Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 221
Filter
1.
Article in Chinese | WPRIM | ID: wpr-928189

ABSTRACT

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.


Subject(s)
Animals , Biomarkers , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacology , Estazolam , Hippocampus/metabolism , Metabolomics/methods , Rats , Sleep , Sleep Initiation and Maintenance Disorders/drug therapy
2.
Article in Chinese | WPRIM | ID: wpr-928145

ABSTRACT

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.


Subject(s)
Animals , Bile Acids and Salts , Cholestasis/drug therapy , Chromatography, Liquid , Medicine, Tibetan Traditional , Metabolomics , Mice
3.
Article in Chinese | WPRIM | ID: wpr-928093

ABSTRACT

Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1β and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.


Subject(s)
Animals , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal , Hypothalamo-Hypophyseal System , Metabolomics/methods , Pituitary-Adrenal System , Rats , Sleep Initiation and Maintenance Disorders/drug therapy , Tandem Mass Spectrometry
4.
Article in Chinese | WPRIM | ID: wpr-927978

ABSTRACT

Syndrome is a nonlinear "internal-excess external-deficiency", "dynamic spatial-temporal" and "multi-dimensional" complex system and thus only by using a versatile method can the connotation be expounded. Metabonomics, which is dynamic, holistic, and systematic, is consistent with the overall mode of traditional Chinese medicine(TCM)(holistic view and syndrome differentiation and treatment). Therefore, metabonomics is very important for the research on the differentiation, material basis, and metabolic pathways of syndromes, and efficacy on syndromes. This study reviewed the application of metabonomics in the study of TCM syndromes in recent years, which is expected to objectify the research on TCM syndromes.


Subject(s)
Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Metabolomics , Syndrome
5.
Article in Chinese | WPRIM | ID: wpr-927941

ABSTRACT

Chinese medicine processing is a procedure to process medicinal materials under the guidance of traditional Chinese medicine(TCM) theories by using unique methods in China. The medicinal materials can only be used clinically after proper processing. With the development of the modernization of TCM, it is difficult to solve the problems in the inheritance, development, and internationalization of Chinese medicine processing. Metabonomics, a new omics technology developed at the end of the last century, is used to infer the physiological or pathological conditions of the organism with the methods such as NMR and LC-MS via investigating the changes in endogenous small molecule metabolic network after the organism is stimulated by external environment. Metabonomics coincides with the holistic view of TCM because it displays the characteristics of integrity, comprehensiveness, and dynamics, and it has been widely applied in the field of Chinese medicine processing in recent years. This study summarized the application of metabonomics in the processing mechanism and quality control of Chinese medicine processing and prospected the development of this technology in the field of Chinese medicine processing.


Subject(s)
Chromatography, Liquid , Drugs, Chinese Herbal , Mass Spectrometry , Medicine, Chinese Traditional , Metabolomics/methods , Quality Control
6.
Article in English | WPRIM | ID: wpr-922581

ABSTRACT

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.


Subject(s)
Blood Platelets , Hemostasis , Platelet Activation , Proteomics , Technology
7.
Acta Pharmaceutica Sinica ; (12): 1387-1395, 2022.
Article in Chinese | WPRIM | ID: wpr-924766

ABSTRACT

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

8.
China Pharmacy ; (12): 1094-1101, 2022.
Article in Chinese | WPRIM | ID: wpr-923758

ABSTRACT

OBJECTIVE To study the effect of Longsheng zhi capsule on lear ning and memory ability of vascular dementia model rats and explore its mechanism based on metabonomics. METHODS Totally 90 SD rats were randomly divided into sham operation group ,model group ,Dihydroergotoxin mesylate tablet group (positive control ,0.54 mg/kg),Longshengzhi capsule high-dose,medium-dose and low-dose groups (2.16,1.08 and 0.54 g/kg),with 15 rats in each group. In addition to sham operation group (only threading without ligation ),the vascular dementia model was prepared by permanent ligation of bilateral common carotid arteries in each group ,which was administered by gavage for 28 d. Morris water maze test was used to determine the learning and memory ability of rats ;hematoxylin eosin (HE)staining was used to observe the histopathological changes of hippocampus;the serum levels of superoxide dismutase (SOD),malondialdehyde(MDA)and glutathione peroxidase (GSH-Px) were detected ;the serum metabolic map was analyzed by ultra high performance liquid chromatography quadrupole time of flight tandem mass spectrometry (UPLC-Q-TOF/MS),the specific metabolites were screened by multivariate statistical analysis ,and the metabolic pathway was enriched and analyzed. RESULTS Morris water maze test showed that compared with model group ,the escape latency of rats in each administration group was significantly shortened ,the number of crossing the platform was significantly increased ,and the residence time in the target quadrant was significantly prolonged (P<0.01 or P< 0.05). The results of serum biochemical indexes showed that compared with model group , the s erum level of SOD increased significantly in Dihydroergotoxine mesylate tablet group and Longshengzhi capsule high-dose group ,the serum level of GSH-Px increased significantly while the MDA level decreased significantly in each administration group (P<0.05 or P<0.01). HE staining showed that Longshengzhi capsule could improve the histopathological damage of hippocampus in vascular dementia model rats. A total of 14 differential metabolites were screened and identified by UPLC-Q/TOF-MS and orthogonal partial least squares discriminant analysis model (VIP>1 and P<0.05). The results of metabolic pathway enrichment analysis showed that the metabolic pathways involved in vascular dementia in rats mainly included vitamin B 6 metabolism,fatty acid metabolism and steroid hormone biosynthesis. CONCLUSIONS Longshengzhi capsule can improve the learning and memory ability of rats caused by vascular dementia. Its effect may be related to improving the oxidative stress injury caused by lipid accumulation in the process of vascular dementia. The metabolic pathways involved mainly include vitamin B 6 metabolism,fatty acid metabolism and steroid hormone biosynthesis.

9.
Acta Pharmaceutica Sinica ; (12): 757-765, 2022.
Article in Chinese | WPRIM | ID: wpr-922876

ABSTRACT

UHPLC-Q-TOF/MS metabonomics technology was used to clarify the metabolic regulation pathways by which Platycodon total saponins (PTS) exert antitussive and expectorant effects in a mouse cough model, in which coughing is induced by concentrated ammonia, and in a phenol red excretion model. After approval by the Experimental Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235), the mice were randomly divided into a normal group, a model group, a positive drug group and a PTS group. Endogenous metabolites in mouse serum were identified by UHPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for multivariate analysis. Metabolic pathways were analyzed by the Metaboanalyst platform. The results show that PTS can significantly prolong the cough latent period and cough frequency of mice, and significantly increase phenol red excretion. UHPLC-Q-TOF/MS identified 19 metabolites related to cough, and PTS significantly decreased 16 of them; 17 metabolites related to expectoration were identified, and PTS decreased the levels of all. Metabolic pathway analysis showed that linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism were the main pathways involved in serum metabolite changes in this mouse cough model. Linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism and α-linolenic acid metabolism were the main pathways involved in serum metabolite changes in the phenol red excretion model. This study is the first to elucidate the regulation of antitussive and expectorant metabolic pathways and the effect of PTS on these pathways.

10.
Chinese Critical Care Medicine ; (12): 1021-1024, 2021.
Article in Chinese | WPRIM | ID: wpr-909447

ABSTRACT

Bronchial asthma (asthma) is a complex heterogeneous disease, with a high rate of missed diagnosis and misdiagnosis. Repeated attacks of bronchial asthma can cause complications such as chronic obstructive pulmonary disease, emphysema, and pulmonary heart disease. In recent years, mass-spectrometry-based metabolomics has developed rapidly. It can sensitively identify metabolic fluctuations and pathological changes in patients with asthma. By analyzing the molecules produced by various metabolic pathways, it can help us to find relevant biomarkers and provide a better method for early diagnosis and severity assessment of asthma. We reviewed and analyzed the literature of metabolomics technology in disease progression, early diagnosis and severity assessment, so as to provide reference for asthma research.

11.
Chinese Journal of Endemiology ; (12): 871-876, 2021.
Article in Chinese | WPRIM | ID: wpr-909115

ABSTRACT

Objective:To screen differential metabolites and metabolic pathways in urine of adult patients with Kashin-Beck disease (KBD), so as to provide scientific basis for finding specific biomarkers and pathogenesis of KBD.Methods:In Yongshou County, the KBD area in Shaanxi Province, adult KBD patients were selected as the case group, and healthy people without clinical symptoms of KBD were selected as the control group in the same disease area. The subjects' fasting mid-morning urine was collected, and liquid chromatography-mass spectrometry (LC-MS) technology was used to detect small-molecule metabolites in the urine. Multivariate statistical analysis [partial least square discriminant analysis (PLS-DA)] and comparison with KEGG and human metabonomics database (HMDB) were used to identify and screen differential metabolites and metabolic pathways in KBD patients.Results:A total of 58 subjects were included, 39 cases in the case group, including 23 males and 16 females; the age was (61.2 ± 7.8) years old; the body mass index was (22.7 ± 6.5) kg/m 2. There were 19 cases in the control group, including 10 males and 9 females; the age was (50.0 ± 9.0) years old; the body mass index was (24.3 ± 5.5) kg/m 2. Three first-order differential metabolites (HT-2 toxin, T-2 tetraol and seleno-adenosine selenomethionine) were identified and screened, which were highly related to the pathogenesis of KBD, and all were down-regulated. There were 38 second-order differential metabolites, among them, 10 were up-regulated and 28 were down-regulated. Nine differential metabolic pathways were screened, mainly involving amino acid metabolism, lipid metabolism and energy metabolism. Conclusions:The urine metabolism profiles of adult KBD patients and healthy people are significantly different, mainly involving amino acid metabolism, lipid metabolism and energy metabolism. The first-order differential metabolites HT-2 toxin, T-2 tetraol and seleno-adenosine selenomethionine are highly correlated with the pathogenesis of KBD.

12.
Chinese Journal of Endemiology ; (12): 775-780, 2021.
Article in Chinese | WPRIM | ID: wpr-909096

ABSTRACT

Objective:To explore the serum different metabolites in population of dietary intervention with high iodine.Methods:Thirty-eight healthy volunteers were recruited in Harbin Medical University, all women, aged > 20 years. Dietary intervention was carried out by eating iodine-rich food (kelp) for 11 consecutive days. The effect of intervention was evaluated through urinary iodine test. Peripheral blood was collected, the metabolic alterations associated with high iodine intake before and after intervention were investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF MSMS). Multivariate statistical analysis was used to screen potential biomarkers. And disturbed metabolic pathway analysis was performed.Results:The medians urinary iodine before and after intervention were 129.48 and 795.94 μg/L, respectively. A total of 20 serum biomarkers were screened and their chemical structures were identified. Glycerol phospholipid metabolic pathway, tryptophan metabolic pathway and pentose and glucuronate interconversions pathway were closely related with high iodine intake (impact value > 0.1).Conclusions:After the intervention of high iodine diet, there are obvious differential metabolites in peripheral blood, which may be used as biomarkers for evaluation of population iodine nutrition. High iodine intake has an impact on metabolic pathway of glycerol phospholipid in human body.

13.
Article in Chinese | WPRIM | ID: wpr-906522

ABSTRACT

Objective:To investigate the intervention of <italic>Hedyotis diffusa</italic> (HDW) on colitis associated cancer (CAC) model mice and explore its mechanism. Method:The CAC mouse model was established by synergistic action of azoxymethane (AOM) and dextran sulfate sodium (DSS). The intervention of HDW on CAC mice was evaluated by disease activity index (DAI), colonic tissue morphology, pathological injury score and tumorigenesis rate. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and multivariate statistical analysis were used to analyze the metabonomics of mice serum and to explore the mechanism of HDW intervention on CAC. Result:HDW could significantly improve the general condition of CAC mice, decrease DAI, colon gross morphological score, histopathological score and tumorigenesis rate. Compared with the normal group, 38 kinds of differential metabolites were screened in the model group, including 11 potential biomarkers, involving 11 main metabolic pathways. HDW could significantly regulate 9 kinds of differential metabolites [niacinamide, uridine, 4-pyridoxic acid, LysoPC (18∶0), LysoPE (0∶0/20∶0), myo-inositol, purine, sphinganine 1-phosphate and tetradecanedioic acid] in the model group, including 2 kinds of potential biomarkers (myo-inositol and niacinamide), and HDW could regulate nicotinate and nicotinamide metabolism and inositol phosphate metabolism. Conclusion:HDW has a therapeutic effect on CAC, which may be achieved by regulation of energy metabolism and glucose metabolism.

14.
Article in Chinese | WPRIM | ID: wpr-906489

ABSTRACT

Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol (PTZ)-kindled epileptic rats treated with Chloriti Lapis. Method:The epileptic animal model in rats was established by PTZ kindling, and the rats were divided into the control group, model group, carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF-MS), and the experimental results were statistically analyzed by partial least squares-discriminant analysis (PLS-DA) and SPSS 18.0. Result:The metabolic fingerprints and metabolic profiles of the rat brain tissue were established, which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover, the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened, including phosphatidylserine (PS) (18∶0/18∶0), <italic>L</italic>-glutamic acid, docosahexaenoyl ethanolamide, arachidonic acid, glucosylsphingosine, cholestane-3,7,12,24,25-pentol and lysophosphatidylcholine (LysoPC) (P-18∶0). Except for docosahexaenoyl ethanolamide and LysoPC (P-18∶0), Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats, and 3 important metabolic pathways (pathway impact>0.1), namely, <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism, alanine, aspartate and glutamate metabolism, and arachidonic acid metabolism, among which <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view, Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats, which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue, so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.

15.
Article in Chinese | WPRIM | ID: wpr-906305

ABSTRACT

Objective:To investigate the inhibitory effects and mechanism of Reyanning mixture (RYN) combined with linezolid (LNZ) against methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA) and its biofilm. Method:The minimum inhibitory concentrations (MICs) of RYN and LNZ against MRSA were determined by microdilution assay. The microplate method was used to detect the changes in viable count before and after MRSA administration at four time points (0, 6, 12, 24 h) in the process of biofilm growth. The morphological changes of MRSA after 24 h were observed by scanning electron microscope. Metabonomic technique was applied to analyze the changes in terminal metabolites of endogenous small molecules from MRSA treated by the two drugs at four time points. Result:The MICs of RYN and LNZ were 1/2 of the stock solution concentration and 4 mg·L<sup>-1</sup>, respectively. The inhibitory effect of LNZ (2 mg·L<sup>-1</sup>) against viable bacteria at 0 h was better than that of 1/16 RYN. At 6, 12, 24 h, 1/16 RYN was superior to LNZ in inhibiting MRSA. The inhibitory effects of RYN combined with LNZ were better than those of RYN or LNZ alone at the four time points. RYN combined with LNZ caused more severe damages to the morphological structure of MRSA biofilm at 24 h than RYN or LNZ alone. Cyclic adenosine monophosphate (cAMP), adenosine diphosphate (ADP)-<italic>D</italic>-ribose and 2-methylbutanoyl-coenzyme A (2M-CoA), as the metabolites related to biofilm formation, were immune to LNZ, but 2M-CoA and ADP-<italic>D</italic>-ribose were influenced by RYN at 12 h and 24 h. The combined use of RYN and LNZ interfered with the three metabolites at 24 h. <italic>L</italic>-tryptophan, phenylpyruvic acid, cytidine and sebacic acid were the pharmacometabolic markers of LNZ, and the related biological pathways were phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism. Four metabolites such as<italic> L</italic>-histidine, uric acid, and <italic>L</italic>-lysine were the pharmacometabolic markers of RYN, with phenylalanine metabolism and aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis confirmed as the related biological pathways. Nine metabolites such as <italic>L</italic>-tryptophan,<italic> L</italic>-lysine, and sphingosine-1-phosphate were responsible for the efficacy of RYN combined with LNZ. The related biological pathways involved aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, novobiocin biosynthesis, and tyrosine metabolism. Conclusion:RYN combined with LNZ better exerts the inhibitory effects against MRSA at each time point of its biofilm formation, which is attributed to cAMP metabolism. The synergistic effect resulted from aminoacyl-tRNA biosynthesis and phenylalanine, tyrosine and tryptophan biosynthesis. RYN combined with LNZ can serve as a potentially effective solution to MRSA infection.

16.
Article in Chinese | WPRIM | ID: wpr-904329

ABSTRACT

@#The effect of sodium salicylate on the endogenous metabolism of hair cell-like cells (HEI-OC1).of mice was analyzed based on liquid chromatography-quadrupole time of flight mass spectrometry (LC-Q-TOF/MS).Firstly, HEI-OC1 cells were treated with different concentrations of sodium salicylate, and cell survival was examined by the CCK-8 method. Next, sodium salicylate was administered for different duration to observe the changes in cell morphology. Inter-group differential metabolites were screened out, and the associated metabolic pathways were analyzed based on metabonomic technology.Results showed that sodium salicylate could significantly inhibit the survival rate of HEI-OC1 cells, and that, as the concentration increased, the inhibitory effect became stronger. Also, the cell morphology could be elongated after administration and return to normal after withdrawal.Eighteen differential metabolites such as orotic acid, uridine and aspartic acid were screened out after treatment of sodium salicylate, which mainly involving two possible metabolic pathways, namely the metabolism of alanine, aspartic acid and glutamic acid, and that of pyrimidine.In summary, the application of metabolomics technology to evaluate the effect of sodium salicylate on hair cells from the microscopic perspective can provide new ideas for the study of sodium salicylate ototoxicity and development of tinnitus.

17.
Article in Chinese | WPRIM | ID: wpr-887993

ABSTRACT

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.


Subject(s)
Animals , Biomarkers , Blood Platelets , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacology , Metabolomics , Rabbits , Technology
18.
Article in Chinese | WPRIM | ID: wpr-887952

ABSTRACT

In order to study the regulation mechanism of secondary metabolites biosynthesis in Lonicera macranthoides, the key genes involved in the regulation of biosynthesis and the mechanism of differential metabolites were explored. In this study, high-throughput sequencing technology was used for transcriptome sequencing of L. macranthoides at different development stages. By using Liquid chromatography-tandem mass spectrometry(LC-MS/MS) technology, the laws of qualitative, quantitative and synthetic accumulation of its metabolites were studied, and the key enzyme genes for the biosynthesis of phenolic acid and flavonoids were screened out according to the differentially expressed genes. A total of 111 differentially accumulate metabolites(DAM) and 6 653 differentially expressed genes(DGE) were obtained by metabonomics and transcriptomics analysis. The metabolites and key enzyme genes in the Erqing(KE) were significantly different from those in the Dabai(KD) and Yinhua(KY) stages. In the phenylalanine biosynthesis pathway, the ion abundance of chlorogenic acid, naringin, quercetin, rutin, coniferol and other metabolites decreased with the development of flowers, while the ion abundance of ferulic acid, coumarin and syringoside increased with the development of flowers. Key enzyme genes such as CHS, HCT, CCR, FLS and COMT positively regulate the downstream metabolites, while PAL, C4H and 4CL negatively regulate the downstream metabolites. This study provides candidate genes and theoretical basis for the further exploration of key enzymes in the biosynthesis of secondary metabolites and for the regulation of the accumulation of secondary metabolites in L. macranthoides by molecular biological methods.


Subject(s)
Chromatography, Liquid , Flowers/genetics , Lonicera/genetics , Metabolomics , Proteomics , Tandem Mass Spectrometry
19.
Acta Pharmaceutica Sinica ; (12): 2410-2418, 2021.
Article in Chinese | WPRIM | ID: wpr-886958

ABSTRACT

Metabonomics technology was employed to investigate and identify the mechanisms and metabolic pathways of the crude and wine-processed Fructus Corni extracts on anti-hepatic fibrosis effects in rats, and to compare and analyze the potential mechanism of enhanced interference of the wine-processed Fructus Corni on hepatic fibrosis effects in rats. The rats were randomly divided into the blank control group, the model group, the colchicine group, the crude Fructus Corni groups with low, medium, and high-doses, and the wine-processed Fructus Corni groups with low, medium, and high-doses, and there were six rats in each group. The hepatic fibrosis model was established by subcutaneous injection of 40% carbon tetrachloride, and the intragastric administration was performed at the third week of modeling. The blood and liver samples of rats were taken and carried out for pharmacodynamic index detection and UHPLC-Q-TOF-MS/MS analysis after intragastric administration for six weeks. The results of pharmacodynamic investigation showed that both the crude and wine-processed Fructus Corni had the effects of anti-hepatic fibrosis in rats. Metabonomics analysis indicated that, compared to the blank control group, the twenty-four potential biomarkers related to hepatic fibrosis were screened and identified in the model group, which mainly involved in primary bile acid metabolism, glycerol phospholipid metabolism, pentose and glucuronide metabolism, retinol metabolism, and arachidonic acid metabolism. The crude and wine-processed Fructus Corni extracts had different degrees of callback effects on the ten of the above potential biomarkers, and the effect of wine-processed Fructus Corni was better than that of crude one. The present study clarifies the mechanism of enhanced efficiency of wine-processed Fructus Corni from the perspective of plasma metabolism, and provides the theoretical foundation for further development and clinical application of Fructus Corni.

20.
Article in Chinese | WPRIM | ID: wpr-921637

ABSTRACT

The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.


Subject(s)
Animals , Antidepressive Agents , Drugs, Chinese Herbal , Metabolomics , Paeonia , Powders , Rats
SELECTION OF CITATIONS
SEARCH DETAIL