profiling was observed from model group compared with drug-dose group by using PCA,indicating the recovery effect of SBG on D-galactose induced aging rats.Some significantly changed metabolites like glycine,glucose and hexadecanoic acid have been identified.These biochemical changes are related to the the disturbance in aimno acid metabolism,energy metabolism and glycometabolism,which are helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.CONCLUSION These results demonstrate that SBG extract has protective effect on the D-galactose-induced aging in rats.

1^H NMR-based metabolomics approach to investigating the renal protective effects of Genipin in diabetic rats

Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance(NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.

Metabolomics coupled with similarity analysis advances the elucidation of the cold/hot properties of traditional Chinese medicines

It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine(TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance(NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs.

Mechanisms of Chinese medical formula Fangji Huangqi Decoction as an effective treatment of nephrotic syndrome based on systems pharmacology

Objective: With the development of the society, the number of people who catch the nephrotic syndrome(NS) is going up roughly. As we all know, traditional Chinese medicine(TCM), especially Fangji Huangqi Decoction(FHD), has a long history with good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated.Methods: In this study, TCMSP platform was employed to screen active compounds of each herb of Fangji Huangqi Decoction combined with literatures. Furthermore, PharmMapper and SEA were used to predict and screen the active targets of FHD, and the HOME-NCBI-GENE, GeneCards and OMIM database were used to screen the active targets of NS. The GO and KEGG pathways involved in the targets were analyzed by Clue GO. Finally, contribution index was used to screen the active ingredients of FHD in the treatment of NS.Results: After drug-likeness(DL) and bioavailability(OB) filtering, 43 compounds were selected from FHD,interacting with 85 NS-related targets. Systematic analysis of the constructed networks revealed that it was mainly involved in PI3 K-Akt signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway and TNF signaling pathway. The contribution index of every active ingredient also indicated five compounds, including astragaloside IV, quercetin, glycyrrhizic acid, glycyrrhizin and fangchinoline.Conclusions: These results have successfully predicted the pharmacodynamic material basis and the mechanism efficiency of FHD in the treatment of NS.

Investigation on Endogenous Metabolites in Pancreas of Diabetic Rats after Treatment by Genipin through^1H-NMR-based Metabolomic Profiles

Objective To investigate the change rules of endogenous metabolites in pancreas of the diabetic rats, and to explore the mechanism of genipin treatment for diabetes rats. Methods Metabolomic method based on ^1H-NMR was applied, the diabetic rat model was prepared by ip injecting alloxan, and the high-, mid-, and low-dose genipin or metformin hydrochloride was ig injected as well as the rats in control and model groups were given the same volume of normal saline for 2 weeks. The pancreases of rats were collected and ^1H-NMR test was conducted, the metabolomic technology was adopted to analyze the endogenous metabolite changes in pancreas. Results The high-dose genipin possessed a better hypoglycemic effect, which could increase the contents of isoleucine, phosphatidylcholine, and phosphatidylethanolamine, and significantly reduce the contents of lactic acid, alanine, glutamine, aspartic acid, and creatine in pancreas of diabetic rats. Conclusion This study provided a theoretical basis for further exploration on the pathogenesis of diabetes and the mechanism of genipin for treatment of diabetes.