Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Heat stroke alters hippocampal and cerebellar transmitter metabonomics

BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.

A new metabonomics method for simultaneous determination of EFAs and NEFAs in plasma using GC-MS and its application

A new metabonomics method was developed for simultaneous qualitative and quantitative analysis on esterified and nonesterified fatty acids （EFAs and NEFAs） in plasma. Merely 10 μL of plasma was required. The pretreatment of the sample was simple without disposing the protein. After simple extraction and derivation, 15 FAs in plasma were precisely quantified. Gas chromatography tandem mass spectrometry （GC-MS） was used in the study and the quantities of the analytes, which varied in abundance over three orders of magnitude. The established method showed good accuracy. The curve correlation coefficients were all above 0.997. The RSDs of precision for all compounds were below 15% and recoveries were all between 80 and 110%. PLS-DA modal was used in the data management. 2009 Guo An Luo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Application of the Reversed-phase Liquid Chromatography Coupled to Ion Trap Mass Spectrometry with Principal Components Analysis for Metabonomics Studies of Scutellarin in Rat Urine

Metabonomics, a novel systemic approach, was applied to studies of Traditional Chinese Medicine scutellarin in rat urine. The liquid chromatography coupled with ion trap mass spectrometry combined with PCA was used in this paper. With this methodology, two potential metabolites of scutellarin were detected and the nine ions responsible for the gender variation and one ion for the dosage variation were found.

Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin （300 ng/kg chow） for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lyso PE （18：0/0：0）, lyso PC（14：0）, lyso PC[18：4 （6Z,9Z,12Z,15Z）], lyso PC[（16：1（9Z）], lyso PC（16：0）, L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways.

UPLC-Q/TOF-MS based metabonomics revealed protective effect of Terminalia chebula extract on ischemic stroke rats

Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not unclear.The present study focused on the effects of TC on metabonomics in stroke model.In our study,rats were divided randomly into Sham,Model,and TC groups.The TC group were intragastricly administered with TC for 7 d after middle cerebral artery occlusion(MCAO)operation.The sham and the model groups received vehicle for the same length of time.Subsequently,the neuroprotective effects of TC were examined by neurological defects evalua⁃tion,infarct volume assessment,and identification of biochemical indicators for antioxidant and anti-inflammatory activi⁃ties.Further,metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically.Consist to results of biochemical and histopathological assays,pattern recognition analysis showed a clear separation of the Model and the Sham group,indicating a recovery impact of TC on the MCAO rats.Moreover,12 potential biomarkers were identified in MCAO Model group,involved in energy(lactic acid,succinic acid,and fumarate),amino acids(leucine,alanine,and phenylalanine)and glycerophospholipid[PC(16∶0/20∶4),PC(20:4/20:4),LysoPC(18:0)and LysoPC(16:0)]metabolism,and other types of metabolism(arachidonic acid and palmitoylcarnitine).Notably,we found that metabolite levels of TC group were partially reversed to normal.In conclusion,TC could ameliorate MCAO rats by intervening with energy metabolism(glycolysis and TCA cycle),amino acid metabolism,glycerophospholipid metabolism and other types of metabolism.

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.

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Microbial phenolic metabolites 3-(3',4'-dihydroxyphenyl)propanoic acid and 3',4'-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.

Metabolite acetyl-L-carnitine participates in Bifidobacterium animalis F1-7 to ameliorate atherosclerotic inflammation by downregulating theTLR4/NF-κB pathway

This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.

Study of Serum Metabonomics and Formula-Pattern Correspondence in Coronary Heart Disease Patients Diagnosed as Phlegm or Blood Stasis Pattern Based on Ultra Performance Liquid Chromatography Mass Spectrometry

Objectives： To study the characteristics of serum metabonomics in coronary heart disease （CHD） patients diagnosed as phlegm or blood stasis pattern and explore effects of formula-pattern correspondence treatment. Methods： A total of 102 stable CHD patients were enrolled and divided into phlegm group （P group, n=52） and blood stasis group （BS group, n=50） according to pattern identification. Gualou Xiebai Banxia Decoction （瓜萎薤白半夏汤, GXBD） and Xuefu Zhuyu Decoction （血府逐瘀汤, XZD） were used as drug interventions. Relevant indicators of metabonomics were observed by ultra performance liquid chromatography mass spectrometry （UPLC-MS） and pattern recognition. Results： Levels of amino acids and phosphatidylethanolamine （PE） in the CHD group were much higher than those in healthy control group, while the levels of unsaturated fatty acids, sphingosine, Lyso, phosphatidylcholine （PC） were significantly lower （P〈0.01）. Most of the differential metabolites between the CHD and the healthy groups were also common metabolites of phlegm and blood stasis. 7（Z）, 10（Z）- hexadecadienoic acid and DPA were decreased in the P group and increased in the BS group. According to the quantity of retraced metabolites, improvement in metabonomics by formula-pattern correspondence was superior to that without correspondence in the BS group. Based on the varieties of metabolites, GXBD could improve the levels of docosapentaenoic acid （DPA）, sphingomyelin （SM） （d34：1）, and L-Lactic acid and XZD could ameliorate the levels of sphingosine and Vit E in the P group, in the BS group, GXBD could improve vitamin E level and XZD could make improvements in the levels of octadecanoic acid, phosphoglycerol, and SM （d34：1）. Conclusions： Phlegm and blood stasis in CHD patients present specific differential metabolites, and share common metabolites. Remarkable differences have been displayed in pathological properties and severity of phlegm and blood stasis. Patients with phlegm are more likely to have lipid metabolism disorders. However, in patients with blood stasis, problems mainly lie in glucose, protein and fat metabolism and the injury of vascular cell membrane is relatively severe. The metabolic disorder is more complicated in blood stasis pattem than that in phlegm pattem. Compared with non-correspondence, improvement of differential metabolites is more comprehensive and targeted in formulapattern correspondence with a better effect.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry

Shuang-huang-lian Injection(SHLI) is the first successfully developed drug from traditional Chinese medicine(TCM) powder for injection,since its use for the treatment of acute respiratory tract infection,pneumonia,influenza,etc.At the same time,its allergic reactions have also emerged,which limits clinical applications.However,few scholars pay attention to the mechanism of allergic reactions.In this present study,metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction;we and analyzed the metabolites,metabolic pathway,and the mechanism which were closely related to the allergic reactions.The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed.Based on the UPLC-Q-TOF/MS metabonomics,we carried out the pattern recognition analysis,selected potential biomarkers associated with allergic reactions,and explored the pathological mechanism for SHLI induced allergic reaction,which laid the foundation for the safety research of SHLI.Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction;we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved,such as metabolism of linolenic acid,phenylalanine,amino acid,2-oxo acid,and purine and other metabolic pathways.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

Metabonomics:A Useful Tool to Reveal Underlying Relationships between Altered Chinese Medicine Syndromes and Ultrafiltration in Treatment of Heart Failure

Objective:To reveal the underlying relationships between Chinese medicine(CM)syndromes and ultrafiltration(UF)in the treatment of heart failure based on a metabonomic approach.Methods:Seventeen acute decompensated heart failure(ADHF)patients were enrolled,and their CM syndromes before and after UF were collected.In addition,their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis.Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples.Partial least-squares to latent structure-discriminant analyses were used for data analysis.Results:An obvious difference was observed preand post-treatment.A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine,1-methylhistidine,phytosphingosine,O-decanoyl-R-carnitine,etc.were screened out,showing a significant change after UF.The major adjusted m etabolic pathways were purine metabolism,histidine metabolism,leucine and isoleucine metabolism,arginine and proline metabolism,carnitine shuttle,sphingolipid metabolism and phospholipid metabolism.Conclusions:Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

Design and baseline data of a populationbased metabonomics study of eye diseases in eastern China: the Yueqing Ocular Diseases Investigation

Background:China is undergoing a massive transition toward an urban and industrial economy.These changes will restructure the demographics and economy which will eventually influence the future patterns of disease.The risk factors of vision-impairing eye diseases remain ambiguous and poorly understood.Metabolomics is an ideal tool to understand and shed light on the ocular disease mechanisms for earlier treatment.This article aims to describe the design,methodology and baseline data of the Yueqing Ocular Diseases Investigation(YODI),a developed county population-based study to determine the prevalence and primary causes of visual impairment;also with metabonomics analysis we aimed to identify,predict and suggest some preventive biomarkers that cause blindness.Methods:A population-based,cross-sectional study.Randomized clustering sampling was used to identify adults aged 50 years and older in Xiangyang Town,Yueqing county-level City.The interviews covered demographic,behavioral,ocular risk factors and mental health state.The ocular examination included visual acuity,autorefraction,intraocular pressure,anterior and posterior segment examinations,fundus photography,retinal tomography and angiography,and visual field testing.Anthropometric measurements included height and weight,waist and hip circumference,blood pressure,pulse rate,electrocardiogram,and abdominal ultrasound scan.A venous blood sample was collected for laboratory tests and metabonomics studies.Results:Of the 5319 individuals recruited for the YODI,4769(89.7%)subjects were enrolled for analyses.The median age was 62.0 years,and 45.6%were male.The educational level of illiteracy or semi-illiteracy,primary,middle and high school or above was 29.8%,45.5%,20.1%,and 3.3%,respectively.Majority of the participants were female,younger,and less educated when compared with nonparticipants.The average body mass index and waist-hip ratios were 24.4±3.4 kg/m^(2) and 0.9±0.1 respectively.Blood sample collection reached a sample size of 1909(479 from subjects with selfreported diabetes and 1430 from one-third of the 4290 subjects without self-reported diabetes).Conclusions:The YODI provides population-based data with a high response rate(89.7%)on the prevalence and primary causes of major vision-impairing eye diseases in developed county areas in eastern China.Metabonomics analysis from YODI will provide further association of metabolic characteristics with the visual impairment eye diseases.The risk prediction model could be created and has the potential to be generalized to developed eastern areas in China for prevention.

Liver metabonomics study on the protective effect of glycyrrhetinic acid against realgar-induced liver injury

Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et Rhizoma.Our previous study has reported that GA has protective effect on realgar-induced hepatotoxicity.However,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be elucidated.In the study,mice were divided into control,GA-control,realgar,and co-treated groups.Their liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)method.The results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by realgar.Some metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of GA.These metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative stress.From the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.

Urinary metabonomics of stomach cancer assessed by rapid resolution liquid chromatography/time-of-flight mass spectrometry

Background Stomach cancer is among the most commonly occurring malignancies worldwide. It would be beneficial to develop a urine-based assay whereby patients with undiagnosed stomach cancer could be screened and their cancer detected in the eadiest stages. Methods A urinary metabonomics method based on ultra-performance liquid chromatography combined with quadruple time-of-flight mass spectrometry was used to analyze urine samples from patients with stomach cancer and healthy controls. Results Statistical analysis revealed a clear separation of patients and healthy controls using the aforementioned methodology. Some significantly changed metabolites were identified. Conclusions Use of the metabonomics method in patients with stomach cancer could effectively detect distinct changes in urinary metabolites and had the capacity to detect cancer; therefore, it may be a valuable tool in earlier diagnosis. Furthermore, the detection and identification of altered metabolites in the current study may help elucidate possible mechanisms involved in stomach cancer.

Influence of Chromatogram Baseline Shifts and Exogenous Metabolite Signals on Metabolic Profiles of Traditional Chinese Medicine Chaihu and Its Liver Toxicity Metabonomics

In an LC-MS investigation of drug metabolic samples from the traditional Chinese medicine Chaihu, the baseline was established via MS selectivity-based chromatogram baseline-shift elimination and exogenous metabolite signals were obtained with MS-based orthogonal projection. Their respective influences on the metabolic chromato- graphic profiles, metabonomics model and evaluation of drug toxicity were investigated. The baseline shift enhanced the difference between the metabolic profiles of the control and Chaihu groups, and the corresponding correlation coefficient decreased from 70.38% to 62.69%. The exogenous metabolite signal led to a biased expression of the evaluated toxicity, and the enhanced expression resulted in an average Mahalanobis distance of approximately 9.4%. Based on established metabonomics models, the results show that Chaihu induces liver toxicity at a lower dose of 25 g/kg, twice a day. At this dose, Chaihu elicits a process of self-repair for its liver toxicity. The signal intensities of exogenous metabolites from Chaihu changed with the administration time, but only the signal intensities of large molecule metabolites（m/z 500--850） from Chaihu had a positive correlation with its toxicity. These results suggest that liver toxicity from low doses of Chaihu was probably caused by the larger molecule components and not by its active components, saikosaponin and flavonoid glycoside.

Analgesic Activity of Jin Ling Zi Powder and Its Single Herbs:A Serum Metabonomics Study

Objective:To compare the analgesic effect of Jin Ling Zi Powder(JLZ)and its two single herbs.Methods:The hot plate method was used to induce pain.Totally 36 mice were randomly divided into 6 groups by a complete random design,including control,model,aspirin(ASP,0.14 g/kg body weight),JLZ(14 g/kg body weight),Corydalis yanhusuo(YHS,14 g/kg body weight),and Toosendan Fructus(TF,14 g/kg body weight)groups,6 mice in each group.The mice in the control and model groups were given the same volume of saline,daily for 2 consecutive weeks.At 30,60,90,and 120 min after the last administration,the pain threshold of mice in each group was measured,and the improvement rate of pain threshold was calculated.Serum endogenous metabolites were analyzed by gas chromatography–mass spectrometry(GC–MS).Results:There was no statistical difference in pain threshold among groups before administration(P>0.05).After 2 weeks of administration,compared with the model group,the pain threshold in JLZ,YHS,TF and ASP groups were increased to varying degrees(P<0.05).JLZ had the best analgesic effect and was superior to YHS and TF groups.A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs.These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism,glycine,serine and threonine metabolism,valine,leucine and isoleucine biosynthesis,aminoacyl-t RNA biosynthesis and inositol phosphate metabolism.Conclusions:The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor,producing post-synaptic potential,reducing the excitability of neurons,and weakening the afferent effect of painful information.

Metabonomics study of liver and kidney subacute toxicity induced by garidi-5 in rats

Objective:Metabonomics was used to analyze and explore the biomarkers and possible mechanisms of liver and kidney subacute toxicity induced by garidi-5 in rats.Methods:Taking garidi-5 as the target drug and SD rats as the research objects,each administration group except the normal group was intragastric administration of the corresponding drug solution for28 d.The serum,liver and kidney samples of rats were detected by metabolomics and characterized by principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)to identify the sensitive markers and metabolic pathways of liver and kidney subacute toxicity.Results:Metabolomics analysis showed that compared with the normal group(Z),the 52,64 and 54 different metabolites were identified in the serum,liver and kidney samples of garidi-5 high dose group(GG),which were mainly enriched in ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism,central carbon metabolism in cancer pathways.Conclusion:The preliminarily suggested that garidi-5 can damage the liver and kidney by affecting the ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism pathways,etc.Trimethylamine N-oxide,L-pyroglutamic acid,glycine-betaine,xanthine,glutathione,L-leucine,cytidine,L-arginine,spermidine,urea,5-aminovaleric acid,creatine,L-glutamic acid,1-methylnicotinamide and S-adenosyl-L-methionine can be used as potential biomarkers of liver and kidney toxicity sensitivity.