Analysis of Intervention of Erxiantang in Ovariectomized Rats by LC-MS Serum Metabolomics / 中国实验方剂学杂志

ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Exploration on molecular mechanism of hot herb Aconitum carmichaelii for therapeutic action based on metabolomics / 中草药

Objective: To observe the effects of Aconitum carmichaelii on serum metabolites in mice by metabolomics technology, and to explore biomarkers and metabolic pathways and targets related to its treatment of various ailments such as cardiovascular diseases, in order to uncover its molecular mechanism of efficacy. Methods: Twenty male mice were randomly divided into two groups, and A. carmichaelii decoction and distilled water were orally administered with the dose of 15 mL/(kg∙d) for consecutive 4 d respectively. Collected blood samples of each group were analyzed using UPLC-MS/MS technology, and data pattern recognition was performed using PCA, PLS-DA and other analytical methods. Meanwhile, differential metabolites were screened out based on VIP greater than 1 and manual integral calculation. The differential metabolites were used for pathway analysis. Network modular analysis and targets screening were performed by Cytoscape and MetScape. Results: When performing data pattern recognition, the aconite group and the control group could be completely separated. A total of 18 differential metabolites were screened out, and their contents were up-regulated. Pathway analysis was performed to obtain five related pathways, namely linoleic acid metabolism, arachidonic acid metabolism, starch and sucrose metabolism, nicotinate and nicotinamide metabolism, and inositol phosphate metabolism. Fourteen modules were obtained using the network analysis, the largest two of which were arachidonic acid metabolism pathway and linoleic acid metabolism pathway. The degree of arachidonic acid (59), linoleic acid (55), nicotinamide (26), and palmitic acid (11) were greater than the mean value (8.010) in the network, and the related pathways were arachidonic acid metabolism, linoleic acid metabolism, nicotinate and nicotinamide metabolism, and saturated fatty acid beta-oxidation pathway respectively. A total of 26 genes were screened out, all of which belonged to the cytochrome P450 enzyme system. Conclusion: A. carmichaelii may affect arachidonic acid metabolism by acting on CYP450, thereby improving the body's energy metabolism and producing therapeutic effects.

Metabolomic investigate into the serum of pulmonary hypertension Beagle dogs and the effect of sGC003 / 药学学报

Based on dehydrogenation of monocrotaline-induced Beagle dog model of pulmonary hypertension (PH), GC-TOF-MS metabolomics technique was used to identify potential biomarkers and biologically significant changes in the serum. Pattern recognition method was used for processing metabolomics data to compare PH Beagle dogs (n=11) versus healthy controls (n=8). The results show that 514 compounds were detected in the serum. The profiles of PH models and healthy controls can be distinguished clearly, indicating that there are significant differences in the metabolic profiles. Data analysis revealed 15 types of potential biomarkers, including amino acids glycine and 3-cyanoalanine, glucose, fructose, 1-monopalmitic acid glycerin, and malic acid. Diversified metabolites and their metabolic pathways have been analyzed. We found that different degrees of turbulence and disorganization occurred in glyoxylate and dicarboxylate metabolism, TCA cycle, starch and sucrose metabolism pathways in the Beagle dogs. A soluble guanylate cyclase activator, 4,6-diamino-2-[1-(3-fluorothiophen-2-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl-N-methyl methyl carbamate (sGC003), was administered (n=15) for comparison with the model and the control. We found that three groups were clearly clustered, indicating that there were differences in the three groups of metabolites. ANOVA statistical analysis results suggested that sGC003 exhibited pharmacodynamic effect, and at the same time, it also changed the endogenous metabolites to some extent. This study laid a foundation for the application of metabolomics in early diagnosis of pulmonary hypertension and provided experimental evidence for the application of sGC003 compound. In this study, the program of animal testing had been approved by Committee on the management of experimental animal in the Beijing Rixin Technology Co. Ltd.

Effect of Different Antisepsis Measures on Endogenous Metabolites in Rat Urine / 中国实验方剂学杂志

Objective:In the study of urine metabolomics of rats,necessary antiseptic measures should be taken for collection of urine samples,the effect of several antiseptic measures on the endogenous metabolites in urine was studied. Method:The urine samples of rats were collected on ice,sodium azide was added,and both of them were used together to prevent corrosion.Differences of antiseptic measures were analyzed by nuclear magnetic resonance (NMR) metabolomics. Result:The results of NMR metabolomics showed that sodium azide+ice group and ice group had many overlaps,but they clearly separated with the control group and sodium azide group;sodium azide group and the control group had a small part overlap,but there was a tendency of separation.The antiseptic effect of sodium azide+ice group and ice group was similar;compared with control group,valine,betaine and hippuricacid in these two groups increased,but the alanine and 2-ketoglutaric acid decreased. Conclusion:In the study of rat urine metabolomics,low temperature antiseptic measures must be taken when urine samples are collected,and the addition of sodium azide can improve the antiseptic effect slightly under protective conditions.

1H-NMR metabolomics analysis of changes of serum metabolites in rats with depression induced by Compound Chaigui Prescription / 中草药

Objective To analyze the effect of Compound Chaigui Prescription on the changes of serum metabolites in rats with depression by 1H-NMR metabolomics. Methods Rats model established were modeled by chronic mild unpredictable stress (CUMS) procedure. Compound Chaigui Prescription and positive drugs (venlafaxine) were used as intervention drugs. Rat serum was analyzed by nuclear magnetic resonance (NMR) method. After data pretreatment, SIMCA-P 14.1 software was introduced for multivariate statistical analysis to verify the antidepressant efficacy of Compound Chaigui Prescription from the perspective of small molecule metabolites, and find potential disease biomarkers and drug efficacy markers. Results The CUMS depression rat model was successfully replicated. The metabolomics results showed that the levels of isoleucine, trimethylamine oxide, and creatine in the serum of CUMS-depressed rats were significantly higher than those of the model group. The levels of N-acetyl-glycoprotein, choline, and glucose were decreased with a significant difference (P < 0.05, 0.01). Conclusion The serum metabolite levels in CUMS model rats were significantly corrected after Compound Chaigui Prescription intervention. This study can provide reference for the study of antidepression mechanism of Compound Chaigui Prescription.

Target identification of endogenous metabolites and its applications in precision medicine and targeted cancer therapy / 医学研究生学报

In the past decades, the targeted therapeutic strategies of anti-cancer drugs based on metabolic regulation has been progressing. The study found that the regulation of over-activated metabolic pathways and the subsequent changes brought to metabolic homeostasis can effectively inhibit tumor growth and metastasis. However, the mechanistic link between cancer metabolism and cell fates has remained unclear. As the advancements of biological mass spectrometry and functional omics, researchers have discovered that endogenous metabolites can interact with multiple proteins as functional ligands, and thus affect the survival and proliferation of cancer cells. Nevertheless, the the direct targets and regulatory mechanisms of most functional metabolites in tumors are still unknown. The missing recognition of them has impeded further exploration of the development of precise targeted drug design based metabolic the phenomenon of tumor metabolic reprogramming. Therefore, the capability of elucidating the direct targets of endogenous metabolites in vivo not only helps to develop drugs based on the leading compounds targeting tumor metabolic, but also provides new ideas for personalized medicines of tumor patients. This review thus focuses on the characteristics of cancer metabolism and how endogenous metabolites affects tumor survival, and introduces current target identification approaches applicable to endogenous compounds, in hope to provide thoughts for developing precise treatment strategies based on cancer metabolism.

UHPLC-HRMS metabonomics to study effect of sulfur-fumigated Ophiopogonis Radix on endogenous metabolites in rats / 中国中药杂志

The project was launched to analyze the effects of sulfur-fumigated Ophiopogonis Radix on endogenous metabolites in rats by metabonomics. The preparation method of sulfur-fumigated Ophiopogonis Radix in laboratory was established. Then the blood samples of SD rats in blank group,Ophiopogonis Radix extract group and sulfur-fumigated Ophiopogonis Radix extract group were investigated by UHPLC-Q-Exactive. The differential metabolites were screened and identified by PCA(principal component analysis),OPLSDA(orthogonal partial least squares discriminant analysis) and variable importance projection(VIP),and the metabolic pathways were analyzed. Finally,a total of 15 potential biomarkers were identified. Compared with the samples of Ophiopogonis Radix extract group,sulfur-fumigated Ophiopogonis Radix mainly affected the biosynthesis and metabolism of amino acids in normal rats. Its mechanism may be related to the biosynthesis of phenylalanine,tyrosine,tryptophan and aminoacyl-tRNA as well as the metabolism of phenylalanine and tryptophan. Based on UHPLC-HRMS metabonomics,this paper discussed the effects of sulfur-fumigated Ophiopogonis Radix on endogenous metabolites in rats,which provided an idea for the metabolic study of other sulfur-fumigated traditional Chinese medicines.

Study on Tissue Distribution of A Variety of Endogenous Metabolites by Air Flow Assisted Ionization-Ultra High Resolution Mass Spectrometry Imaging / 分析化学

As a promising new molecular imaging technique,mass spectrometry imaging(MSI) has attracted more and more attention in the field of biomedicine. A method of air flow assisted ionization-ultra high resolution mass spectrometry-based mass spectrometric imaging (AFAI-MSI) was developed to profile endogenous metabolites in rat kidney tissue in this study. Rat kidneys were collected and cut into frozen tissue sections,and then were analyzed on an AFAI-MSI system in positive ion mode using acetonitrile-isopmpyl alcohol-water (4:4:2,V/V,5 μL/min) as spray solvent,N2as spray gas(0.6 MPa) and air as assisting gas (45 L/min). The mass range and resolution were set to be 70-1000 Da and 70000, respectively. As a result,a total of 38 metabolites, including organic amines, sugars, vitamins, peptides, neurotransmitters, organic acids,phospholipids,sphingolipids,glyceride,and cholesterol esters, were identified and imaged to characterize their tissue-specific distribution in kidney tissues, and some metabolites, such as choline, acetylcoline,betaine,phoshocholine,and glycerophosphocholine were found to have distinct distribution along the cortex-medulla axis,which may be involved in the formation of osmotic pressure gradient in the kidney. The proposed ultra high resolution mass spectrometry based AFAI-MSI method could work without sample pretreatment, showed high sensitivity and wide metabolite coverage, and was expected to provide a new analytical approach for the research of in situ characterization and metabolic regulation mechanism of endogenous metabolites in kidney.

Metabolomics approach to evaluation of plateau hypoxia / 中草药

Under plateau environment, inadequate oxygen makes people breathe less oxygen, reducing the level of oxygen metabolism and energy supply in the body. Subsequently, the peripheral circulation, the contractile efficiency of myocardial cells, the pump of blood stream, the flow rate of blood in various tissues, and the excretion rate of waste in the body could be greatly reduced, which are key reasons for causing plateau disease. Due to the reason that many metabolic pathways are affected in vivo, the level of endogenous small molecular metabolites can also be changed greatly. Therefore, metabolomics has been gradually applied to the study of plateau diseases, pathogenesis and even pharmacodynamics. This article summarizes the pathogenesis of plateau hypoxia and metabolomics of the associated therapeutic agents based on the preclinical and clinical research reviewed from the altitude sickness-associated metabolic research literature at home and abroad. Previous studies have confirmed that the endogenous metabolites and metabolic pathways altered significantly under plateau hypoxia, and some drugs showed a certain regulatory effect on the pathway metabolism. Moreover, the article summarizes the problems existing in the application of metabolomics in plateau hypoxia disease and the prospect of its future application. It was suggested that metabolomics was a promising tool for the study on the mechanism and the primary assessment of candidate drugs for plateau disease.

1H-NMR-based metabonomics studyon urine of rat with Spleen-Qi deficiency pattern / 中国药理学通报

Aim To establish the rat model of Spleen-Qi deficiency, analyse the metabolic pathways and investigate the connection between the changed urinary metabolites and Spleen-Qi deficiency, in order to explore the potential mechanisms of Spleen-Qi deficiency.Methods With the binding methods of diarrhea induced by bitter and cold, abnormal of starvation and excessive tiredness, the rat Spleen-Qi deficiency model was established.Then the activity of creatine phosphokinase(CPK) was detected.The endogenous metabolites in the urine were detected by NMR, and the data were analyzed with multivariate and statistical methods.Then the metabolites were selected that could be clearly distinct in the two groups with the fold change value(>1.2) and the P<0.05 of Student′s t-test.Both the pathway analysis and enrichment analysis were performed with Metabo Analyst 3.0.Results Compared with the normal rats, the activity of CPK decreased significantly in model rats(P<0.05).A significant separation appeared in the principal components analysis(PCA) score plot when the control group and the model group were compared, indicating that the Spleen-Qi deficiency model was successfully duplicated.The 33 differential metabolites, which mainly involved in the metabolic pathways, were distinguished from the comparision of Spleen-Qi deficiency model group and control group.The metabolic pathways was related to energy metabolism, amino acid metabolism, nucleotide metabolism and disturbance of gut microbes.Conclusions The main energy metabolic pathways (tricarboxylic acid cycle, glycolysis and liquid oxidation) may be disturbed in Spleen-Qi deficiency rats.The energy supply function is suppressed, which leads to the fatigue and weight loss in rats.

Effect of Tongxie Yaofang on endogenous metabolites in serum of IBS model rats / 中国中药杂志

To evaluate the effect of Tongxie Yaofang on cardiac endogenous metabolism in irritable bowel syndrome(IBS) rats by using metabolomics method, find its potential biomarkers, analyze the metabolic pathways, and explore the pharmacological effects, mechanisms of action and syndrome essence of syndrome model. Forty Wistar rats were used to establish IBS models, and then randomly divided into four groups： model control group and Tongxie Yaofang treatment groups (high, medium, low dose). Another 10 rats were used as normal group. The rats in Tongxie Yaofang-treated(low, medium and high dose) groups were orally administrated with Tongxie Yaofang extracts once a day for 2 weeks, respondingly with the doses of 0.203,0.406,0.812 g•mL⁻¹. The rats in normal group and model control group were given with equal volume of saline once a day for 2 weeks. On the 0 and 15th days, serum was collected and each sample extract was analyzed by UPLC-Q-TOF-MS. Eight potential biomarkers were identified and 8 major metabolic pathways were found to be related with IBS diseases neurotransmitter metabolism, inflammatory immunity, brain function and energy metabolism, etc. Tongxie Yaofang had certain pharmacological effects on IBS, and its mechanism may be related to serotonergic synapse, tryptophan metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and so on, which might be the biological basis of IBS liver-spleen deficiency syndrome.

Effect of heat-reinforcing needling on serum metabolite profiles in rheumatoid arthritis rabbits with cold syndrome / 中国针灸

<p><b>OBJECTIVE</b>To explore heat-reinforcing needling for the metabolite profiling changes in serum of rheumatoid arthritis (RA) rabbits with liquid chromatograph-mass spectrometer (LC-MS) technique, and to investigate its mechanisms.</p><p><b>METHODS</b>Forty clean purple blue rabbits were randomized into a normal group, a model group, a reinforcing-reducing needling (RRN) group, a twirling-reinforcing needling (TRN) group, and a heat-reinforcing needling (HRN) group, 8 cases in each group. RA rabbits with cold syndrome were made with ovalbumin and freezing except those in the normal group. No treatment was given in the normal and model groups. The corresponding manipulations for 7 days were applied at "Zusanli" (ST 36) in the three acupuncture groups, 30 min a time, once a day. After intervention the pain threshold and the local skin temperature of each group were observed. Fresh serum from heart was collected for metabonomics detection. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were adopted. Several metabolites were screened by the variable importance in the projection values (VIP>1) andvalue (<0.05).</p><p><b>RESULTS</b>The pain threshold and the local skin temperature in the model group were lower than those in the normal group (both<0.05). The pain threshold and the local skin temperature in the three acupuncture groups were higher than those in the model group after intervention (all<0.05), which were better in the HRN group than those in the RRN and TRN groups (all<0.05). The serum metabolites of carnitine, LysoPC (14∶0), LysoPC (18∶3), LysoPE (0∶0/20∶5), LysoPE (0∶0/22∶1), decylic acid, stearic acid and lactic acid in the model group increased compared with those in the normal group, and other metabolites decreased, including leucine, valine, glutamine, pyroglutamic acid, α-ketoglutaric acid, succinic acid, fumaric acid, malic acid, galactose, mannose. Those metabolites were correlated fatty acid, amino acid, citric acid cycle, and glucose metabolism. The metabolites above-mentioned in the three acupuncture groups were regulated in various degrees (all<0.05). Lactic acid decreased and succinic acid, fumaric acid, malic acid, galactose, mannose increased more obviously in the HRN group than those in the RRN and TRN groups.</p><p><b>CONCLUSION</b>The specificity of heat-reinforcing needling for RA presents the regulation for citric acid cycle and glucose metabolism.</p>

Study on mechanism of nourishing blood and smoothing liver effects of Paeoniae Radix Alba based on metabolomics information / 中草药

Objective: To investigate the nourishing blood and smoothing liver effects of Paeoniae Radix Alba (PRA) based on metabolomics information. Methods: The stagnation of liver qi and blood deficiency syndrome rats model was established by chronic restraint stress combined with radiation. Using LC/MS method as the core technology, the principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA) as the main data analysis methods, endogenous metabolites were screened in the model rats to study the intervention mechanism of PRA. Results: Through the impact of phosphatidylcholine, lysophosphatidylcholine, ceramide, deoxycytidine, betaine, and other 21 kinds of small molecular metabolites, PRA had a certain callback effect on the disturbance of metabolic trajectory, which can improve the state of stagnation of liver qi and blood deficiency induced by external stimulating factors (such as irradiation, restraint, and loneliness). Conclusion: The nourishing blood and smoothing liver effects of PRA may be related to the sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and alpha-linolenic acid metabolism.

Mechanisms of tonifying blood with Lvjiao Buxue Granules studied by1H-NMR metabolomics / 中草药

Objective: To explore the change of endogenous metabolites in serum of rats with erythronoclastic anemia and the intervention of Lvjiao Buxue Granules by using 1H-NMR metabonomics coupled with multivariate statistical analysis. Methods: Acetylphenylhydrazine was used to establish the rat model of erythronoclastic anemia and after a week the rats except control and model groups were given to Lvjiao Buxue Granules (8 g/kg) separately once daily for two weeks. While the rats in the control and model groups were ig given equivalent distilled water respectively. The endogenous metabolites in serum from all of rats were analyzed by 1H-NMR coupled with multivariate statistical analysis. Results: Compared with the control group, the levels of lipids, lactic acid, and acetone in serum of rats in the model group increased while the levels of alanine, valine, creatinine, phosphocholine, glycerophosphocholine, oxidation of three methyl ammonium, glycine, and arginine were decreased. The levels of these endogenous metabolites with significant difference were reversed to normal by ig asminstration of Lvjiao Buxue Granules. Conclusion: The mechanism of Lvjiao Buxue Granules on tonifying blood is involved in the pathway of energy metabolomic, lipid metabolism, and intestinal bacteria metabolism.

1H-NMR metabonomic study on fecal of chronic unpredicted mild stress model of depression in rats / 中草药

Objective: To obtain the potential biomarkers of chronic unpredictable mild stress (CUMS) rats, the change of endogenous metabolites in the faeces of CUMS rats was analyzed using 1H-NMR coupled with metabonomics. Methods: CUMS procedure was conducted for four weeks, CUMS rat model was duplicated, and the faeces of rats was collected at the end of the procedure. The change of endogenous metabolites in faeces was analyzed using 1H-NMR coupled with multivariate statistical analysis. Results: The PLS-DA scores plot demonstrated that behavior indexes of rats in the control group were significantly different from these of rats in CUMS group, suggesting the CUMS model of depression in rats was prepared successfully. Thirty metabolites were identified in the 1H-NMR spectra of faeces, the concentration of glutamine, lactate, and aspartate was increased while that of β-glucose, uracil, tyrosine, and phenylalanine was decreased in CUMS model group with the significant difference compared with the control group (P < 0.05, 0.01). Conclusion: By researching the change of endogenous metabolites in the faeces of CUMS rats, the potential biomarkers in the faeces of CUMS rats are picked up to lay the foundation for the study on the depression pathogenesis and clinical diagnosis.