Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the interve...Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the intervention. Methods Methylation sites of genes were detected by the MeDIP-seq method. Bioinformatics method was used to analyze the gene methylation characteristics of obesity with phlegmdampness syndrome and the effect of Wen Dan Decoction. Results (1) There were 3 242 methylation differential loci in dietinduced obesity with phlegm-dampness syndrome, of which 1 243 were down-regulated and 1 999 were up-regulated, involving 1 579 differential genes. GO analysis showed that "offactory receptor activity" and others were enriched. The possible signal pathways involved were "Olfactory transduction""Tuberculosis""Systemic lupus erythematosus" and "Ribosome".(2) After the intervention of Wen Dan Decoction in obesity with phlegmdampness syndrome, 4 046 different methylation loci were obtained, including 1 067 down-regulated loci and 2 979 up-regulated loci, involving 2 068 genes. GO analysis showed that "offactory receptor activity" and others were enriched. These genes involved seven signaling pathways, such as "Metabolic pathways".(3) Between diet-induced obesity with phlegm-dampness syndrome and Wen Dan Decoction intervening obesity with the phlegm-dampness syndrome, 582 common genes of methylation differential genes were obtained. After the intervention of Wen Dan Decoction, the number of GO enrichment items was more than that of obesity with phlegm-dampness syndrome, and even the same GO enrichment items involved more genes. Conclusions The phlegm-dampness syndrome of obesityinduced by diet had the characteristics of gene methylation changes, and the intervention of Wen Dan Decoction could also affect the status of gene methylation. The genes affected by Wen Dan Decoction were closely related to the methylation gene of phlegm-dampness syndrome of obesity-induced by diet but covered a wider range.展开更多
AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: no...AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: normal control group (12), micro-amount carbon tetrachlodde group (CCh)(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCh in olive oil twice a week for 12 wk. The CCh group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (y-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis. RESULTS: A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCh group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P〈0.05). QGHXF high dose group was better than XCH group in ALT (615± 190 vs 867± 115),and AST(1972 ± 366 vs 2777 ± 608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4±3.13, 13.79±2.26 and 10.07± 1.14, higher than model group, 6.58±1.04 (P〈 0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group. CONCLUSION: QGHXF can improve liver fibrosis and induce HSC apoptosis.展开更多
Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets ...Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets of the TCM were retrieved using the systematic pharmacological analysis platform TCMSP,and the gene name of each target protein was obtained from the UniProtKB network platform.The targets of RA were queried through the CTD database.The protein–protein interaction network was constructed in the STRING database,and the network visualization analysis was performed in Cytoscape.The Gene Ontology and Kyoto Gene and Genomic Encyclopedia pathways enrichment analyses of key target proteins were performed using the DAVID data platform.Results:A total of 472 drug active ingredients were screened from the TCMSP database.Seventy-five disease targets from the CTD database were screened.The compound-target network map contained further screened out 98 components and corresponding 75 targets.The key compounds included quercetin and kaempferol.The key targets were prostaglandin G/H synthase 2 and nitric oxide synthase 2.The protein-protein interaction network consisted of 75 proteins,of which 37 were key proteins,including tumor protein 53,JUN and interleukin-6.There were 260 Gene Ontology entries,of which 246 were biological processes.Fifty-five Kyoto Gene and Genomic Encyclopedia pathways were enriched,mainly the cancer pathway,NOD-like receptor signaling pathway,and Toll-like receptor signaling pathway,which are involved in the action mechanism of FHD.Conclusion:The results of this study preliminarily verified the basic pharmacological action mechanism of FHD in the treatment of RA,laying a foundation for elucidating its mechanism of action.展开更多
OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by...OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by permanent ligation of the left anterior descending coronary artery. Echocardiography measurements were performed after the treatment of BYHWD(18 g·kg-1 collagen was observ·d-1) for 90 days.Myocardialed by mallory trichrome staining. Capillary density was quantified by using Factor rentially expⅧre immunohistochemical staining.Diffessed genes were explored by a short-read sequencing technology combined with a tag-based digital gene expression profiling(DGE)system. Real-time quantitative polymerase chain reaction detecting system(q PCR) was used to validate the sequencing results. After assembling the gene information from Sham, model and BYHWD groups, we constructed three DGE libraries based on each group. The sequencing of three libraries generated 66 000-73 000 unique tags, which were mapped to reference sequences for annotation of expressed genes.RESULTS: Among them, 511 and 352 differentially expressed genes were found in comparison with sham/model and model/BYHWD, respectively. Fifty-five genes exhibited reversed direction of gene expression differences between Sham/Model and Model/BYHWD groups. We found that transforming growth factor beta receptor-1, junctophilin-2,monocyte chemotactic protein 1, neuropeptide Y,arachidonate 5-Lipoxygenase, arachidonate 15-Lipoxygenase were significantly modulated, which suggested the involvement of these genes in BYHWD treatment.CONCLUSION: The DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the pharmacological mechanisms of BYHWD in ventricular remodeling post-myocardial infarction.展开更多
OBJECTIVE: To observe the therapeutic effect of Chishaodanpi decoction(CSDPD) on chronic viral cholestatic hepatitis.METHODS: A total of 107 subjects with chronic viral cholestatic hepatitis were enrolled in our hospi...OBJECTIVE: To observe the therapeutic effect of Chishaodanpi decoction(CSDPD) on chronic viral cholestatic hepatitis.METHODS: A total of 107 subjects with chronic viral cholestatic hepatitis were enrolled in our hospital from March 2007 to November 2012. Patients were randomly divided into treatment(54 cases)and control groups(53 cases). The control group was treated with potassium magnesium aspartate,diammonium glycyrrhizinate, glucurolactone, vitamin C, and lamivudine, once a day. The treatment group was treated with modified CSDPD, 100 m L a time, twice a day, in addition to the treatment given to the control group. The patients in both groups were treated for 8 weeks. The main symptoms and signs were recorded every day throughout the clinical trial. Before and after the trial,changes in liver function including total bilirubin(TBil), direct bilirubin(DBil), total bile acid(TBA),and the activities of alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), and γ-glutamyl transferase(γ-GT),were all detected. Adverse reactions were also recorded.RESULTS: There were no differences in gender, age,disease duration, symptoms, signs, or laboratory findings between the two groups(P>0.05). After an8-week treatment, improvements in jaundice, weakness, poor appetite, abdominal distention, and skin itching were significantly better in the treatment group than in the control group(P<0.05). In the treatment group, 43 patients had a significant response to the treatment, seven patients had a response, and four patients had no response, with 21,12, and 20 patients in the control group, respectively. The total effective rate was 92.6% in the treatment group and 62.3% in the control group, which was a significant difference(P<0.05). The levels of TBil, DBil, TBA, ALP, ALT, AST, and γ-GT in both groups were significantly lower after treatment,and were significantly different between the two groups(P<0.05). A few patients in the treatment group had mild adverse effects such as increased bowel movement frequency and mild stomachache. No other adverse reactions were observed in either group.CONCLUSION: CSDPD has a satisfactory therapeutic effect on chronic viral cholestatic hepatitis.展开更多
OBJECTIVE: To study metabolic characteristics of fever in rats induced by 2, 4-dinitrophenol (DNP) and the effect of Huanglianjiedu Tang (HLJDT) on the fever. METHODS: The urine samples were analyzed by ultra-performa...OBJECTIVE: To study metabolic characteristics of fever in rats induced by 2, 4-dinitrophenol (DNP) and the effect of Huanglianjiedu Tang (HLJDT) on the fever. METHODS: The urine samples were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) at the positive ion mode scanning, and experimental data were analyzed by the principal component analysis. RESULTS: Eight potential biomarkers indicating the occurrence and evolvement of fever were determined according to ions in urine samples. Five of them were found increased, while the other three decreased. After HLJDD intervention, the increased five were reduced significantly in high dose group, compared with model group, while the decreased three had no obvious change. Five of the eight biomakers were identified with formyl-5-hy-droxykynurenamine, gentisic acid, aminoadipic acid, phenylacetic acid, L-phenylalanyl-L-hydroxyproline on the basis of MS/MS.These biomarkers are associated with the metabolism of 5-hydroxytryptamine, tyrosine, lysine, phenylalanine and collagen protein, respectively. CONCLUSION: HLJDT had significant effect on DNP-induced fever in rats. The effect was performed possibly by acting on 5-hydroxytryptamine in hypothalamus and some amino acid metabolism. These results suggested that HLJDT relieved fever by acting on multi-targets.展开更多
基金the funding support from the National Natural Science Youth Foundation of China: Effect of Wen Dan Decoction on gene promoter methylations related to fat metabolism (No. 81302907)
文摘Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the intervention. Methods Methylation sites of genes were detected by the MeDIP-seq method. Bioinformatics method was used to analyze the gene methylation characteristics of obesity with phlegmdampness syndrome and the effect of Wen Dan Decoction. Results (1) There were 3 242 methylation differential loci in dietinduced obesity with phlegm-dampness syndrome, of which 1 243 were down-regulated and 1 999 were up-regulated, involving 1 579 differential genes. GO analysis showed that "offactory receptor activity" and others were enriched. The possible signal pathways involved were "Olfactory transduction""Tuberculosis""Systemic lupus erythematosus" and "Ribosome".(2) After the intervention of Wen Dan Decoction in obesity with phlegmdampness syndrome, 4 046 different methylation loci were obtained, including 1 067 down-regulated loci and 2 979 up-regulated loci, involving 2 068 genes. GO analysis showed that "offactory receptor activity" and others were enriched. These genes involved seven signaling pathways, such as "Metabolic pathways".(3) Between diet-induced obesity with phlegm-dampness syndrome and Wen Dan Decoction intervening obesity with the phlegm-dampness syndrome, 582 common genes of methylation differential genes were obtained. After the intervention of Wen Dan Decoction, the number of GO enrichment items was more than that of obesity with phlegm-dampness syndrome, and even the same GO enrichment items involved more genes. Conclusions The phlegm-dampness syndrome of obesityinduced by diet had the characteristics of gene methylation changes, and the intervention of Wen Dan Decoction could also affect the status of gene methylation. The genes affected by Wen Dan Decoction were closely related to the methylation gene of phlegm-dampness syndrome of obesity-induced by diet but covered a wider range.
基金Supported by Shanghai Rising-Star program, No. 03QMH1410
文摘AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: normal control group (12), micro-amount carbon tetrachlodde group (CCh)(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCh in olive oil twice a week for 12 wk. The CCh group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (y-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis. RESULTS: A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCh group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P〈0.05). QGHXF high dose group was better than XCH group in ALT (615± 190 vs 867± 115),and AST(1972 ± 366 vs 2777 ± 608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4±3.13, 13.79±2.26 and 10.07± 1.14, higher than model group, 6.58±1.04 (P〈 0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group. CONCLUSION: QGHXF can improve liver fibrosis and induce HSC apoptosis.
文摘Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets of the TCM were retrieved using the systematic pharmacological analysis platform TCMSP,and the gene name of each target protein was obtained from the UniProtKB network platform.The targets of RA were queried through the CTD database.The protein–protein interaction network was constructed in the STRING database,and the network visualization analysis was performed in Cytoscape.The Gene Ontology and Kyoto Gene and Genomic Encyclopedia pathways enrichment analyses of key target proteins were performed using the DAVID data platform.Results:A total of 472 drug active ingredients were screened from the TCMSP database.Seventy-five disease targets from the CTD database were screened.The compound-target network map contained further screened out 98 components and corresponding 75 targets.The key compounds included quercetin and kaempferol.The key targets were prostaglandin G/H synthase 2 and nitric oxide synthase 2.The protein-protein interaction network consisted of 75 proteins,of which 37 were key proteins,including tumor protein 53,JUN and interleukin-6.There were 260 Gene Ontology entries,of which 246 were biological processes.Fifty-five Kyoto Gene and Genomic Encyclopedia pathways were enriched,mainly the cancer pathway,NOD-like receptor signaling pathway,and Toll-like receptor signaling pathway,which are involved in the action mechanism of FHD.Conclusion:The results of this study preliminarily verified the basic pharmacological action mechanism of FHD in the treatment of RA,laying a foundation for elucidating its mechanism of action.
基金Supported by National Natural Science Foundation of China Project:Studies of Qi-Supplementing Therapy Promoting Angiogenesis after Myocardial Infarction by Simulation of Angptl6 Pathway in NK Cells(No.81302892)Effects of Polyamine-derived Aldehyde Load Injury in Long-term Prognosis after Myocardial Infarction Ventricular Remodeling,and the Modulation Mechanism of Buyanghuanwu Decoction(No.81173459)+4 种基金Studies of the Role of 5-LOX/Cys LT2R in Left Ventricular Remodeling after Myocardial Infarction and the Pharmacological Mechanisms of BYHWD(No.81373575)Effects of Hsp20 on Ventricular Remodeling after Myocardial Infarction,and the Modulation Mechanism of Buyanghuanwu decoction(No.81202841)Guangdong Natural Science Foundation Project:Studies of Qi-Supplementing Therapy Promoting Angiogenesis after Myocardial Infarction by Simulation of Angptl6 Pathway in NK Cells(No.S2013040016226)Studies of the role of 5-LOX/Cys LT2R in Left Ventricular Remodeling after Myocardial Infarction and the Pharmacological Mechanisms of BYHWD(No.S2013010014777)Specialized Research Fund for the Doctoral Program of Higher Education Project:Effects of Polyamine-derived Aldehyde Load Injury in Long-term Prognosis after Myocardial Infarction Ventricular Remodeling,and the Modulation Mechanism of Buyanghuanwu decoction(No.20124433110019)
文摘OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by permanent ligation of the left anterior descending coronary artery. Echocardiography measurements were performed after the treatment of BYHWD(18 g·kg-1 collagen was observ·d-1) for 90 days.Myocardialed by mallory trichrome staining. Capillary density was quantified by using Factor rentially expⅧre immunohistochemical staining.Diffessed genes were explored by a short-read sequencing technology combined with a tag-based digital gene expression profiling(DGE)system. Real-time quantitative polymerase chain reaction detecting system(q PCR) was used to validate the sequencing results. After assembling the gene information from Sham, model and BYHWD groups, we constructed three DGE libraries based on each group. The sequencing of three libraries generated 66 000-73 000 unique tags, which were mapped to reference sequences for annotation of expressed genes.RESULTS: Among them, 511 and 352 differentially expressed genes were found in comparison with sham/model and model/BYHWD, respectively. Fifty-five genes exhibited reversed direction of gene expression differences between Sham/Model and Model/BYHWD groups. We found that transforming growth factor beta receptor-1, junctophilin-2,monocyte chemotactic protein 1, neuropeptide Y,arachidonate 5-Lipoxygenase, arachidonate 15-Lipoxygenase were significantly modulated, which suggested the involvement of these genes in BYHWD treatment.CONCLUSION: The DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the pharmacological mechanisms of BYHWD in ventricular remodeling post-myocardial infarction.
文摘OBJECTIVE: To observe the therapeutic effect of Chishaodanpi decoction(CSDPD) on chronic viral cholestatic hepatitis.METHODS: A total of 107 subjects with chronic viral cholestatic hepatitis were enrolled in our hospital from March 2007 to November 2012. Patients were randomly divided into treatment(54 cases)and control groups(53 cases). The control group was treated with potassium magnesium aspartate,diammonium glycyrrhizinate, glucurolactone, vitamin C, and lamivudine, once a day. The treatment group was treated with modified CSDPD, 100 m L a time, twice a day, in addition to the treatment given to the control group. The patients in both groups were treated for 8 weeks. The main symptoms and signs were recorded every day throughout the clinical trial. Before and after the trial,changes in liver function including total bilirubin(TBil), direct bilirubin(DBil), total bile acid(TBA),and the activities of alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), and γ-glutamyl transferase(γ-GT),were all detected. Adverse reactions were also recorded.RESULTS: There were no differences in gender, age,disease duration, symptoms, signs, or laboratory findings between the two groups(P>0.05). After an8-week treatment, improvements in jaundice, weakness, poor appetite, abdominal distention, and skin itching were significantly better in the treatment group than in the control group(P<0.05). In the treatment group, 43 patients had a significant response to the treatment, seven patients had a response, and four patients had no response, with 21,12, and 20 patients in the control group, respectively. The total effective rate was 92.6% in the treatment group and 62.3% in the control group, which was a significant difference(P<0.05). The levels of TBil, DBil, TBA, ALP, ALT, AST, and γ-GT in both groups were significantly lower after treatment,and were significantly different between the two groups(P<0.05). A few patients in the treatment group had mild adverse effects such as increased bowel movement frequency and mild stomachache. No other adverse reactions were observed in either group.CONCLUSION: CSDPD has a satisfactory therapeutic effect on chronic viral cholestatic hepatitis.
基金Supported by the National Basic Research Program of China(No.2007CB512608)
文摘OBJECTIVE: To study metabolic characteristics of fever in rats induced by 2, 4-dinitrophenol (DNP) and the effect of Huanglianjiedu Tang (HLJDT) on the fever. METHODS: The urine samples were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) at the positive ion mode scanning, and experimental data were analyzed by the principal component analysis. RESULTS: Eight potential biomarkers indicating the occurrence and evolvement of fever were determined according to ions in urine samples. Five of them were found increased, while the other three decreased. After HLJDD intervention, the increased five were reduced significantly in high dose group, compared with model group, while the decreased three had no obvious change. Five of the eight biomakers were identified with formyl-5-hy-droxykynurenamine, gentisic acid, aminoadipic acid, phenylacetic acid, L-phenylalanyl-L-hydroxyproline on the basis of MS/MS.These biomarkers are associated with the metabolism of 5-hydroxytryptamine, tyrosine, lysine, phenylalanine and collagen protein, respectively. CONCLUSION: HLJDT had significant effect on DNP-induced fever in rats. The effect was performed possibly by acting on 5-hydroxytryptamine in hypothalamus and some amino acid metabolism. These results suggested that HLJDT relieved fever by acting on multi-targets.