Metabonomics-based methods for metabolic disease:research advances / 国际药学研究杂志

As a new technology of 'omics', m etabonomics is a comprehensive tool employed to investigate the metabolic response of living systems to endogenous and exogenous stimuli. It can link phenotypes with the changes at molecular level, which is helpful to uncovering the metabolic changes during the development of disease and to explore the possible pathogenesis. With the change of diet and living habits, the incidences of metabolic diseases such as hypertension and diabetes are increasing, seriously affecting people′s health and safety, so it is important to explore the pathogenesis as an assistant way of clinical diagnosis and treatment. Recently, the study of various metabolic diseases has achieved a certain progress. This paper gives a brief introduction to metabonomics and an overview of the latest progress in metabonomics applied in the study of metabolic diseases such as obesity, diabetes, hypertension, hyperlipidemia and metabolic syndrome.

Metabonomics analysis of effects induced by PCBs and high fat diet combined expo-sure in SD rats / 军事医学

Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners( PCBs) and high fat diet alone or in combination.Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet.Urine samples were collected after 6-week treatment, 1 H NMR spectra were performed and analyzed by principal component analysis ( PCA) . Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism.The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide ( TMAO) in the combined exposure group after six-week exposure.Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle (TAC).These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids.The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.

Progress in the application of metabonomics technology in toxicology research / 国际药学研究杂志

Metabonomics is a new member in the omics field following the development of genomics, transcriptomics and proteomics, with its research object being the collection of metabolites-metabolome, the downstream products of life. Even with the development of past decade, there are still many problems to be solved in the area of experimental techniques, data analysis and results annotation. Any xenobiotics would cause the disturbance of homeostasis of organisms, resulting in the changes of metabolites. Consequently, toxicology is one of the major application areas of metabolomics, and is the earliest one. Metabolomics has been widely used in the early toxicological screening of leads, preclinical and clinical toxicology of drugs in animals and human, as well as in surrogate models such as cell lines and zebrafish. Annotation techniques for metabolic data have also been developed. In this paper, the development of metabolomic techniques and its application in toxicology are reviewed.

Serum metabolic profiles among different geographical populations / 军事医学

Objective To investigate the effect of geographical differences on human serum metabolic profiles .Methods A total of 169 serum samples were collected from healthy individuals from 9 provinces in China and divided into four groups according to the geographical location .The nuclear magnetic resonance ( NMR) data of these samples were segmentally inte-grated, normalized,and analyzed with multivariate statistical methods using SIMCA-P 10.0 software to investigate the differ-ence in serum metabolites between eastern and western populations or between northern and southern populations .Results There were differences in a variety of small molecule metabolites in serum between eastern and western populations or be -tween northern and southern,including glucose,lipoproteins,amino acids,ketones,creatine and choline.Conclusion The geographical differences in a variety of factors (temperature,precipitation,folk culture, living habits,etc) result in the differences in human serum metabolic profiles ,which can provide appropriate reference for epidemiological studies and nu -tritional metabonomics .

NMR-spectroscopy-based metabonomic approach to analysis of Siwutang, a novel prescription, treated blood deficiency in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To discover the characteristic changes of metabolic profiles in C57 mice with cyclophosphamide induced blood deficiency and the effect of Siwutang.</p><p><b>METHOD</b>An integrated metabonomic study using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy has been applied to investigate the metabolic profiles of serum, aqueous and lipidic extracts of thoracic gland, spleen, bone marrow obtained from control, model group (intraperitoneal injection of cyclophosphamide at a dose of 250 mg x kg(-1)) and Siwutang treated model group. The NMR spectra were integrated in segments of 0.04 ppm and then analyzed by principal component analysis (PCA) using SIMCA-P software to visualize the similarities and differences in metabolic profiles between these groups.</p><p><b>RESULT</b>PCA result showed conspicuous difference in the metabolic profiles between groups. Compared with the control group, the model group contained lower concentration of lactate, 3-hydroxybutyrate, choline, glucose, and higher concentration of VLDL/LDL, leucine/isoleucine in serum. Lower concentration of taurine choline, Fbeta:RCH2CH2CO, Epi-coprostanol and lactate were found in both in thoracic gland extracts and spleen extracts. And in spleen extracts, we also found the lower concentration of 3-HB. In the extracts of bone marrow, the lower concentration of lactate, choline, glucosee were observed. When they were dosed with Siwutang 10 g x kg(-1) x d(-1) for 7 days, the effects above-mentioned were reversed.</p><p><b>CONCLUSION</b>The injury established by injecting CTX is a kind of proper model to develop further metabonomics researches. The damage of mitochondria, disorder of energy metabolism and osmoregulation are observed in cyclophosphamide caused blood deficiency model by NMR-based-metabonomics method, and the Siwutang can improve these effects.</p>

Analysis of metabonomic changes of hepatic vein plasma after oral administration of quercetin in rats / 肠外与肠内营养

Objective: To investigate the effects of quercetin on hepatic vein metabolic profiles in rats. Methods: Male Wistar rats were administrated orally with 40 mg/kg quercetin. Hepatic vein plasma was collected at 0 h, 0.5 h, 1 h, 2 h and 4 h respectively after administration and analyzed by 1H NMR. Results: The identifiable biochemical effects associated with quercetin dosing included decreased plasma concentration of glucose and increased plasma concentration of succinate,β-hydroxybutyrate and pyruvate. Conclusion: Quercetin changes hepatic metabolism in rats, manifested mainly as increased glucose catabolism and production of ketone bodies.

Comparative study on metabonomics and on liver and kidney toxicity of Aristolochia fangchi and Stephania tetrandra / 中国中药杂志

<p><b>OBJECTIVE</b>Combined the blood biochemical markers, the renal histopathological changes and the metabonomics profile were investigated to study the toxicity differences between Aristolochia fangchi and Stephania tetrandra.</p><p><b>METHOD</b>Ten rats were randomly selected from 70 male Wistar rats as blank control group. The remaining 60 rats were divided into three groups. The two treated groups were orally administrated by 8.1 g x kg(-1) of A. fangchi and S. tetrandra respectively and the control group by equal volume of distilled water for 4weeks. Before the administrated and every 2 weeks, urine and plasma were collected and their 1H-NMR spectra were acquired, and then subjected to data process and PCA. Blood biochemical analysis and histopathological examination were carried out.</p><p><b>RESULT</b>On the 2nd weekend, the BUN of the two treated groups, the AST of A. fangchi group were all markedly higher than that of the control group (P < 0.05). Compared with the A. fangchi group, the SCr higher in the S. tetrandra group (P < 0.05). The kidney pathological changes were apparently in the two treated groups and the pathological changes in the liver apparently in the S. tetrandra group. Along with the lasting of administration to the 4th week, the BUN, ALT and AST of the two treated groups, the SCr of A. fangchi group were all significantly higher than that of the control group (P < 0.01). The renal and liver injuries in the two treated groups were all become more seriously. Comparing the A. fangchi group, the BUN, SCr and AST were all higher in the S. tetrandra group (P < 0.05). Compared with control group, the urinary concentrations of citrate, 2-oxo-glutarate, taurine, hippurate, TMAO, creatine and the plasma concentrations of 3-D-hydroxybutyrate, acetone, NAC, OAC, creatinine were all changed.</p><p><b>CONCLUSION</b>The A. fangchi and S. tetrandra all can induce the renal and liver lesion and its seriousness is correspondent to the lasting of administration. The liver and kidney toxicity of S. tetrandra are all more serious than the A. fangchi.</p>

NMR-spectroscopy-based metabonomic study on mouse model of blood deficiency syndrome induced by compound method of bleeding, starved feeding and exhausting and effect of siwutang / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the essence of blood deficiency syndrome and the mechanism of the effects of siwutang based on the characteristic changes in metabolic profiles of C57 mice with blood deficiency induced by compound method of bleeding, starved feeding and exhausting before and after the treatment of Siwutang.</p><p><b>METHOD</b>Thirty C57 mice were randomly divided into three groups of 10 animals: the control group and two blood deficiency model groups without or with siwutang treatment. The animals were sacrificed after induction by compound method of bleeding,starved feeding and exhausting for 10 days and the blood, spleen, thymus and bone marrow were obtained. The metabolic profiles of serum, aqueous and lipidic extracts of thymus, spleen and bone marrow were investigated using 1H nuclear magnetic resonance spectroscopy (NMR). The NMR spectra were integrated in segments of 0.01, normalized and then analyzed using SIMCA-P software to visualize the similarities and differences in metabolic profiles between these groups.</p><p><b>RESULT</b>Compared with the control group, the model group contained different levels of lactate, choline, glucose, taurine, alanine, LDL, glycerin, UFA, creatinine, acetoacetate, glutamate and beta-hydroxybutyrate (beta-HB). In the Siwutang treated group, the above-mentioned changes were reversed.</p><p><b>CONCLUSION</b>The disorder of energy metabolism, damage of lymphocyte, and disorder of immune function were observed in blood deficiency model by NMR-based-metabonomics method, and the Siwutang can improve these effects. Metabonomics may be a valuable tool in the pharmacological evaluation of siwutang.</p>

Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics / 中西医结合学报

To study the changes of metabolites in rat urine after treatment of Aristolochia fangchi decoction by metabonomic method.

The effect of non-experimental factors on human nuclear magnetic resonance metabonomics study / 生物医学工程学杂志

Metabonomic approaches are believed to be one of the powerful methods for disease diagnosis and assessment of patients' conditions. However, many publications have been providing the evidences of the biases caused by many factors such as diet, physical exercises, environment and individual differences in the clinical researches. For the purpose of ensuring the comparability of metabonomic 1H NMR data from different studies, it is necessary to control those nonexperimental factors in the study design and the data analysis.

Establishment of rat model of syndrome of stagnation of liver qi and primary study using metabonomics / 中华中医药杂志

Objective:To establish and validate the rat model of syndrome of stagnation of liver qi,followed by a primary study on this model with 1H NMR based on metabonomics to explore the essence of syndrome of stagnation of liver qi. Methods:Twelve Wistar male rats were randomly divided into two groups(model group and control group).The rats of model group were restrained by special equipment for 21 days to get into stagnation of liver qi.The behavior,fluid consumption test and plasma CORT of rats were recorded.At 22th day,animals were sacrificed and biopsies of gastric mucosa and adrenal gland were collected for pathological check,and serum samples for 1H NMR spectroscopy.The NMR data were analyzed using principal component analysis.Results:There were abnormal behaviors,such as decrease of elusion,slackness,looser stools,and matte fur were observed among model group rats.After one week the body weight of model group was significantly lower than that of control group(P

THE METABONOMIC STUDY ON PORTAL BLOOD PLASMA OF RATS AFTER ORAL ADMINISTRATION OF QUERCETIN / 营养学报

Objective:To investigate the effects of quercetin on metabolic profiles of portal blood plasma in rats. Method:Twenty five male Wistar rats were administered orally with 40 mg/kg bw quercetin. Portal blood was collected at 0,0.5h,1 h,2 h and 4 h after dosing respectively and analyzed by 1H NMR. The acquired data were subjected to partial least-squares discriminant analysis. Results:The identified biochemical effects associated with quercetin dosing included increased plasma concentrations of dimethyl sulfoxide,lactate,glucose,alanine,glutamate,succinate,?-hydroxybutyrate,acetone and decreased plasma concentrations of citrate and tyrosine. Conclusion:Quercetin may change the intestinal endogenous metabolism significantly in rats.

Metabonomics study on nephrotoxicity of Aristolochia manshuriensis / 中草药

Objective To study the metabolic profiles in the urine samples of rats dosed with decoction of the caulis of Aristolochia manshuriensis and the relationship between the results of blood biochemical analysis and histopathological analysis,and to explore the feasibility of the application of NMR-based metabonomics to toxicology of Chinese medicine.Methods Male Wistar rats were administrated by ig 36,32,28,and 24 g/kg of A.manshuriensis or the equal volume of distilled water for 6 d,respectively.Urine were collected and their()~1H-NMR spectra were acquired,and then subjected to data process and principal component ana-(lysis)(PCA).Blood biochemical analysis and histopathological examination were carried out.Results(Compared) to control groups,the urinary concentrations of TMAO,taurine,creatinine,DMG,citrate,and DMA in dosed groups decreased,while those of acetate,alanine,and some other amino acids increased to a great extent.The dosed groups can be readily discriminated from the controls based on PCA,with acetate and TMAO as main discriminators.A good agreement was achieved within clinical chemistry,microscopically examination and PCA data.Conclusion The caulis of A.manshuriensis can induce renal lesion as revealed by the metabonomic analysis of rat urine samples as well as blood biochemical analysis and histopathological examinations.The results show that the metabonomic approach is a promising new technology in toxicology.