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.

3种代谢综合征工作定义在男性健康体检者中的比较

目的:比较1999年WHO, 2001年美国第三次胆固醇教育计划(NECP ATPIII)及2003年中华医学会糖尿病学会(CDS)提出的3种代谢综合征(MS)工作定义在同一健康体检人群中检出的异同。方法:在739例男性健康体检人群中分别应用上述3种工作定义诊断MS,比较MS患病率,分析各定义诊断MS的一致性及临床特点结果:WHO( 1999 ),ATPIII( 2001 )及CDS( 2003 )MS工作定义诊断的MS标化患病率分别为36. 9%, 11. 8%21. 0%。3种定义对MS总的诊断符合率为68. 6%。WHO定义与ATPIII定义、CDS定义的诊断符合率分别为72. 5%, 81. 2%; ATPIII定义与CDS定义符合率为83. 5%。WHO定义的各组分中胰岛素抵抗患病率最高(标化率为49. 4% );ATPIII定义中高血压患病率最高(标化率为48. 5% ),腹型肥胖患病率最低(标化率为1. 87% );CD定义中肥胖患病率最高(标化率为63. 3% )。3种定义检出的MS组的空腹胰岛素水平及HOMA IR均高于其相应的非MS组。结论: 3种定义具有较高的诊断符合率,但对同一人群的应用仍存在差异,提示制定国内外统一的诊断定义势在必行。

Ganoderma lucidum polysaccharide peptide alleviates hepatoteatosis via modulating bile acid metabolism dependent on FXR-SHP/FGF

OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP)is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×10^5,which ratio of polysaccharide to peptide is approximately 95%/5%.The purpose of this study was to determine whether GLPP has therapeutic effect on Non-alcoholic fatty liver disease(NAFLD).METHODS Ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophos⁃pholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a ther⁃apeutic drug for NAFLD.

基于拟靶向液相色谱-质谱联用的胃癌患者血清代谢组分析

胃癌是一种高发的恶性肿瘤,是癌症相关死亡的第二大病因。早期筛查是提高患者生存率的有效手段,但目前临床上尚缺乏实现胃癌无创筛检的可靠标志物。本研究采用了基于液相色谱-质谱联用的拟靶向代谢组学方法分析了20例胃癌患者及40例正常人血清代谢组,以期发现新的潜在代谢标志物。代谢组数据的主成分分析和偏最小二乘法数据分析结果显示,胃癌患者与健康人群的血清代谢组存在明显的差异,结合非参数检验进一步筛选并定性出57个差异代谢物。其中二氢胆固醇经验证组样本验证,具有成为胃癌代谢标志物的潜力。本研究在发现胃癌的潜在代谢标志物的同时,也为胃癌患者代谢分型提供了重要的科学依据。