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ObjectiveTo explore the mechanism of Xueniao capsule in the treatment of acute pyelonephritis (APN) by network pharmacology and experimental verification. MethodThe effect of Xueniao capsule on APN was investigated based on the APN model in rats. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Chemistryl Database, and SymMap were searched for the chemical components of Smilacis Chinae Rhizoma,Coicis Semen, and Trachycarpi Petiolus. The target information of the components was collected from PharmMapper and SwissTargetPrediction, and disease target information from Therapeutic Target Database (TTD), DrugBank, DisGeNET, GeneCards, and Online Mendelian Inheritance in Man(OMIM). The key genes of Xueniao capsule for APN underwent Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses by Metascap. Real-time quantitative polymerase chain reaction (PCR) and Western blot were employed to verify the prediction results. ResultCompared with the blank group and the sham operation group, the model group showed an increased ratio of the left kidney to the right kidney and organ index(P<0.05, P<0.01),up-regulated white blood cells (WBC),neutrophils (NEUT),monocytes (MONO), and lymphocytes (LY)(P<0.05, P<0.01), and elevated levels of nuclear factor-κB(NF-κB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)(P<0.05, P<0.01). Compared with the model group, the norfloxacin group, the low- and high-dose Xueniao capsule groups showed a decreased ratio of the left kidney to the right kidney and organ index(P<0.05, P<0.01), dwindled levels of WBC, NEUT, MONO, and LY(P<0.05, P<0.01), and reduced levels of NF-κB, IL-6, and TNF-α(P<0.05, P<0.01). The medium-dose Xueniao capsule group showed a decreased ratio of the left kidney to the right kidney and organ index(P<0.05, P<0.01), reduced levels of WBC, NEUT, MONO, and LY(P<0.05, P<0.01), and dwindled levels of IL-6 and TNF-α(P<0.05, P<0.01). Network pharmacological analysis revealed 17 active compounds from Smilacis Chinae Rhizoma, 18 active compounds from Coicis Semen, six active compounds from Trachycarpi Petiolus, and 39 key genes for the treatment of APN in Xueniao capsule. GO enrichment analysis demonstrated 704 biological processes, 22 cellular components, and 59 molecular functions. Sixty-two pathways were enriched in KEGG enrichment analysis. The experimental verification results showed that compared with the blank group, the model group showed increased mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 1 (MAPK1)/extracellular signal-regulated protein kinase 2 (ERK2),phosphoinositide 3 kinase (PI3K),protein kinase B2(Akt2),Janus kinase 2 (JAK2),and signal transducer and activator of transcription 3 (STAT3)and protein expression of PI3K, Akt2, JAK2, and STAT3 (P<0.05, P<0.01). Compared with the model group, the low-dose Xueniao capsule group showed decreased mRNA expression of MAPK1, PI3K, JAK2, and STAT3 and protein expression of PI3K, JAK2, and STAT3 (P<0.05, P<0.01). The medium-dose Xueniao capsule group showed decreased mRNA expression of MAPK1, PTGS2, PI3K, JAK2, and STAT3, and protein expression of PI3K, JAK2, and STAT3 (P<0.05, P<0.01). The high-dose Xueniao capsule group showed reduced mRNA expression of PTGS2, MAPK1, PI3K, Akt2, JAK2, and STAT3 and protein expression of PI3K, Akt2, JAK2, and STAT3 (P<0.05, P<0.01). ConclusionXueniao capsule has a certain curative effect on APN via multiple targets and multiple pathways. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and the JAK2/STAT3 signaling pathway.
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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 , Rats , Biomarkers , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacology , Estazolam , Hippocampus/metabolism , Metabolomics/methods , Sleep , Sleep Initiation and Maintenance Disorders/drug therapyABSTRACT
Serum pharmacochemistry of traditional Chinese medicine(TCM) is a new subject based on the identification of migrating components in serum after oral administration of TCM.After more than 20 years of development,serum pharmacochemistry of TCM has been widely recognized and applied by researchers.Based on the references related with the serum pharmacochemistry from these years,the research summarized the methods of serum pharmacochemistry of TCM,for example,selection of experimental animals,preparation of gastric irrigation,design of drug administration scheme,method and time of adoption blood,pretreatment of serum containing drug,as well as analysis of serum sample.In addition,the paper will emphatically introduce the application of serum pharmacochemistryof TCM,which includes clarifying the substance basis of Chinese medicine,establishing the quality standard of TCM,and clarifying the compatibility of compound Chinese medicine.At the same time,we will through some existing problems to look forward to the future of serum pharmacochemistryof TCM,so that people can have a comprehensive understanding of serum pharmacochemistryof TCM,hoping to lay a foundation for the further application of this method in TCM research.
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Objective:The effect of processing on promoting digestion of Crataegi Fructus was investigated by the method of serum metabonomics based on 1H-NMR and the analysis of traditional biochemical indexes. Method:The dyspepsia model was induced by high protein and calorie diet. The small intestine propulsive rate in mice and the hormone level in rat gastrointestinal tract were used as pharmacodynamic indexes. After administration of Crataegi Fructus, fried and charred Crataegi Fructus, the changes of serum metabolites were analyzed by 1H-NMR technique combined with multivariate statistical analysis, so as to compare the therapeutic effects of each processed products on rats with dyspepsia model. Result:Each processed products group of Crataegi Fructus could improve the ability of intestinal propulsion and gastric emptying, especially in charred Crataegi Fructus group, caused by dyspepsia. The serum metabonomics proved that there were significant metabolic differences between the model group and the blank group. A total of 13 biomarkers related to dyspepsia, covering 3-hydroxybutyric acid, glycerophosphoryl choline (GPC), N-acetylglycoprotein, O-acetylglycoprotein, trimethylamine oxide (TMAO), alanine, acetic acid, glutamic acid, glutamine, creatine, leucine, lactic acid and glucose, were screened on the grounds of VIP value of S-plot, single factor ANOVA and area under receiver operating characteristic curve (ROC curve) (AUC). The metabolite composition of each administration group was the same except that the callback tendency of O-acetylglycoprotein, glutamine and GPC in charred Crataegi Fructus group was closer to that in the blank group. Conclusion:There are differences in the effect of promoting digestion to eliminate stagnation among processed products of Crataegi Fructus, charred Crataegi Fructus is more effective in improving dyspepsia, which may play a role in regulating gastrointestinal motility and energy metabolism.
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Based on1 H-NMR metabonomics,the effects of Codonopsis pilosula,rice-fried C. pilosula and honey-fried C. pilosula on spleen-asthenia rats were compared,and the mechanism was discussed in this study. The rat model of spleen deficiency was established by weight-bearing swimming and fasting every other day. The effects of different processed products of C. pilosula on the body weight and swimming time of rats were observed. At the end of administration,the gastrocnemius muscle of the right leg of rats was collected and detected by1 H-NMR,and the mechanism of different processed products of C. pilosula in improving spleen deficiency was preliminarily investigated by multivariate statistical analysis. The results showed that C. pilosula,honey-fried C. pilosula and rice-fried C. pilosula could significantly prolong the swimming time( P<0. 05). There was no significant difference in the body weight of rats with spleen deficiency. The results of metabonomics showed that honey-processed C. pilosula could significantly decrease levels of leucine,isoleucine,alanine,acetate,glutamate,succinate,anserine,dimethylamine,dimethylglycine,creatine,phosphorylcholine,glycerophosphorylcholine,taurine,inosine,fumate,hypoxanthine and lactate,but increase levels of glucose,glycine,compared with model group. Therefore,honey-fried C. pilosula has the best efficacy on spleen deficiency syndrome in rats by regulating glycometabolism,amino acid metabolism,lipid metabolism and nucleotide metabolism.
Subject(s)
Animals , Rats , Codonopsis , Magnetic Resonance Spectroscopy , Metabolomics , Proton Magnetic Resonance Spectroscopy , SpleenABSTRACT
Longgu is the fossil of ancient mammals which was used as a common kind of mineral medicine. Longgu is always used to treat neurological diseases. Currently, the quality standard of Longgu is incomplete. Moreover, because of the non-renewable nature of the resource and the increase of national protection of fossils, the clinical application of Longgu is facing a series of problems. As the discovery of the ingredient and the development of forging technology researchers launched to search the substitutes of Longgu. The article summarizes the usage and the study of Longgu, in order that we can discuss the modern usage and substitutability of Longgu.
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To screen the anti-inflammatory active fraction of unripe Forsythiae Fructus, and elucidate the action mechanism, water decoction, ethyl acetate portion, n-butanol portion and residue water extracts of unripe Forsythiae Fructus were administered into rats for continuously 15 days. The acute lung injury inflammatory model was established to observe the section structure of lung tissues. Levels of IL-6, TNF-α, IL-1β and IL-10 in bronchoalveolar lavage fluid were determined by ELISA kits, and changes in endogenous metabolites in serum were analyzed based on 1H-NMR metabolomics. The results showed that ethyl acetate portion of unripe Forsythiae Fructus had a better anti-inflammatory activity against acute lung injury, and could suppress the release of inflammatory factors of IL-6, TNF-α, IL-1β, significantly reduce contents of creatine, β-OH-butyrate, succinate, lysine, valine, isoleucine and glutamine, and elevate the content of GPC in serum. Ethyl acetate portion was proved to be the main fraction of anti-inflammatory activity from the perspective of endogenous metabolites in serum, and played an anti-inflammatory role by regulating creatine metabolism, choline metabolism, branched-chain amino acid metabolism and TCA cycles. This study could lay a foundation for studying pharmacodynamic material basis of unripe Forsythiae Fructus.
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Thirteen compounds were isolated from the ethyl acetate fraction of Crepis crocea by column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. The structures were elucidated on the basis of spectral analysis as tectorone I (1), 8β- (2-methyl- 2-hydroxy-3-oxobutanoyloxy) -glucozaluzanin C (2), tectoroside (3), luteolin-7-O-glucoside (4), cosmosiin (5), esculetin (6), 3,4-dihydroxybenzaldehyde (7), trans-4-hydroxycinnamic acid (8), Caffeic acid (9), methyl p-hydroxyphenyllactate (10), ethylp- hydroxyphenyllactate (11), cis-3,4-dihydroxy-β-ionion (12). All the compounds, except for compounds 4 and 9, were isolated from this plant for the first time, and tectorone I (1) is a new natural product.
Subject(s)
Crepis , Chemistry , Drugs, Chinese Herbal , Chemistry , Mass Spectrometry , Molecular StructureABSTRACT
<p><b>OBJECTIVE</b>To establish a sensitive and specific HPLC fingerprint for the quality controlling of total flavonoids of Folium Apocyni Veneti.</p><p><b>METHOD</b>HPlC analysis was performed on a Kromasil C18 column (4.6 mm x 250 mm, 5 microm) with the mixture of solvent A [acetonitrile-phosphoric acid (95:5)] and solvent B (0.05% phosphoric acid) in gradient mode at a flow rate of 1.0 mL x min(-1). The detection wavelength was set at 360 nm. The column temperature was set at 25 degrees C and the injection volume was 20 microL.</p><p><b>RESULT</b>The chromatographic fingerprint of total flavonoids was established which showed 17 characteristic peaks from 7 patches of total flavonoids products. The similarity from different patches was 0.95-1.00 analyzed by the software of 'Computer-aided Similarity Evaluation' and showed high similitude in peak numbers and the retention time. Moreover, comparison of the HPLC profiles of the total flavonoids with the corresponding Folium Apocyni Veneti leaves indicated that they were closely related to each other.</p><p><b>CONCLUSION</b>The chromatographic fingerprint of the total flavonoids with high specificity and can be used to control its quality and assure the homogenicity for each patch of the total flavonoids.</p>