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To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.
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Drugs, Chinese Herbal/pharmacology , Network Pharmacology , Molecular Docking Simulation , RhizomeABSTRACT
The pathological changes of the heart after myocardial infarction （MI） are complex， involving multiple molecular mechanisms and various cells， such as myocardial cells， endothelial cells， fibroblasts， and macrophages. With multiple targets， Chinese medicine demonstrates ideal cardioprotective effect. However， the complex mechanism of multi-component Chinese medicine formulas has not been elucidated， thus limiting the further application. The high-throughput single-cell RNA sequencing （scRNA-seq） technology offers single-cell transcriptome analysis of hundreds of drugs under different processing conditions in a single experiment and identifies the differences in the response of different cells and cell subtypes to drug treatment. scRNA-seq technology helps us to understand the exact cellular and molecular mechanisms of cardiac remodeling from acute ischemic events to chronic cardiac scarring. The application of scRNA-seq to studying the cardioprotective mechanism of Chinese medicine after MI can boost the development of Chinese medicine， help obtain richer， more accurate and comprehensive information. It can give us a clear insight into the mechanism of Chinese medicine based on complex network. In this study， we summarized the research on cardioprotective mechanism of Chinese medicine and introduced the development of scRNA-seq technology and the application to MI research. Finally， we explored the possible application prospects of scRNA-seq in the research on cardioprotective mechanism of Chinese medicine after MI， hoping to provide ideas for the modernization of Chinese medicine.
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Objective:To study the extraction method and characteristics of vesicle-like nanoparticles （VLNs） in Astragali Radix decoction， and to explore the mechanism of the VLNs in reducing blood glucose by regulating the gut microbiota of db/db diabetic mice. Method:Ultracentrifugation and size exclusion chromatography were used to enrich VLNs from Astragali Radix decoction， and the morphology， particle size and concentration of the VLNs were analyzed by transmission electron microscope and nanoparticle tracking analyzer. The db/db diabetic mice were randomly divided into model group， Astragali Radix VLNs high-， medium- and low-dose （21.1， 10.6， 5.3 g·kg<sup>-1</sup>） groups and metformin group （0.25 g·kg<sup>-1</sup>） according to their blood glucose levels. There were 7 mice in each group， and another 7 C57BL/6 mice were set as the normal group. The mice were given intragastrically for 3 weeks （once a day）， and the changes of fasting blood glucose were observed every week. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of liver and pancreas of diabetic mice. The feces of mice were collected for 16S rRNA diversity detection of intestinal microbes. Result:The size of the nanoparticles obtained by the two methods was about 200 nm. Astragali Radix VLNs extracted by ultracentrifugation had a typical saucer-like shape with the concentration of 3.0×10<sup>11</sup> particles·mL<sup>-1</sup>. The morphology of Astragali Radix VLNs obtained by size exclusion chromatography was relatively poor with the concentration of 2.2×10<sup>11</sup> particles·mL<sup>-1</sup>. After 3 weeks of administration， compared with the model group， Astragali Radix VLNs high-， medium- and low-dose groups could significantly reduce the fasting blood glucose of diabetic mice （<italic>P</italic><0.05， <italic>P</italic><0.01）. The VLNs could improve the gut microbiota dysbiosis， significantly decrease the ratio of Firmicutes/Bacteroidota， and increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. Conclusion:Astragali Radix VLNs may reduce the blood glucose of db/db diabetic mice by adjusting the ratio of Firmicutes/Bacteroidota in the intestinal flora.
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Objective:To explore the molecular mechanism of Jiangtang Xiaozhi tablets （JTXZT） in the treatment of non-alcoholic fatty liver disease （NAFLD） by means of network pharmacology and molecular docking. Method:With the help of traditional Chinese medicine （TCM） Systems Pharmacology Database and Analysis Platform （TCMSP）， TCMs Integrated Database （TCMID）， Encyclopedia of TCM （ETCM） and Bioinformatics Analysis Tool for Molecular Mechanism of TCM （BATMAN-TCM）， the chemical compositions of medicinal materials in JTXZT were obtained， the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database （GeneCards）， Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD） and DisGeNET， and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database， the protein-protein interaction （PPI） network of therapeutic targets was constructed， and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally， the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking. Result:The key components of JTXZT for treatment of NAFLD were quercetin， luteolin， kaempferol， berberine， isorhamnetin， betulinic acid， oleanolic acid， ursolic acid. formononetin and hexitol， and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 （MAPK1）， Jun proto-oncogene， activator protein-1 （AP-1） transcription factor subunit （JUN）， MAPK3， protein kinase B1 （AKT1 or Akt1）， tumor protein p53 （TP53）， E1A binding protein p300 （EP300）， Fos proto-oncogene， AP-1 transcription factor subunit （FOS）， tumor necrosis factor （TNF），amyloid beta precursor protein （APP） and cytochrome P450 family 2 subfamily E member 1 （CYP2E1）. Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process， oxidation-reduction process， cholesterol metabolic process and other biological processes， regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， MAPK signaling pathway， NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD. Conclusion:JTXZT treats NAFLD through multiple active components， multiple key targets and multiple action pathways.
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Cerebral ischemia can induce weak endogenous neurogenesis, which is not enough to repair neural injury after cerebral ischemia.In the treatment of cerebral ischemic diseases with Chinese medicine, different treatment methods based on syndrome differentiation are adopted according to the pathological mechanism of the diseases, and the advantages of neural repair after cerebral ischemia are well shown through comprehen-sive regulation.And in this paper, the effects of inflammation, neurovascular units, exogenous stem cell transplantation, exo- somes and other factors on neurogenesis and repair after cerebral ischemia and the intervention of Chinese medicine are described.
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Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.
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Animals , Rats , Heart Failure/drug therapy , Medicine, Chinese Traditional , Panax , Proteomics , Qi , Rats, Sprague-DawleyABSTRACT
The pharmacology of Chinese medicine is an academic discipline that studies the interaction between Chinese medicine and organism(including pathogens) by modern science and technology under the guidance of traditional Chinese medicine(TCM) theories. However, the pharmacology of Chinese medicine is mainly guided by the theories, techniques, and methods of modern medicine in the development, and TCM theories have been ignored to a certain extent, which does not conform to the action characteristics of Chinese medicine in essence. Since systematic research ideas, strategies, methods, and technologies that conform to the characteristics of TCM have not been established, it is unable to reveal the scientific connotation of TCM in the prevention and treatment of diseases. Therefore, according to the trend of the modern development of TCM and the research status of pharmacology of Chinese medicine, this study put forward the concept of pharmacology of combination of disease and syndrome and expounded the relevant background, content, methods, and significance of this concept. It is expected to improve the standardization of pharmacology of combination of disease and syndrome, guide the safe medication, provide new references for the scientific development of pharmacology of Chinese medicine, and promote the development of the modernization of Chinese medicine.
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Humans , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Social Change , SyndromeABSTRACT
Single-cell transcriptome sequencing(scRNA-seq) can be used to analyze the expression characteristics of the transcriptome at the level of individual cell, and discover the heterogeneity of gene expression in individual cell that is "diluted" or averaged in study of group organization. The scRNA-seq, with the characteristics of standardization, high-throughput, and high integration, can greatly simplify the experimental operation and significantly reduce the consumption of reagents. At the same time, a variety of cells are screened and the gene expression patterns are analyzed at the single-cell level to provide a more efficient detection technique and more rich and accurate information for drug research. In the field of traditional Chinese medicine(TCM), the scRNA-seq is still a new technology, but the individual and precision concepts embodied by scRNA-seq and the theory of TCM syndrome differentiation and treatment have reached the same effect between the micro and macro aspects. This study tried to broaden the thinking for the modernization of TCM by introducing the development of scRNA-seq technology and its application in modern drug research and discussing the application prospects of scRNA-seq in TCM research.
Subject(s)
Gene Expression Profiling , Medicine, Chinese Traditional , Reference Standards , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
Objective:To investigate the medication rules of traditional Chinese medicine (TCM) for the treatment of diabetic peripheral neuropathy (DPN).Method:The literature published in China Knowledge Resource Integrated Database (CNKI), Wanfang Database, China Biomedical Literature Service System (SinoMed), VIP Database and PubMeb from 2008 to 2019 were retrieved by setting the topics of diabetic peripheral neuropathy and TCM. After screening, a database was established to analyze the medication rules (efficacy, frequency, flavor and meridian tropism, common couplet medicinals and core medicines) of TCM by frequency statistics, association rules and data statistical methods of constructing complex networks.Result:A total of 461 papers for treatment of DPN were included in this study, including 275 kinds of TCM and a total frequency of 6 361 times. Astragali Radix had the highest frequency. Among all kinds of medicinal materials, activating blood circulation and removing stasis was the most commonly used medicine, followed by Qi-invigorating medicine. Flavor of medicines was mainly sugariness and warm, and most of their meridian tropism was liver meridian. After the analysis by association rules, the couplet medicinals with the highest support was Astragali Radix-Angelicae Sinensis Radix. The core medicines obtained by complex network analysis were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Spatholobi Caulis, Cinnamomi Ramulus, Carthami Flos, Pheretima, Paeoniae Radix Rubra, Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen.Conclusion:This study comprehensively analyzes the medication rules of TCM clinical treatment of DPN. The main treatment methods of TCM for DPN are invigorating Qi and blood, activating blood circulation and removing stasis, activating meridians to stop pain, which can provide guidance for the TCM clinical use and new Chinese medicines research and development of DPN.
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Objective:To investigate the therapeutic effect of Qihong capsule on pentobarbital sodium induced heart failure in beagle dogs. Method:Thirty healthy adult beagle dogs were randomly divided into 6 groups, 6 in each group. They were normal group, model group, digoxin tablet group (40 μg·kg-1), Qihong capsule high, medium and low dose groups (2.6，1.3，0.65 g·kg-1). The heart failure model of beagle dogs was established by intravenous infusion of 2% pentobarbital sodium. The success standard of the model was that the maximum rate of rise of left ventricular pressure was reduced by 70%.The corresponding drugs were given through duodenum. The Ⅱ lead electrocardiogram, coronary blood flow, cardiac output, left ventricular pressure and maximum rate of left ventricular pressure rise were measured by multi-channel physiological recorder. The arterial oxygen content and coronary sinus oxygen content were measured by Roche blood oxygen analyzer at different time points, and the myocardial oxygen utilization rate was calculated. Result:After intravenous infusion of 2% pentobarbital sodium for about 15 minutes, beagle dogs began to show obvious symptoms of heart failure. The main manifestations were the increase of PR interval of Ⅱ lead electrocardiogram, the decrease of coronary blood flow, left ventricular pressure, cardiac output, cardiac output, venous oxygen content, and the increase of myocardial oxygen utilization rate (P<0.01) compared with the model group, Qihong capsule significantly increased coronary blood flow at 60-120 min after treatment (P<0.05). The cardiac output of 2.6 g·kg-1 Qihong capsule increased significantly at 45-60 min after treatment, with the maximum increase of about 16%, which was significantly different from that of model group (P<0.05). At the same time, it can increase the oxygen content of coronary sinus blood, which indicates that the myocardial oxygen supply is increased and the oxygen utilization rate is decreased. Qihong capsule 1.3 g·kg-1 group significantly increased the maximum rate of left ventricular pressure rise (P<0.05), the maximum increase rate was about 42%. Conclusion:Qihong capsule can increase coronary blood flow and venous blood oxygen content at the same time, make myocardial nutrient supply sufficient, reduce oxygen utilization rate, on this basis, Qihong capsule can further increase cardiac output and improve cardiac function, so as to play a protective role in heart failure.
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Objective:To explore the mechanism of Qizhu granules in the treatment of diabetic nephropathy by using network pharmacology. Method:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database （TCMSP） and The Encyclopedia of Traditional Chinese Medicine（ETCM） database were used to screen out the chemical constituents and protein targets of each drug in the Qizhu granules based on oral bioavailability and drug-like properties. The protein target was standardized into the corresponding gene name through the UniProt database. Online Mendelian Inheritance in Man（OMIM）， DisGeNET， Therapeutic Target Database （TTD）， ETCM database were used to search for related targets of diabetic nephropathy， after the intersection of the two， construct a protein interaction network through protein interaction database （STRING）， use Cytoscape to analyze the core target of the network， and the relevant targets were analyzed by KOBAS 3.0 database for Gene Ontology （GO） pathway enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Result:A total of 93 chemical components were obtained from Qizhu granules， involving 254 targets， and 607 targets related to diabetic nephropathy. After the intersection， 76 sputum granules were determined to treat diabetic nephropathy， including protein kinase B1 （Akt1）， vascular endothelial growth factor （VEGFA）， interleukin （IL）-6， tumor necrosis factor （TNF）， mitogen-activated protein kinase 1 （MAPK1）， matrix metalloproteinase （MMP）-9 and other core targets， after GO analysis and KEGG analysis， Qizhu granules can affect cellular response to nitrogen compound， regulation of reactive oxygen species metabolic process and other biological processes， regulate advanced glycation end product （AGE）/advanced glycation end product receptor （RAGE） signaling pathway in diabetic complications， fluid shear stress and atherosclerosis， IL-17 signaling pathways， HIF-1 signaling pathways TNF signaling pathways and other pathways. Conclusion:The therapeutic effect of Qizhu granules on diabetic nephropathy may affect Akt1，VEGFA， IL-6， TNF， MAPK1， MMP-9 and other targets， and regulate AGE/RAGE signaling pathway in diabetic complications， fluid shear stress and atherosclerosis， IL-17 signaling pathways， hypoxia-inducing factor-1（HIF-1）signaling pathways TNF signaling pathways and other pathways， which can provide a theoretical reference for further basic experimental research.
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Cerebral ischemia is also known as ischemic stroke. In recent years, research on neuroprotection after ischemia has became a hot spot as stroke can result in symptoms of nerve damages such as hemiplegia, learning and memory disorders. The key factors that cause the death of cells include excitotoxicity, oxidative damage, nitrosative stress and inflammation. However, there is no effective preparation for the treatment of post-ischemic nerve defects at present, so it is urgent to find and develop effective drugs for the treatment of nerve damages after ischemia. Traditional Chinese medicine has advantages and potentials in the treatment of neurological diseases. Many scholars have carried out related researches on the active ingredients of traditional Chinese medicine and achieved some good results. In this context, the researches on the neuroprotective effects of traditional Chinese medicines such as tetramethylpyrazine, butylphthalide and total saponins of Panax notoginseng were reviewed. The author found that the neuroprotective researches of traditional Chinese medicine mostly focused on anti-apoptosis, anti-inflammatory and anti-oxidative stress, but those effects were not sounique to the nervous system. Furthermore, most ingredients of traditional Chinese medicine showed a poor water-soluble property. In view of the research status and existing problems of traditional Chinese medicine in nerve injury, the suggestions for the research and development of the potent neuroprotective agents were proposed in this study from the perspective of pharmacological mechanism research and preparation theory.
Subject(s)
Humans , Benzofurans/therapeutic use , Brain Ischemia/drug therapy , Cerebral Infarction/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Neuroprotective Agents/therapeutic use , Panax notoginseng , Pyrazines/therapeutic use , Saponins/therapeutic useABSTRACT
Objective: To explore the changes and benefits of vascular endothelial cell function in rats with qi deficiency and blood stasis syndrome, and the effect of Yiqi Huoxue recipe (YQHXF) of such changes. Method: Rats were randomly divided into blank control group, Qi deficiency and blood stasis group, and YQHXF high and low dose groups (5.54,2.77 g·kg-1). A small platform of water environment was used to make the rats stand for a long-term with irregular and incomplete sleep deprivation, 16 h per day for six weeks, so that both mentality and labor of rats were consumed to establish qi deficiency and blood stasis rat models. From the fifth week, intragastric administration was given for 2 weeks, until end of the experiment. Then levels of endothelin-1(ET-1), von willebrand factor (vWF), vascular cell adhesion molecule-1(VCAM-1), intercellular adhesion molecule (ICAM-1), P-selectin,interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in rat plasma were detected by enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) was detected by nitrate reductase assay. Result:Compared with blank control group, rats in Qi deficiency and blood stasis group showed rough and dark hair, with significantly decreased body weight and pulse amplitude (PPPα were abnormally increased after sleep deprivation (PPPPPPPConclusion:Sleep deprivation can induce the formation of Qi deficiency and blood stasis syndrome in rats, and lead to vascular endothelial dysfunction. YQHXF has the function of protecting the vascular endothelium. It can improve the Qi deficiency and blood stasis symptoms in rats with Qi deficiency and blood stasis syndrome by regulating the secretion of vascular endothelial active substances, reducing cell adhesion and inhibiting inflammation.
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Objective: To investigate the effect and mechanism of cinnamaldehyde on the angiogenesis of diabetic retinopathy, and the effect of cinnamaldehyde on vascular endothelial growth factor (VEGF) induced proliferation, migration, tube formation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway of EA.hy 926 cells were observed. Method:EA.hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (60, 90, 120, 150 μmol·L-1). The methyl thiazolyl tetrazolium (MTT) assay and scratch test were used to observe the effect of cinnamaldehyde on the proliferation and migration of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (90, 150 μmol·L-1). The tube formation experiment was used to observe the effect of cinnamaldehyde on the tube formation of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), VEGF+AG490 group (50 μmol·L-1), VEGF+cinnamaldehyde group (90 μmol·L-1), VEGF+cinnamaldehyde group (150 μmol·L-1), and VEGF+cinnamaldehyde group (150 μmol·L-1)+AG490 group (50 μmol·L-1). Western Blot method was used to explore the effect of cinnamaldehyde on the JAK2/STAT3 signaling pathway in EA.hy 926 cells induced by VEGF. Result:Compared with the control group, model group obviously promoted the proliferation and migration of EA.hy 926 cells(P-1) significantly suppressed VEGF-induced proliferation and migration of EA.hy 926 cells (P-1) showed an obvious inhibitory effect on the number of nodes, junctions and meshes of tubules (PPPP-1) significantly reduced the expressions of P-JAK2, P-STAT3, STAT3 proteins (P-1) obviously reduced the expressions of p-STAT3 and STAT3 proteins (PPConclusion:Cinnamaldehyde showed a significantly inhibitory effect on the proliferation, migration and tube formation of VEGF-induced EA.hy 926 cells, which was related to the inhibition of the activation of JAK2/STAT3 pathway.
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The comparison on evaluating blood stasis syndrome in sleep deprived rats was carried out by using R, G, B image analysis of Tongue and palm as well as auricle, palm surface laser Doppler flow perfusion. The experiment was performed by means of a small platform on the water environment for sleep deprivation. The rats were weekly weighed at fixed time, and their macroscopic signs were observed; and their tongue and palm images of the control and model group were respectively collected by the SLR camera at the 2nd, 4th and 6th week. Then the color saturation analysis was performed by means of proofreading with the standard colorimetric card. At the same time, the laser dopper flowmetry was used to analyze the perfusion of auricle and foot flow in rats. It turned out that there was no significant difference in the R,G,B value of the tongue and palm in rats between normal group and model group at the first stage(at the 2nd week), so were the perfusion of auricle and foot flow in rats. But at the second stage (at the 4th week), the R value of tongue in model group rats was obviously lower than that in normal group(<0.01), and the other value (G,B) of tongue in module rats had a decease tendency, but there was no statistical significance. However, the perfusion of left and right auricle flow in model group rats were dramatically decreased as compared with the normal group(<0.01); there was still no significant difference in the perfusion of the palm between two groups. It was found that R,G,B value in model group had a lower trend as compared with the control group of the tongue and palm images at the third stage (at the 6th week), but no statistically significant difference. The perfusion of left and right auricle flow in model group was constantly decreased as compared with the normal group(<0.01).Right and left foot blood flow was lower than the normal group, but no statistically significant difference. We can safely conclude that the results of the R, G, B values of the tongue in rats could objectively reflect the characteristics of the rats with blood stasis syndrome, which were consistent with the diagnosis of clinical tongue image. As a method of microcirculation evaluation, the surface laser doppler perfusion of auricle can exhibit the characteristics of blood stasis in model rats, but also was more objective and reproducible. Therefore, the combination of R, G, B value of tongue as well as auricle laser doppler blood flow is more beneficial to the objective evaluation of index in the later study of traditional Chinese medicine blood stasis syndrome model.
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Based on the theory of "overexertion leading to Qi consumption", this study aimed to compare the intervention factors of nervous and physical fatigue to establish a rat model of Qi deficiency syndrome, moreover, the systematic evaluationsystem was necessary with the standard of syndrome diagnosis of Qi deficiency. According to the clinical-mimetic principle the Qi deficiency syndrome animal model is established by the factors of sleep deprivation(SD) and exhaustive swimming(ES). Rats were randomly divided into four groups, normal group, SD group, ES group and compound group (exhaustion swimming complex sleep deprivation). The method of ES was force rats to swim until the exhaustion with 5% of weight, and the SD method by using multi-platform sleep deprivation of water environment randomly 14-16 h daily, and the complex set by using of two methods was combined. The movement distance, average speed, activity time and numbers into the central area were detected by open field test, swimming exhaustion time was detected by swimming exhaustion method, the cardiac function (LVEF, CO, FS, LVDd) was detected by echocardiography, tongue imaging analysis and pulsedistention as the index of tongue and pulse diagnosis, the content of ATP and ADP in serum was detected by ELISA, the blood coagulation indexes for blood stasis syndrome as the additional. These results indicated that independent activity, body weight and exercise capacity were decreased significantly, the neurological function injured significantly, heart function was decreased significantly, the tongue surface color was pale white, and the pulse distention was decreased significantly. The content of ATP decreased significantly and the ADP increased significantly. By the method of four-diagnostic evaluation system to compare the factors of SD and ES, the Qi deficiency syndrome animalmodel could be successfully established by sleep deprivation method.
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As a basic syndrome of Chinese medicine, the study of characteristic syndrome spectrum of Qi deficiency syndrome is of great significance for the standardization of clinical diagnosis and modern material basis research. Suitable operators and algorithms were chosen to dig out the relationship between diseases, syndromes, symptoms, detection indicators and etiologist from the literature of Chinese clinical and basic research by literature mining method of frequency statistics, association rules and complex network analysis. Moreover, the information system of Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences was taken as the tools of data mining. The objective was to study the characteristic spectrum of Qi deficiency syndrome and to explore the characteristics of Qi deficiency syndrome. The results showed that the syndrome of fatigue, dietary were the main factors. The main pathogenesis of coronary heart disease, heart failure, chronic obstructive pulmonary disease, diabetes and stroke the disease were Qi deficiency. The clinical features of Qi deficiency syndrome were fatigue, shortness of breath and pale tongue. The biological indicators of Qi deficiency related were blood lipids, ECG, blood rheology, inflammatory reaction, NO, ET and NF-κB signalling pathway. The Qi deficiency syndrome on the level of syndrome spectrum was studied by the method of literature mining, which would provide reliable characteristic guidance data for the research on the substantial basis of Qi deficiency, the research on standard of diagnosis, establishment of syndrome model, the study on combination of disease and syndrome and the mechanism of prescriptions.
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Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but the pharmacological basis is still not clear. This study aims to uncover the biological basis of BYHW therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome using label-free proteomic technology. Using Qi deficiency and blood stasis rat cerebral infarction model as the research object, the protein expression of rat brain tissue was compared among the sham operation group, the model group and the drug group. Quantitative analysis of the 3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham operation group, the model group and the drug group, respectively. Take model group as the control group, 391 proteins were identified to be upregulated or downregulated for more than 2 folds. Biological analysis and functional enrichment of the differentially expressed proteins revealed that BYHW may treat cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through energy metabolism, nervous system and several signal pathways. This study preliminarily revealed the pharmacological mechanism of BYHW at the protein level, and provided a molecular basis for clinical treatment and traditional Chinese medicine research on cerebral infarction combined with Qi-deficiency and blood-stasis syndrome.
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Blood stasis syndrome is the pre-state of thrombotic disease. The model of blood stasis syndrome in rats was induced by sleep deprivation to study on effects of blood stasis syndrome on platelet activation. The weight, the color of tongue and hemorheology for the blood stasis syndrome of Chinese medicine were measured after modeling. The release of platelet granules and platelet activation factors in plasma were detected by ELISA kit related indicators to provide experimental basis for platelet function evaluation and related drug effects in syndrome research. The results showed that the weight of the model group rats was significantly lower than that of the normal group (<0.01). The tongue showed a dark purple blood stasis pattern, and the R, G and B values of the tongue surface in model group were significantly lower than those of the normal group (<0.01). The hemorheological parameters including high shear, middle shear and low shear viscosity in whole blood were significantly higher than those in the normal group (<0.01). But plasma viscosity did not change significantly. The release levels of platelet α particles (GMP-140, -TG, PF4) and dense particles (ADP, 5-HT) were significantly higher than those in the normal group (<0.01). The levels of TXB₂ and 6-keto-PGF₁α in plasma were significantly higher than those in the normal group (<0.01). The ratios of TXB₂ and 6-keto-PGF₂α were also significantly higher than those in the normal group (<0.01). The levels of PAF in plasma in model group were significantly higher than those in the normal group (<0.01). It was concluded that platelet functions could be changed induced by sleep deprivationin rats with blood stasis syndrome, and there might be inflammation and endothelial cell dysfunction.
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To find the relationship between traditional efficacy of Chinese medicine and modern pharmacological action by using data mining, and provide information and reference for further research and development for the pharmacology research of traditional Chinese medicine.The information of 547 kinds of traditional Chinese medicines, 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions were collected and processed in Clinical Guide to the Chinese Pharmacopoeia published in 2010; Access and Excel software were used to analyze the frequence and frequency of single effect, pharmacological action, and both. In addition, the relationship between efficacy and pharmacology was analyzed with the clearing heat and antibacterial effects as the example. The analysis results showed that 547 kinds of Chinese medicines involved 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions. Among them, the most frequent Chinese medicine effect was"clearing heat", whose frequence was 130 and the frequency was 0.24; the most frequent pharmacological action was "anti-inflammatory action" whose frequence was 191 and the frequency was 0.35. The most common efficacy-pharmacological action group was "clearing heat" and "anti-bacterial action", whose frequence was 75 and the frequency was 0.26. The couple of "purgation" and "cathartic effect" had the largest frequency of 0.30, but they just appeared together for 3 times. There were 52 kinds of pharmacological actions that occurred together with clearing heat, of which, the top 10 were anti-bacterial action, anti-inflammatory action, antineoplastic action, anti-hepatic injury action, immunoregulation action, antipyretic action, antiviralaction, hypoglycemic action, antioxidant action and analgesic action. There were 161 kinds of Chinese medicine effects that occurred together with anti-bacterial action, of which, the top 10 were clearing heat, detoxification, detumescence, analgesia, resolving dampness, pesticide, cooling blood, expelling wind, eliminating dampness and hemostasis. These results suggested that there was a certain relationship between traditional Chinese medicine effects and modern pharmacological actions.