代谢组学与中医药现代研究

从代谢组学的技术特征出发,分析了代谢组学在中医证候模型复制、方药作用机制及中药安全性评价等领域应用的价值及可能性,认为代谢组学将成为中医药现代研究的重要技术方法。

Pharmacokinetics of Recombinant E. coli L-asparaginase in Rats

The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted in urine, feces and bile within 24 h afterintravenous administration of ^(125)I recombinant E. col L-asparaginase to rats was 68.95% ,4.44%and 5.36% of the dose respectively. ^(125)I recombinant E. coli L-asparaginase in plasma samples wasdetermined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGEand bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model-dependentmethod. The concentration-time curves of recombinant E. coli L-asparaginase after intravenousinjection at 1 250 IU·kg^(-1), 2 500, IU·kg^(-1), 5 000 IU·kg^(-1) to rats were consistent withthe two-compartment model. The first and terminal elimination t_(1/2) were 0.52 ~ 0.63 h and 2.39 ~2.76 h respectively. AUC was linearly related to the doses. The results of distribution in tissuesor organs and excretion in urine suggested that the metabolites of the enzyme were cleared bymechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E. coli L- asparaginasein rats are warranted for the design of future clinical trials.

Overview on metabolomics in traditional Chinese medicine

Metabolomics has been widely used in the modern research of traditional Chinese medicine （TCM）. At the same time, the world is increasingly concerned about TCM, and many studies have been conducted to investigate different aspects of TCM. Among these studies, metabolomic approach has been implemented to facilitate TCM development. The current methods for TCM research are diverse, including nuclear magnetic resonance, gas chromatography-mass spectrometry, and liquid chromatographymass spectrometry. Using these techniques, some advantageous results have been obtained in the studies of TCM, such as diagnosis and treatment, quality control, and mechanisms of action. It is believed that the further development of metabo-lomic analytical techniques is benefcial to the modernization of TCM. This review summarizes potential applications of metabolomics in the area of TCM. Guidelines for good practice for the application of metabolomics in TCM research are also proposed, and the special role of metabolomics in TCM is highlighted.

1~H NMR-based serum metabolic profiling in compensatedand decompensated cirrhosis

AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A 1H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R2Y of 0.784 and a Q2Y of 0.598. Twelve metabolites, such as pyruvate, phenylala-nine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: 1H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.

Baoyuan decoction alleviates myocardial infarction through the regulation of metabolic dysfunction and the mitochondria-dependent caspase-9/3 pathway

Objective:Baoyuan decoction(BYD)is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests.The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction(MI).Methods:Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation.Oxygen-glucose deprivation/recovery(OGD/R)model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD.Results:BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI.Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway.Conclusions:Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways.They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.

Protective effects of Fufang Ejiao Jiang against aplastic anemia assessed by network pharmacology and metabolomics strategy

Objective To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang(复方阿胶浆,FFEJJ)on aplastic anemia(AA)using integrated network pharmacology and serum metabolomics.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP),Pubmed,integrative pharmacology-based research platform of traditional Chinese medicine(TCMIP),and Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine(BATMAN-TCM)were used to identify the constituents and putative targets of FFEJJ.Gene Cards and DisGeNET databases were used to identify AA-associated targets.We constructed a herb-component-target network and analyzed the protein-protein interaction(PPI)network.Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In addition,an AA model was established using acetylphenylhydrazine(APH)and cetylphenylhydrazine(CTX).Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)-based serum metabolomics was applied to screen potential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ.Results A total of 30 active components of FFEJJ and 24 targets were related to AA.PPI network analysis showed that VEGFA,AKT1,IL-6,CASP3,and ICAM1 were key nodes overlapping with proteins known to be related to AA.KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hematopoiesis and improvement of the hematopoietic microenvironment.A total of 423 metabolite biomarkers were identified between the control and AA models,which are involved in the development of AA.In contrast,FFEJJ reversed the 79 differential metabolites altered by AA.Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways.Among them,sphingolipid metabolism,glycerophospholipid metabolism,and arachidonic acid metabolism were related to promoting hematopoiesis and improving the hematopoietic microenvironment,which partially conforms with network pharmacology.The interaction network formed by three key differential metabolites,including hydroxy-eicosatetraenoic acid(HETE),sphingosine 1-phosphate(S1 P),and lysophosphatidylcholine(lyso PC),and three predicted network targets(VEGFA,CASP3,and ICAM1)may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ.Conclusion FFEJJ could be an alternative treatment option for AA.It acts by promoting hematopoiesis and improving the hematopoietic microenvironment.Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.

Effects of Fuke Qianjin Formula on hormones and their receptors and metabonomics study in uterine fibroids model rats

Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysaccharides(FKP),flavonoids(FKF),and grease(FKG).140 female SPF SD rats were divided into 14 groups[model(MOD),normal control(NC),Gouliuqing(GLQ),Mifepristone(MFST),FKQJF,low,medium,and high dose of polysaccharides(l-FKP,m-FKP,and h-FKP),low,medium,and high dose of flavonoids(l-FKF,m-FKF,and h-FKF),low,medium,and high dose of grease(l-FKG,m-FKG,and h-FKG)],and uterine fibroids model rats were treated with drugs for four weeks.Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay(ELISA)kits.The expression of estrogen receptor(ER-α,ER-β)and progesterone receptor(PR)in the uterus was observed using immunohistochemistry(IHC).Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry(GC-MS).Results FKQJF,h-FKF,m-FKG,and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats(P<0.01).FKQJF,h-FKF,and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats(P<0.01).The levels of ER-α,ER-β,and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG(P<0.01).The levels of ER-α,ER-β,and PR in the fibroid model rats were decreased by m-FKG(P<0.05).Additionally,serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group.Forty-six components were identified in the oil,accounting for 91.97%of the total oil components.Conclusion FKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma.The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals.These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.

A Metabolomics Study of the Volatile Oil from Prunella vulgaris L.on Pelvic Inflammatory Disease

Objective Pelvic inflammatory disease(PID)is one of the most common gynaecological diseases.Here,this thesis aims to investigate the therapeutic effects of Prunella vulgaris L.oil on the PID by using metabolomics based on gas chromatographymass spectrometry(GC-MS)to address this challenge.Methods First,measurements of pro-inflammatory cytokines and histological analysis of the uterus were conducted to validate the successful generation of a PID rat model.Furthermore,the volatile oil from Prunella vulgaris L.was administered to treat PID rats.Serum samples were collected before and after treatment and analyzed by GC-MS to generate metabolite profiles for each sample.The information generated from the qualitative and quantitative analysis of these metabolites was applied to distinguish between the PID model and normal control groups.Results Some metabolites,such as acetic acid,succinic acid,glyceric acid,(R*,S*)-3,4-dihydroxybutanoic acid,3-hydroxyphenylacetic acid,D-ribose and myo-inositol showed a higher contribution in the classification model;thus,they can be considered as potential biomarkers.Furthermore,the therapeutic effect of the volatile oil extracted from Prunella vulgaris L.could also be visualized using GC-MS-based metabolomics.Conclusions The results show that metabolomics studies are invaluable for disease diagnosis and therapeutic effect estimation.

Metabonomics/metabolomics analysis technology and its application in quality control of traditional Chinese medicines

Chinese medicines are an important part of traditional Chinese medicines,but their'safe,effective,stable and controllable'issue still remains to be solved.The rise of metabonomics in 20th century,consistent with the overall adjustment concept of multi-component,multi-level,multi-target,multi-metabolic pathways of traditional Chinese medicines,is conducive to solve basic problems in their quality control.This paper systematically describes recent application and development of 1H-NMR metabonomics techniques,LC-MS metabonomics techniques and GC-MS metabonomics techniques in the quality control of traditional Chinese medicines.It provides a new reference for Chinese medicines and the identification and quality assessment of their products.

Metabonomic study of rats exposed to cigarette sidestream smoke

A metabonomic approach was undertaken in order to detect urinary endogenous and exogenous metabolites and to evaluate the effects of passive exposure to cigarette sidestream smoke on rats. Urinary samples from three groups of rats were determined including control rats, rats treated with blended cigarettes(nonmenthol cigarettes) and rats treated with menthol cigarettes. The total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol(NNAL), total 1-hydroxypyrene(1-HOP) and 3-hydroxybenzo[a] pyrene(3-HOBaP) were determined for assessing exposure to cigarette sidestream smoke toxins. Urinary endogenous metabolites in the three groups of rats were also analyzed and the data were processed by chemometrics. Eleven endogenous metabolites were found and identified. Their relative levels were compared among the three groups. The results show that cigarette sidestream smoke has complex effect on rats. Blended cigarette group makes difference to menthol cigarette group in the rats' urinary metabolic changes. Menthol adding to cigarettes has positive and negative effects on rats, respectively. The urinary metabolic profiling of menthol cigarette group is closer to that of control group.

Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?

The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered.

Orlistat-lnduced Modulation of Plasma Metabolites Independent of Weight Loss in Overweight Females

Orlistat-induced weight loss results in amelioration in several comorbidities including obesity-related dyslipidemia. The aim of the present study was to characterize the changes in the blood plasma metabolic profile from overweight women treated with Orlistat, a lipase inhibitor. A metabonomic approach employing LHNMR was applied to the access metabolic profile in lean and overweight women after a 120 day treatment with 120 mg of Orlistat three times daily. Twenty overweight women （BMI： 32.8 ± 2.9 kg/m2） were evaluated before and after Orlistat treatment and seven normal weight women （BMh 21.8 ± 1.4 kg/m2） were taken as control. After 120 days of treatment with Orlistat, no significant weight changes were observed. However, Orlistat-induced metabolic changes in overweight subjects decreased the profile differences between lean and obese individuals, independent of weight loss. These were associated to decreasing levels of lactate and calcium. Higher levels of lactate, alanine and lipids from overweight subjects were detected in comparison to lean individuals. These results show that a lipase inhibitor shifts the metabolic profile of overweight subjects towards normality, independent of weight loss.

Metabolomics Study in Methylotrophic Yeast： A Minireview

Methylotrophic yeast has been used as a cost-effective and valuable host for expression of recombinant protein due to its unique methanol utilisation pathway. It has an AOX （alcohol oxidase） protein which has been characterised to be a strong and tightly methanol-inducible dependent promoter. Metabolomics is the systematic study and inclusive analysis of small molecules called metabolites in a biological system. Metabolomics plays an important part in connecting the phenotype and genotype gap because it magnifies the modifications in the proteome and provides a better phenotype representation of an organism. This quantitative study has provided a new perception on the metabolic burden derived from the overexpression of recombinant protein in methylotrophic yeast. In this review, we discuss the fundamental aspect of metabolomics in methylotrophic yeast followed by their latest developments.

Effects of Gancao Nourish-Yin Decoction on Liver Metabolic Profiles in hTNF-αTransgenic Arthritic Model Mice

Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.

Non-alcoholic steatohepatitis with normal aminotransferase values

AIM： To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis （NASH） who had normal aminotransferase levels. METHODS： Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non- alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio and presence of metabolic syndrome. RESULTS： Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. CONCLUSION： Aminotransferase levels and AST/AIT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.

Holistic quality evaluation of Panax notoginseng extract and injection using an UPLC-QTOF-MS^E based metabolomics approach

In the present study, we established an UPLC-QTOF-MSE based metabolomic approach in order to evaluate the holistic qualities and compare the quality difference by finding characteristic components of Panax notoginseng extracts （PNE） and Xuesaitong （XST） injection samples from different manufacturers. The data were processed through unsupervised principal component analysis （PCA） and supervised orthogonal partial least squared discrimination analysis （OPLS-DA） to compare the quality differences. Two-dimensional PCA score plots showed a tendency to separate the XST injections and extracts, and most XST injection samples were clearly clustered into two groups. Especially, the injections from He and YB companies were distinguished into two groups. In addition, only injection samples of Hu company were near the cluster of PNE. To explore the potential chemical components contributing most to the differences between XST injection samples from different manufacturers and PNE, an S-plot was constructed following the OPLS-DA. Ginsenoside Rd, ginsenoside Rgl, ginsenoside Re, ginsenoside Rbl, 20（S）-ginsenoside Rhl, gypenoside VII, ginsenoside Rg2, ginsenoside Rh4, ginsenoside Rkl or Rgs, notoginsenoside Fc, 20（R）-ginsenoside Rg3, ginsenoside F2 and protopanaxadiol were recognized as characteristic chemical markers that contributed most to reflect the difference between XST injections and PNE. Ginsenoside Rd, ginsenoside Rgl, ginsenoside Re, ginsenoside Rbl and gypenoside VII were revealed as index components contributing most to the differences of PNE and XST injections, and quantitative analysis of these components could ensure the consistent quality of XST injections. Based on the fact that the injections should be standardized with the characteristic components as quality control chemical markers, it is most important to keep the quality of extracts of raw materials stable and reliable.

Recent advance in SNP identifying methods and individualized medication

Polymorphisms associated with genes coding for a variety of drug-metabolizing enzymes （DMEs） and associated transport proteins can influence the drug metabolism rate of individuals, potentially affecting the efficacy of drug and the occurrence of adverse reactions. Single nucleotide polymorphisms （SNPs） are prevalent in all types of genetic variations. Reliable SNP genotyping provides excellent markers for detecting genetic polymolphisms, genetic disorders, and resistance of pathogen to drug, which are needed for the genetic diagnosis of disease and subtle genetic factors. With a large number of SNP genotyping studies being conducted, a lot of novel SNP identifying methods have been developed. Several SNP genotyping methods and techniques have been introduced for clinical test. These include TaqMan drug metabolism genotyping assays, pH-sensing semiconductor system, high-resolution melting curve analysis （HRM） of polymerase chain reaction （PCR） amplicons, novel multiplexed electrochemical biosensor with non-fouling surface, DNA hybridization detection using less than 10-nm gap silicon nanogap structure, tetra-primer ARMS-PCR method, acoustic detection of DNA conformation in genetic assays combined with PCR, microbeads-mass spectrometry （MEMS）-based approach, and liquid chromatography-electrospray ionization mass spectrometry. Personalized medicine has changed the conventional ways of using drugs according to experiences. It focuses on making the individualized pattern for each individual based on their own characteristics. Lots of researchers are using the analysis of clinical samples to explain the relationship between the drug adverse reactions and genetic polymorphisms. But it takes a long time from collecting the blood samples for DNA extraction and genotyping to getting results on the side effect of drug through clinical study. Therefore, it is desirable to develop improved in vitro methods to study the drug metabolizing-enzymes and transport protein genetic polymorphisms.

Urine metabonomic study for blood-replenishing mechanism of Angelica sinensis in a blood-deficient mouse model

This study aimed at determining the effects of Angelica sinensis(AS) on urinary metabolites in blood deficiency mice and exploring its replenishing blood mechanism. Gas chromatography–mass spectrometry(GC-MS) was applied to detect metabolites in the urine samples in different collection periods. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to investigate the differences in metabolic profiles among control group(CG), blood deficiency model group(MG), AS groups, and Colla Corii Asini group(CCAG). The potential biomarkers were identified based on the variable importance in the projection(VIP), T-test, and National Institute of Standards and Technology(NIST) and mass spectra library. The metabolites were analyzed using metabolomics pathway analysis(Met PA) to build the metabolic pathways. Our results indicated that, on the seventh day, the levels of glucose, lactic acid, pyruvic acid, alanine, acetoacetic acid, and citric acid changed significantly in blood deficiency mice. However, these metabolic deviations came to closer to normal levels after AS intervention. The reversing blood-deficiency mechanism of AS might involve regulating synthesis and degradation of ketone bodies, Pyruvate metabolism, TCA cycle, and Glycolysis / Gluconeogenesis. In conclusion, metabonomics is a robust and promising means for the identification of biomarkers and elucidation of the mechanisms of a disease, thereby highlighting its importance in drug discovery.

Tissue lipid metabolism and hepatic metabolomic profiling in response to supplementation of fermented cottonseed meal in the diets of broiler chickens

This study investigated the effects of fermented cottonseed meal（FCSM） on lipid metabolites, lipid metabolism-related gene expression in liver tissues and abdominal adipose tissues, and hepatic metabolomic profiling in broiler chickens. One hundred and eighty 21-d-old broiler chickens were randomly divided into three diet groups with six replicates of 10 birds in each group. The three diets consisted of a control diet supplemented with unfermented cottonseed meal, an experimental diet of cottonseed meal fermented by Candida tropicalis, and a second experimental diet of cottonseed meal fermented by C. tropicalis plus Saccharomyces cerevisae. The results showed that FCSM intake significantly decreased the levels of abdominal fat and hepatic triglycerides（P〈0.05 for both）. Dietary FCSM supplementation down-regulated the m RNA expression of fatty acid synthase and acetyl Co A carboxylase in liver tissues and the lipoprotein lipase expression in abdominal fat tissues（P〈0.05 for both）. FCSM intake resulted in significant metabolic changes of multiple pathways in the liver involving the tricarboxylic acid cycle, synthesis of fatty acids, and the metabolism of glycerolipid and amino acids. These findings indicated that FCSM regulated lipid metabolism by increasing or decreasing the expression of the lipid-related gene and by altering multiple endogenous metabolites. Lipid metabolism regulation is a complex process, this discovery provided new essential information about the effects of FCSM diets in broiler chickens and demonstrated the great potential of nutrimetabolomics in researching complex nutrients added to animal diets.

~1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension

OBJECTIVE; To observe the influence of Qingrehuatan decoction （QRHT） on serum metabolic profile in young essential hypertension （YEH） patients with abundant phlegm-heat syndrome and provide a basis for treatment with the decoction. METHODS： Twelve male YEH patients were randomly selected and serum samples were collected for examination before and after 4 weeks of thetreatment with QRHT. Twelve healthy males were randomly selected and their serum samples were collected as a control. All serum samples were detected using metabolomic technology with 1H nuclear magnetic resonance. Differences in metabo- lites were studied by principal component analysis and partial least squares-discriminate analysis, which produced scores and Ioadings plots.RESULTS： After 4 weeks of treatment, serum substances could be distinguished between the YEH patients with abundant phlegm-heat syndrome and the control patients. The specific serum endogenous metabolites tended to improve after the treatment. QRHT can appropriately increase the levels of glucose, lactic acid, citric acid, high-density lipoprotein, phosphatidylcholine, glycerophosphate choline, hydroxybutyrate, alanine, and glutamate. QRHT could also decrease the levels of low-density lipoprotein/very low-density lipoprotein, lipids, N-acetyl glycoprotein, and O-acetyl glycoprotein.CONCLUSION： QRHT can effectively ameliorate metabolic disorders in YEH Patients with abundant phlegmheat syndrome. 1H NMR-based metabolo- mic technology can provide an objective basis for the treatment of YEH patients with abundant phlegm-heat syndrome using QRHT.