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1.
Depression is a major cause of illness and disability. We applied untargeted metabolomics using mass spectrometry to identify metabolic signatures associated with depression in serum and explored the antidepressant effects of lilies and Rhizoma Anemarrhenae on an experimental model of chronic unpredictable mild stress (CUMS). Meanwhile metabolomics based on UHPLC‐Q‐TOF‐MS was used to study the change in metabolites in CUMS rat serum and to evaluate the effects of Rhizoma Anemarrhenae and lilies (alone and in combination). Partial least squares‐discriminant analysis identified 30 metabolites as decisive marker compounds that discriminated the CUMS rats and the control rats. The majority of these metabolites were involved in amino acid metabolism, the tricarboxylic acid cycle, and phosphoglyceride metabolism. The reliability of the metabolites was evaluated by the administration of lilies, Rhizoma Anemarrhenae, fluoxetine and the combination of lilies and Rhizoma Anemarrhenae to the CUMS rats. Behavior studies demonstrated that treatment with the combination of lilies and Rhizoma Anemarrhenae resulted in optimal antidepressant effects. The combination treatment was almost as effective as fluoxetine. Our results suggest that lilies and Rhizoma Anemarrhenae demonstrate synergistically antidepressant effects in CUMS via the regulation of multiple metabolic pathways. These findings provide insight into the pathophysiological mechanisms underlying CUMS and suggest innovative and effective treatments for this disorder.  相似文献   

2.
Zhou  Yu-Zhi  Zheng  Xing-Yu  Liu  Xiao-Jie  Li  Zhen-Yu  Gao  Xiao-Xia  Sun  Hai-Feng  Zhang  Li-Zeng  Guo  Xiao-Qing  Du  Guan-Hua  Qin  Xue-Mei 《Chromatographia》2012,75(3-4):157-164

Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. In this study, we investigated the metabolic profiling of urine samples from chronic unpredictable mild stress (CUMS) rats to find potential disease biomarkers and research pathology of depression. Metabolome in urine was analyzed using gas chromatography/mass spectrometry (GC/MS) in conjunction with multivariate statistical techniques. The urine samples of male Sprague–Dawley rats were collected at different time points and then were derivatized by methoximation/silylation. Clear separation between the model and control group was achieved, and 15 metabolites were identified, which suggested that the depressed state may be related to neurotransmitter, energy metabolism and immunity. The time-dependent trajectory of metabolites pattern revealed that the maximum biochemical change happened on the 21st day, which was consistent with the results of behavior tests. The study suggested that the metabonomic approach could be used as a potentially powerful tool to investigate the biochemical change in certain physiopathological conditions, such as depression, as an early diagnostic means.

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3.
An ultra fast liquid chromatography coupled with IT-TOF mass spectrometry (UFLC/MS-IT-TOF) metabonomic approach was employed to study the plasma and urine metabolic profiling of atherosclerosis rats. Acquired data were subjected to principal component analysis (PCA) for differentiating the atherosclerosis and the control groups. Potential biomarkers were screened by using S-plot and were identified by the accurate mass and MSn fragments information obtained from UFLC/MS-IT-TOF analysis. 12 metabolites in rat plasma and 8 metabolites in urine were identified as potential biomarkers. Concentrations of leucine, phenylalanine, tryptophan, acetylcarnitine, butyrylcarnitine, propionylcarnitine and spermine in plasma and 3-O-methyl-dopa, ethyl N2-acetyl-l-argininate, leucylproline, glucuronate, t6A N(6)-(N-threonylcarbonyl)-adenosine and methyl-hippuric acid in urine decreased in atherosclerosis rats. Ursodeoxycholic acid, chenodeoxycholic acid, LPC (C16:0), LPC (C18:0) and LPC (C18:1) in plasma and hippuric acid in urine were in higher levels in atherosclerosis rats. The alterated metabolites demonstrated abnormal metabolism of phenylalanine, tryptophan, bile acids and amino acids. This research proved that metabonomics is a promising tool for disease research.  相似文献   

4.
运用代谢组学方法研究四氯化碳(CCl4)致小鼠肝损及水飞蓟宾肝保护作用的机理. 通过气相色谱-质谱(GC-MS)技术分析CCl4及水飞蓟宾作用下的小鼠肝组织匀浆及血浆代谢物谱. 使用正交偏最小二乘判别分析法研究正常组与CCl4模型组之间的代谢物谱差异, 并通过变量重要性投影(VIP)选取肝组织与血浆中各12种标志性代谢物. 使用主成分分析法研究水飞蓟宾预防性及治疗性给药对CCl4肝损的干预效果. 通过比较选取的标志性代谢物的含量的差异, 探讨了水飞蓟宾对CCl4致小鼠肝损的保护机理. 结果表明, CCl4作用后, 小鼠机体能量代谢、氨基酸代谢及脂类代谢都受到不同程度的影响. 水飞蓟宾能有效地缓解CCl4所造成的体内线粒体功能及氨基酸代谢紊乱. 采用代谢组学方法能较全面地反应生物体的生理及代谢状态, 并可应用于物质毒性和药效评价研究.  相似文献   

5.
采用盐酸肾上腺素加冰水浴建立急性血瘀大鼠模型,使用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)检测空白对照组与血瘀模型组中血浆代谢物,用主成分分析(PCA)、有监督偏最小二乘法判别分析(PLS-DA)及正交偏最小二乘法判别分析(OPLS-DA)对代谢组学数据进行多维统计分析,筛选潜在生物标志物。与对照组相比,在血瘀模型组大鼠血浆中检测出46个差异代谢物,血瘀模型组中乙酰胆碱、N6,N6,N6-三甲基-L-赖氨酸、胞嘧啶、乙酰肉碱等21个代谢物显著上调,吲哚丙酸、LysoPC(14:0)等25个代谢物显著下调,可能与脂质代谢、半乳糖代谢、亚油酸代谢、不饱和脂肪酸生物合成、糖酵解、花生四烯酸代谢等通路有关。代谢产物可作为血瘀证研究中的重要标记物,该研究结果有助于揭示血瘀证的发病机制,可为临床血瘀疾病的诊断及选用药物治疗提供思路,为后续治疗手段提供参考依据。  相似文献   

6.
黄芪黄酮干预脾虚水湿不化大鼠血浆代谢组学研究   总被引:1,自引:0,他引:1  
采用高效液相色谱结合飞行时间质谱检测正常大鼠、脾虚水湿不化证大鼠及黄芪黄酮组分干预后大鼠血浆内源性代谢物变化,获取大鼠血浆代谢图谱,研究黄芪黄酮组分干预脾虚水湿不化证的作用机制.采用高脂低蛋白饮食加负重游泳力竭建立脾虚水湿不化证大鼠模型,选择Halo C18色谱柱,流动相为0.05%甲酸-水与0.05%甲酸-乙腈,梯度洗脱,利用液相色谱-串联质谱分析测定大鼠血浆样品.利用主成分分析法对造模前后大鼠血浆样本进行代谢轮廓分析,结合变量投影重要性及显著性分析等筛选对分组贡献最大的差异标志物及相关通路,阐明药物的作用机制.结果表明, 黄芪黄酮组代谢轮廓异于模型组,而接近于正常组,共鉴定出了包含甘油磷脂类、鞘酯类、氨基酸类等在内的11种潜在生物标志物,其代谢通路包括三羧酸循环、甘油磷脂代谢、脂肪酸代谢及氨基酸代谢等,主要涉及体内能量代谢和脂肪代谢.黄芪黄酮干预脾虚水湿不化证大鼠后, 宏观指标(如体重、自主活动)和微观指标(如代谢标志物、血脂)均明显回调,表明黄芪黄酮可能主要通过调节能量代谢、脂肪代谢等途径而发挥健脾利水作用.  相似文献   

7.
《Analytical letters》2012,45(14):2406-2416
In recent years, more sensitive and less invasive methods for detecting organ transplantation rejection have been receiving increasing interest. Metabonomics is a recent development in the transplantation field. In this paper, a metabonomic investigation on plasma samples of liver transplanted rats was presented. Samples from control, syngeneic, and allogeneic transplanted groups were analyzed using GC-MS after derivatization. Thirty-six metabolites in the acquired GC-MS data, including amino acids, organic acids, carbohydrates, and some other metabolites were identified and matched by NIST spectral library. The scores plot of principal component analysis (PCA) showed that the three groups were unambiguously apart from each other; the syngeneic liver transplanted group and the control group were adjacent, indicating a high similarity between the two groups; the allogeneic liver transplanted group, however, was apparently separate from the other two groups, demonstrating the significant differences of metabonomic profiles among the groups with or without immunologic reaction. Among the identified thirty-six metabolites, galactose, D-glucose, L-deoxyglucose, gulose, cholesterol, urea, and L-aspartic acid were found to be the significantly changed metabolites according to PCA loadings plot. In the allogeneic liver transplanted group, levels of cholesterol, urea, and L-aspartic acid increased but galactose, D-glucose, L-deoxyglucose, and gulose levels declined compared to those in the control and the syngeneic liver transplanted groups.  相似文献   

8.
采用超高效液相色谱-四极杆-静电场轨道阱质谱(UHPLC-Q-OrbitrapHRMS)技术对胶质瘤患者和正常对照人群的血浆进行代谢轮廓分析,筛选胶质瘤代谢标志物,为其发病机制阐明和临床早期诊断提供科学依据。通过对UHPLC-Q-OrbitrapHRMS采集得到的谱图进行峰识别、峰匹配和去噪等处理后,应用主成分和正交偏最小二乘-判别分析法对代谢组学数据进行统计分析,筛选VIP1.0及P0.05的差异代谢物,并进一步对其诊断能力进行评价。结果显示,胶质瘤患者的血浆代谢轮廓发生明显变化,发现并鉴定得到10个差异代谢物,其中亮氨酸、缬氨酸、色氨酸、胆碱和牛磺酸在胶质瘤患者血浆中含量降低,组氨酸、柠檬酸、乳酸、肌酸和丙酮酸含量升高,与正常对照组比较具有显著性差异(P0.05),提示氨基酸和能量等代谢异常可能对胶质瘤的发生发展具有重要影响。此外,各差异性代谢物对胶质瘤均显示出较好的诊断能力(AUC0.8),可作为潜在诊断标志物。  相似文献   

9.
We have developed a metabolic flux analysis method that is based on (13)C-labeling patterns of the intracellular metabolites directly measured by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The flux distribution of the central carbon metabolism in Escherichia coli was determined by this new approach and the results were compared with findings obtained by conventional GC-MS analysis based on isotopomer of the proteinogenic amino acids. There were some differences in estimation results between new approach using CE-TOFMS and conventional approach using GC-MS. These were thought to be attributable to variations in measured mass distributions between amino acids and the corresponding precursors and to differences in the sensitivity of the exchange coefficients to mass distributions. However, our CE-TOFMS method facilitates high-throughput flux analysis without requiring complicated sample preparation such as hydrolysis of proteins and derivatization of amino acids.  相似文献   

10.
Semen descurainiae oil (SDO) is an important traditional Chinese medicine that was recently discovered to have the function of reducing blood lipids. Metabolomics analyses of plasma, liver and kidney in rats were performed using 1H‐NMR and LC–MS to illuminate the lower blood lipid concentration effect of SDO, and niacin was considered as the active control. The measure of total cholesterol (TC) and low‐density‐lipoprotein cholesterol (LDL‐C) in plasma showed that SDO treatment decreased significantly the content of TC and LDL‐C. An orthogonal partial least squares–discriminant analysis approach was applied to identify the different metabolic profiles of plasma, liver and kidney in rats and to detect related potential biomarkers. The results suggested that the metabolic profiles of the control group and hyperlipidemia group showed significant difference and the SDO and niacin group had effective anti‐hyperlipidemia function. The biomarkers primarily concern lipid metabolism, amino acid metabolism and glycometabolism, and the change in biomarkers indicated that hyperlipidemia could cause the unbalance of these metabolic pathways in vivo. SDO reduced blood lipids by repairing amino acid and lipid metabolism.  相似文献   

11.
欧阳瑒  迟磊  徐超  赵欣捷  崔振泽 《色谱》2021,39(3):281-290
呼吸道合胞病毒(RSV)容易引发下呼吸道感染,尤其是小儿毛细支气管炎。中药定喘汤用于RSV感染的治疗在中国有着广泛的临床实践基础。由于中药体系的复杂性,其治疗机制和主要药效成分还不够明确。采用代谢组学方法分析中药药效,可以为传统中药治疗提供现代科学论证。该研究对大鼠各干预组分别采用中药定喘汤全方,宣、降、清分解剂以及利巴韦林灌胃治疗,正常组大鼠和RSV模型组大鼠均采用生理盐水灌胃。分别取大鼠在第0、3、7天的眼底血浆进行基于液相色谱-串联质谱法的非靶向代谢组学分析,以研究RSV感染引起的代谢组改变、定喘汤对RSV感染相关代谢物的调控及定喘汤的主要药效来源。对检测的代谢物离子进行多变量分析,建立主成分分析模型,结果显示在RSV感染及治疗进程中,中药定喘汤组与利巴韦林阳性对照组对RSV感染大鼠产生的总体代谢调控效果类似。在3种定喘汤分解剂中,组成成分为麻黄和白果的宣法分解剂对代谢组的调控作用与定喘汤更为接近,可能为定喘汤的主要药效来源。基于配对t检验发现大鼠在感染RSV后有83种代谢物发生了显著性改变,表明RSV感染可造成大鼠多条代谢通路紊乱。第3天时中药定喘汤对包括胆汁酸、氨基酸、有机酸、脂质等在内的代谢物有治疗效果。3种分解剂中,宣法分解剂对代谢物的调节作用与定喘汤类似,而降法分解剂和清法分解剂对大鼠因感染RSV引起的酰基肉碱的异常升高有明显下调作用。各组都有维持肠道菌群和免疫系统稳定的药效。该研究采用代谢组学方法评价定喘汤的药效,发现了定喘汤治疗后改变的代谢物的种类及变化规律,为定喘汤的治疗机理和活性成分的研究提供了理论支持。  相似文献   

12.
Abstract

Poria cocos is an edible medicinal mushroom with the effects of inducing diuresis, excreting dampness, invigorating the spleen and tranquilizing the mind. The triterpenoids of Poria cocos as the main active ingredients have shown health benefits of the central nervous system of the human body. Accordingly, this study aimed at further understanding the antidepressant-like effect and a potential mechanism of the triterpenoids extracts from Poria cocos (TPC). As a result, the TPC significantly ameliorated depression-like behaviors on chronic unpredictable mild stress (CUMS) rats, and restored the levels of brain-derived neurotrophic factor and nerve growth factor in the hippocampus of rats. Gut microiota analysis revealed that TPC could increase the biodiversity and markedly regulate the relative abundance of [Prevotella], Allobaculum and Ochrobactrum of CUMS rats. The cecal contents metabolomics pointed to thirteen biomarkers associated with TPC antidepressant effect, which involved in primary bile acid biosynthesis, taurine and hypotaurine metabolism, arginine and proline metabolism. Correlation analysis further showed that there was a strong correlation relationship between the gut microbiota and the cecal contents metabolites, especially compounds involved in energy metabolism, inflammation and immunity. In conclusion, TPC showed a potential antidepressant effect, which was possibly mediated the gut microbiota and cecal contents metabolism.  相似文献   

13.
利用代谢组学技术研究全氟辛酸的人肝脏毒性机制   总被引:3,自引:0,他引:3  
Peng S  Yan L  Zhang J  Shen H 《色谱》2012,30(2):123-127
采用超高效液相色谱-飞行时间质谱联用系统研究暴露于不同浓度全氟辛酸(PFOA)72 h的正常人L-02肝细胞内代谢谱的变化。将主成分分析法用于数据分析和生物标志物的初步筛选。在正离子和负离子扫描模式下,对照组和暴露组均可得到较好区分并呈现出明显的剂量-效应关系,筛选鉴定了18种与全氟辛酸毒性密切相关的潜在生物标志物,包括肉碱和酰肉碱、核苷及其同源物、氨基酸及其同源物等。在暴露组中,在脂肪酸代谢中起关键作用的肉碱类代谢物的含量变化显著,其中肉碱含量随剂量的升高呈现明显的下降趋势,而酰肉碱则呈现相反的变化趋势,表明全氟辛酸可通过诱导胆固醇等脂类物质代谢相关基因的异常表达从而扰乱胆碱类物质的正常合成和代谢。除了变化最显著的胆碱代谢通路之外,全氟辛酸的肝脏毒性还与三羧酸循环、嘌呤代谢、氨基酸代谢和核酸代谢等多个通路相关。这些结果表明,PFOA在体内经过长时间累积可通过干扰众多的代谢通路从而破坏人体的正常生理机能,造成潜在的健康危害。  相似文献   

14.
A metabolomic investigation of intoxication with Aconitum sp. alkaloids was carried out. Plasma obtained from Wistar rats administered these alkaloids was analyzed using gas chromatography/time‐of‐flight mass spectrometry. Samples were analyzed following protein precipitation, liquid‐liquid extraction, and derivatization. Thirty‐six metabolites were identified among the detected compounds. Subsequent data analysis using the t test and principal component analysis revealed metabolic differences between the control rats and treated groups as well as between the groups of rats administered different alkaloids. Twenty‐seven metabolites were significantly different between plasma samples from the controls and treated groups. The significant decreased plasma levels of glutamine and creatinine in all treated groups suggested impaired heart and muscle function caused by alkaloids. The plasma levels of 22 metabolites in the hypaconitine group were significantly decreased. In contrast, only 8 and 13 metabolites were observed with significantly decreased levels in the aconitine and mesaconitine groups, respectively.These results indicated that Aconitum sp. alkaloids can cause metabolic disorders in rats. The toxicity and corresponding mechanism of hypaconitine was different from those of aconitine and mesaconitine, based on the differences of perturbed metabolic patterns between groups. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

15.
Shallot landraces and varieties are considered an important genetic resource for Allium breeding due to their high contents of several functional metabolites. Aiming to provide new genetic materials for the development of a novel bulb onion cultivar derived from intraspecific hybrids with useful agronomic traits from shallots, the metabolic profiles in the bulbs of 8 Indonesian shallot landraces and 7 short-day and 3 long-day bulb onion cultivars were established using LC–Q-TOF-MS/MS. Principal component analysis, partial least squares discriminant analysis, and dendrogram clustering analysis showed two major groups; group I contained all shallot landraces and group II contained all bulb onion cultivars, indicating that shallots exhibited a distinct metabolic profile in comparison with bulb onions. Variable importance in the projection and Spearman’s rank correlation indicated that free and conjugated amino acids, flavonoids (especially metabolites having flavonol aglycone), and anthocyanins, as well as organic acids, were among the top metabolite variables that were highly associated with shallot landraces. The absolute quantification of 21 amino acids using conventional HPLC analysis showed high contents in shallots rather than in bulb onions. The present study indicated that shallots reprogrammed their metabolism toward a high accumulation of amino acids and flavonoids as an adaptive mechanism in extremely hot tropical environments.  相似文献   

16.
The awareness, treatment, and control rates of hypertension for young adults are much lower than average. It is urgently needed to explore the variances of metabolic profiles for early diagnosis and treatment of hypertension. In current study, we applied a GC–MS based metabolomics platform coupled with a network approach to analyze plasma samples from young hypertensive men and age-matched healthy controls. Our findings confirmed distinct metabolic footprints of young hypertensive men. The significantly altered metabolites between two groups were enriched for the biological module of amino acids biosynthesis. The correlations of GC–MS metabolomics data were then visualized as networks based on Pearson correlation coefficient (threshold = 0.6). The plasma metabolites identified by GC–MS and the significantly altered metabolites (P < 0.05) between patients and controls were respectively included as nodes of a network. Statistical and topological characteristics of the networks were studied in detail. A few amino acids, glycine, lysine, and cystine, were screened as hub metabolites with higher values of degree (k), and also obtained highest scores of three centrality indices. The short average path lengths and high clustering coefficients of the networks revealed a small-world property, indicating that variances of these amino acids have a major impact on the metabolic change in young hypertensive men. These results suggested that disorders of amino acid metabolism might play an important role in predisposing young men to developing hypertension. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism underlying complex diseases.  相似文献   

17.
汤新星  顾源  蔡尚  徐美玲  王畅 《色谱》2012,30(7):696-704
建立了基于高效液相色谱-电喷雾串联质谱(HPLC-ESI MS/MS)与固相萃取(SPE)相结合的大鼠血浆中氨基酸的分析方法。以硅胶基质的强阳离子交换固相萃取柱(SCX-SPE)提取血浆中的氨基酸和降低基质效应,HPLC-ESI MS/MS进行测定。对SPE处理的样品pH值进行了优化,发现pH 2.8时SCX-SPE提取氨基酸的回收率和重现性比较令人满意。除赖氨酸和鸟氨酸外,氨基酸的总体回收率在33.6%~107.7%之间;除精氨酸外,氨基酸标准曲线的线性相关系数r2>0.99; 25种氨基酸测定的日内精密度和日间精密度较好,相对标准偏差(RSD)分别低于9.0%和19.1%。此外,将该分析方法用于电离辐射对大鼠血浆氨基酸代谢的影响研究。结果表明,辐射可导致血浆中氨基酸代谢紊乱,并且其紊乱程度与电离辐射损伤程度正相关。研究结果为筛选新的急性辐射损伤标记物研究提供了实验依据。  相似文献   

18.
Chronic unpredictable mild stress (CUMS) is a well‐validated model of depression. In this study, a urinary metabonomics method based on the NMR spectrometry was used to study the metabolic perturbation in CUMS‐induced rat depression model. With pattern recognition analysis, a clear separation of CUMS rats and healthy controls was achieved, and nine endogenous metabolites contributing to the separation were identified. CUMS‐treated rats were characterized by the increase of glycine, pyruvate, glutamine, and asparagines, as well as the decrease of 2‐oxoglutarate, dimethylglycine, citrate, succinate, and acetate. The urinary biochemical changes related to the metabolic disturbance in CUMS induced depression, and the possible correlations with live qi stagnation in traditional Chinese medicine are discussed. The work shows that CUMS is a reliable model for studying depression, and the noninvasive urinary metabolomic method is a valuable tool to investigate the biochemical pertubations in depression as an early diagnostic means. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

19.
Melissa officinalis contains various secondary metabolites that have health benefits. Generally, irradiating plants with ultraviolet (UV)-B induces the accumulation of secondary metabolites in plants. To understand the effect of UV-B irradiation on the metabolism of M. officinalis, metabolomics based on gas chromatography-mass spectrometry (GC-MS) was used in this study. The GC-MS analysis revealed 37 identified metabolites from various chemical classes, including alcohols, amino acids, inorganic acids, organic acids, and sugars. The metabolite profiles of the groups of M. officinalis irradiated with UV-B were separated and differentiated according to their irradiation times (i.e., 0, 1, and 2 h), using principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The PCA score plots of PC1 and PC2 showed that the three groups with different irradiation times followed a certain trajectory with increasing UV-B irradiation. HCA revealed that metabolic patterns differed among the three groups, and the 1 h-irradiated group was more similar to the control group (0 h) than the 2 h-irradiated group. In particular, UV-B irradiation of plants led to a decrease in sugars such as fructose, galactose, sucrose, and trehalose and an increase in metabolites in the tricarboxylic acid cycle, the proline-linked pentose phosphate pathway, and the phenylpropanoid pathway. This study demonstrated that metabolite profiling with GC-MS is useful for gaining a holistic understanding of UV-induced changes in plant metabolism.  相似文献   

20.
以高场核磁共振技术为研究手段,通过分析腹腔注射0.2、2、10、20mg/kg体重剂量的La(NO3)3后大鼠尿液中代谢物浓度、物种的变化,研究了稀土化合物在动物体内的作用情况,结果表明,稀土的引入使动物肾脏和肝脏都受到一定程度的损伤,并在代谢物中挑选出了合适的NMR markers,其变化可以反映稀土离子作用后大鼠的异常代谢。  相似文献   

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