BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedent...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.展开更多
BACKGROUND To analyze the potential action mechanism of Huangqin decoction(HQD)in colorectal cancer(CRC)treatment on the basis of network pharmacology and molecular docking.AIM To investigate the molecular mechanisms ...BACKGROUND To analyze the potential action mechanism of Huangqin decoction(HQD)in colorectal cancer(CRC)treatment on the basis of network pharmacology and molecular docking.AIM To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking.METHODS All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine.Then,the targets of the active ingredients were screened.The abbreviations of protein targets were obtained from the UniProt database.A“drug–compound–target”network was constructed to screen for some main active ingredients.Some targets related to the therapeutic effect of CRC were obtained from the GeneCards,DisGeNET,Therapeutic Target Database,and Online Mendelian Inheritance in Man databases.The intersection of targets of Chinese herbs and CRC was taken.A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database.Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC.The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization.Finally,molecular docking was performed using AutoDockTool and PyMOL for validation.RESULTS In total,280 potential drug-active ingredients were present in HQD,including 1474 targets of the drug-active ingredients.The main active ingredients identified were betulin,tetrahydropalmatine,and quercetin.In total,10249 CRC-related targets and 1014 drug-disease intersecting targets were identified,including 28 core targets of action such as Jun proto-oncogene,AP-1 transcription factor subunit,signal transducer and activator of transcription 3,tumor protein p53,vascular endothelial growth factor,and AKT serine/threonine kinase 1.The gene ontology enrichment functional analysis yielded 503 enrichment results,including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia,etc.In total,38 cellular components were primarily related to polymer complexes,transcription factor complexes,and platelet alpha granule lumen.Then,59 molecular functions were closely related to the binding of enzymes,homologous proteins,and transcription factors.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results,involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways.CONCLUSION HQD can play a role in CRC treatment through the“multi-component-target–pathway”.The active ingredients betulin,tetrahydropalmatine,and quercetin may act on targets such as Jun proto-oncogene,AP-1 transcription factor subunit,signal transducer and activator of transcription 3,tumor protein p53,vascular endothelial growth factor,and AKT serine/threonine kinase 1,which in turn regulate HIF-1 and mitogen-activated protein kinase signaling pathways in CRC treatment.The molecular docking junction clarified that all four key target proteins could bind strongly to the main HQD active ingredients.This indicates that HQD could slow down CRC progression by modulating multiple targets and signaling pathways.展开更多
Background:Through the use of network pharmacology and molecular docking approaches,this study will examine the pharmacological effects of Sanwu Huangqin Tang on restless legs syndrome in order to better understand th...Background:Through the use of network pharmacology and molecular docking approaches,this study will examine the pharmacological effects of Sanwu Huangqin Tang on restless legs syndrome in order to better understand the mechanism of action of Traditional Chinese medicine(TCM)on RLS.Method:Utilise the TCMSP database to collect and select the drug components of Sanwu Huangqin Tang,and the Uniprot database to identify pertinent targets;RLS-related disease targets were obtained from GeneCards,DrugBank,and OMIM databases;and STRING and Cytoscape 3.9.1 software were used to generate an interaction network.KEGG pathway analysis and GO enrichment analysis were performed utilizing the DAVID database.Use Autodock for analyzing the relationships between targets and core components.Result:By using a network pharmacology approach,83 active ingredients and 50 drug-disease intersecting targets were derived for Sanwu Huangqin Tang.The molecular docking results showed that the drug components had strong affinity with the average target targets.Conclusions:This study provides new insights into the mechanism through which Traditional Chinese Medicine(TCM)treats Restless Legs Syndrome(RLS).Furthermore,it lays the foundation for additional research into the mechanism of treatment for RLS through the intervention that addresses various targets and pathways using the active ingredients identified by Sanwu Huangqin Tang.展开更多
Objective:To analyze the main compounds of Sanwu Huangqin decoction based on the method of network pharmacology and to predict its possible target and mechanism of action in the treatment of Behcet's disease(BD).M...Objective:To analyze the main compounds of Sanwu Huangqin decoction based on the method of network pharmacology and to predict its possible target and mechanism of action in the treatment of Behcet's disease(BD).Methods:TCMSP,TCMID and literatures were used to search the main compounds and their corresponding targets of Sanwu Huangqin Decoction;the disease targets of BD were searched by GeneCards database;the intersection targets of Sanwu Huangqin Decoction and BD were visualized by String database and Cytoscape software;the intersection targets were enriched by GO and KEGG by DAVID database;BD mouse model was established,RT-PCR was used to verify the regulatory effect of Sanwu Huangqin Decoction on the core target genes.Results:A total of 81 main active compounds and 50 drug-disease-target were retrieved from the databases.There were 531 biological function information and 96 signal pathways were enriched by GO and KEGG.Among them,the top 5 signal pathways were Fluid shear stress and atherosclerosis、AGE-RAGE signaling pathway in diabetic complications、IL-17 signaling pathway、TNF signaling pathway、Malaria、Chagas disease(American trypanosomiasis).RT-PCR results showed that the expression of IL-4,IL-1β,IL-6,INF-γmRNA in the spleen of BD mice was significantly up-regulated,and the expression of Caspase 3 and Caspase 8 mRNA was significantly down regulated when compared with the control group(P<0.01).Compared with the model group,the expression of IL-4,IL-1β,IL-6,INF-γmRNA in the Sanwu Huangqin decoction group was significantly down regulated,and the expression of caspase 3 and caspase 8 mRNA was significantly up regulated(P<0.01).Conclusion:Sanwu Huangqin decoction can treat BD through multi-target and multi-channel therapy,and our study and our research provides bioinformatics basis for further revealing its mechanism and treatment.展开更多
Objective:To investigate the effect of Sanwu Huangqin Decoction on IFN-γand IL-17A levels in mice with Behcet's disease;Methods:Clinical samples of patients with Behcet's disease were collected and mononuclea...Objective:To investigate the effect of Sanwu Huangqin Decoction on IFN-γand IL-17A levels in mice with Behcet's disease;Methods:Clinical samples of patients with Behcet's disease were collected and mononuclear cells were isolated.High throughput RNA-seq was used to identify the different genes between Behcet's disease and healthy subjects.Mouse model was constructed by shrimp myosin sensitization and treated with Sanwu Huangqin decoction.The levels of IFN-γand IL-17A in peripheral blood and mononuclear cells were detected by ELISA and flow cytometry.The expression level of TBX21 gene in spleen was detected by RT-PCR;Results:Compared with healthy subjects,31 differential genes were identified in BD patients,of which 19 genes were up-regulated and 12 genes were down regulated.PPI analysis showed that the top 5 genes were TBX21,STAT3,IL15,PRF1 and IFNG.The results of animal experiments showed that the levels of IFN-γand IL-17A in the peripheral blood and PBMC of the model group were significantly higher compared with the control group(P<0.01).Sanwu Huangqin decoction could significantly reduce the levels of IFN-γand IL-17A in the peripheral blood and PBMC of mice(P<0.05 or P<0.01).RT-PCR results showed that the expression of TBX21 mRNA in spleen tissue of model group was significantly higher than that of the control group(P<0.01).Sanwu Huangqin decoction could significantly down-regulate the expression of TBX21 mRNA in spleen(P<0.05 or P<0.01);Conclusion:Sanwu Huangqin decoction reduce the levels of IFN-γand IL-17A by inhibiting the expression of TBX21 mRNA,so as to achieve the effect of treating BD.展开更多
Objective:To find out the potential mechanisms of Huangqin decoction in the treatment of irinotecan-induced gastrointestinal toxicity.Methods:A network pharmacology approach was used to analyze the active compounds,dr...Objective:To find out the potential mechanisms of Huangqin decoction in the treatment of irinotecan-induced gastrointestinal toxicity.Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of Huangqin decoction in treating irinotecan-induced gastrointestinal toxicity.The compounds and predicted targets of Huangqin decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the Huangqin decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway(KEGG)enrichment analyses.Results:The results show that 161compounds and 143 targets were obtained in this work.These targets were further mapped to 216 GO biological process terms and 30 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network.These results indicated that Huangqin decoction may treat the irinotecan-induced gastrointestinal toxicity mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusion:This study confirmed that the active components of Huangqin decoction play an important role in the treatment of irinotecan-related gastrointestinal toxicity through multi-target and multi-pathway,which provides a new way for the pathogenesis of irinotecan-related gastrointestinal toxicity.It facilitates the modernization of herbal medicine for complex diseases in the future.展开更多
Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice...Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of HQD.Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each group.Except for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse model.The mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of Nrf2,HO-1,and inhibitory KELCH like ECH-related protein 1(Keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,respectively.Results:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic acid.Compared to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(P<0.05),whereas the expressions of Nrf2 and HO-1 were significantly decreased,and the expression of Keap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.Conclusion:HQD may regulate the expression of Nrf2 and HO-1 in colon tissue,reduce the expression of MDA and increase the expression of SOD in serum,thus delaying the progress of CAC in AOM/DSS mice.展开更多
Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with ...Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with HQC.Methods:A total of 40 SD rats were randomly divided into the normal group,model group,western medicine treatment group,and HQC group,with 10 rats in each group,and the RA model was induced by complete adjuvant in all groups except the normal group.After successful modeling,they were treated for 4 weeks to compare the degree of joint swelling;meanwhile,micro-CT was used to evaluate bone microstructural parameters,and changes in serum TLR4 and NF-kB expression levels were detected by ELISA.Results:There was no statistical significance in comparing the degree of joint swelling among the model group,western medicine treatment group and HQC group(P>0.05);Micro-CT results showed that bone microstructural parameters deteriorated in the osteoporosis model group compared with the normal group.Both western medicine and traditional Chinese medicine HQC could improve the bone microjunction of RA rats,and the HQC group was better than the western medicine treatment in improving the number of bone trabeculae(2.58±0.19)·mm^(-1);the serum results showed that RA was accompanied by the up-regulation of the expression of TLR4 and NF-kB.Both western drugs and HQC down-regulated the high expression of serum TLR4 and NF-kB in osteoporotic rats,and the down-regulation of serum TLR4(9.90±0.55)ng·ml^(-1)and NF-kB(350.29±3.14)ng·L^(-1)by HQC was more obvious.Conclusion:Chinese herbal medicine HQC can significantly improve the bone microstructure of RA rats,and its effect is better than that of western medicine in some aspects.The mechanism of action of HQC is related to the inhibition of the activation of the TLR4/NF-kB pathway,and this study provides an experimental basis for the further development and utilization of HQC.展开更多
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
基金Supported by National Natural Science Foundation of China,No.82260957,No.82274610,No.81860819and No.81960818+4 种基金Guizhou Provincial Science and Technology Program(Qian Kehe Foundation-ZK[2022]General 498,Qian Kehe Foundation-ZK[2022]General 487,Qian Kehe Support[2021]General 095,Qian Kehe Platform Talent[2020]5013)National Key R&D Program Project(2019YFC1712504)Guizhou Traditional Chinese Medicine Tumor Inheritance and Science and Technology Innovation Talent Base(No.Deaf leader-[2018]No.3)Guizhou high-level innovative talent training plan(100 levels)(No.Qian Kehe Talents[2016]No.4032)Yang Zhu,Guizhou Province,“Traditional Chinese Medicine Oncology”Graduate Tutor Studio(No.Teaching and research GZS-[2016]08)
文摘BACKGROUND To analyze the potential action mechanism of Huangqin decoction(HQD)in colorectal cancer(CRC)treatment on the basis of network pharmacology and molecular docking.AIM To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking.METHODS All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine.Then,the targets of the active ingredients were screened.The abbreviations of protein targets were obtained from the UniProt database.A“drug–compound–target”network was constructed to screen for some main active ingredients.Some targets related to the therapeutic effect of CRC were obtained from the GeneCards,DisGeNET,Therapeutic Target Database,and Online Mendelian Inheritance in Man databases.The intersection of targets of Chinese herbs and CRC was taken.A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database.Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC.The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization.Finally,molecular docking was performed using AutoDockTool and PyMOL for validation.RESULTS In total,280 potential drug-active ingredients were present in HQD,including 1474 targets of the drug-active ingredients.The main active ingredients identified were betulin,tetrahydropalmatine,and quercetin.In total,10249 CRC-related targets and 1014 drug-disease intersecting targets were identified,including 28 core targets of action such as Jun proto-oncogene,AP-1 transcription factor subunit,signal transducer and activator of transcription 3,tumor protein p53,vascular endothelial growth factor,and AKT serine/threonine kinase 1.The gene ontology enrichment functional analysis yielded 503 enrichment results,including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia,etc.In total,38 cellular components were primarily related to polymer complexes,transcription factor complexes,and platelet alpha granule lumen.Then,59 molecular functions were closely related to the binding of enzymes,homologous proteins,and transcription factors.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results,involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways.CONCLUSION HQD can play a role in CRC treatment through the“multi-component-target–pathway”.The active ingredients betulin,tetrahydropalmatine,and quercetin may act on targets such as Jun proto-oncogene,AP-1 transcription factor subunit,signal transducer and activator of transcription 3,tumor protein p53,vascular endothelial growth factor,and AKT serine/threonine kinase 1,which in turn regulate HIF-1 and mitogen-activated protein kinase signaling pathways in CRC treatment.The molecular docking junction clarified that all four key target proteins could bind strongly to the main HQD active ingredients.This indicates that HQD could slow down CRC progression by modulating multiple targets and signaling pathways.
基金The research is financially supported by the Natural Science Research Projects in Anhui Universities[No.KJ2020A0438].
文摘Background:Through the use of network pharmacology and molecular docking approaches,this study will examine the pharmacological effects of Sanwu Huangqin Tang on restless legs syndrome in order to better understand the mechanism of action of Traditional Chinese medicine(TCM)on RLS.Method:Utilise the TCMSP database to collect and select the drug components of Sanwu Huangqin Tang,and the Uniprot database to identify pertinent targets;RLS-related disease targets were obtained from GeneCards,DrugBank,and OMIM databases;and STRING and Cytoscape 3.9.1 software were used to generate an interaction network.KEGG pathway analysis and GO enrichment analysis were performed utilizing the DAVID database.Use Autodock for analyzing the relationships between targets and core components.Result:By using a network pharmacology approach,83 active ingredients and 50 drug-disease intersecting targets were derived for Sanwu Huangqin Tang.The molecular docking results showed that the drug components had strong affinity with the average target targets.Conclusions:This study provides new insights into the mechanism through which Traditional Chinese Medicine(TCM)treats Restless Legs Syndrome(RLS).Furthermore,it lays the foundation for additional research into the mechanism of treatment for RLS through the intervention that addresses various targets and pathways using the active ingredients identified by Sanwu Huangqin Tang.
基金General Project of Heilongjiang Provincial Natural Science Foundation(No.H2017064)
文摘Objective:To analyze the main compounds of Sanwu Huangqin decoction based on the method of network pharmacology and to predict its possible target and mechanism of action in the treatment of Behcet's disease(BD).Methods:TCMSP,TCMID and literatures were used to search the main compounds and their corresponding targets of Sanwu Huangqin Decoction;the disease targets of BD were searched by GeneCards database;the intersection targets of Sanwu Huangqin Decoction and BD were visualized by String database and Cytoscape software;the intersection targets were enriched by GO and KEGG by DAVID database;BD mouse model was established,RT-PCR was used to verify the regulatory effect of Sanwu Huangqin Decoction on the core target genes.Results:A total of 81 main active compounds and 50 drug-disease-target were retrieved from the databases.There were 531 biological function information and 96 signal pathways were enriched by GO and KEGG.Among them,the top 5 signal pathways were Fluid shear stress and atherosclerosis、AGE-RAGE signaling pathway in diabetic complications、IL-17 signaling pathway、TNF signaling pathway、Malaria、Chagas disease(American trypanosomiasis).RT-PCR results showed that the expression of IL-4,IL-1β,IL-6,INF-γmRNA in the spleen of BD mice was significantly up-regulated,and the expression of Caspase 3 and Caspase 8 mRNA was significantly down regulated when compared with the control group(P<0.01).Compared with the model group,the expression of IL-4,IL-1β,IL-6,INF-γmRNA in the Sanwu Huangqin decoction group was significantly down regulated,and the expression of caspase 3 and caspase 8 mRNA was significantly up regulated(P<0.01).Conclusion:Sanwu Huangqin decoction can treat BD through multi-target and multi-channel therapy,and our study and our research provides bioinformatics basis for further revealing its mechanism and treatment.
基金General Project of Natural Science Funds of Heilongjiang Province(No.H2017064)
文摘Objective:To investigate the effect of Sanwu Huangqin Decoction on IFN-γand IL-17A levels in mice with Behcet's disease;Methods:Clinical samples of patients with Behcet's disease were collected and mononuclear cells were isolated.High throughput RNA-seq was used to identify the different genes between Behcet's disease and healthy subjects.Mouse model was constructed by shrimp myosin sensitization and treated with Sanwu Huangqin decoction.The levels of IFN-γand IL-17A in peripheral blood and mononuclear cells were detected by ELISA and flow cytometry.The expression level of TBX21 gene in spleen was detected by RT-PCR;Results:Compared with healthy subjects,31 differential genes were identified in BD patients,of which 19 genes were up-regulated and 12 genes were down regulated.PPI analysis showed that the top 5 genes were TBX21,STAT3,IL15,PRF1 and IFNG.The results of animal experiments showed that the levels of IFN-γand IL-17A in the peripheral blood and PBMC of the model group were significantly higher compared with the control group(P<0.01).Sanwu Huangqin decoction could significantly reduce the levels of IFN-γand IL-17A in the peripheral blood and PBMC of mice(P<0.05 or P<0.01).RT-PCR results showed that the expression of TBX21 mRNA in spleen tissue of model group was significantly higher than that of the control group(P<0.01).Sanwu Huangqin decoction could significantly down-regulate the expression of TBX21 mRNA in spleen(P<0.05 or P<0.01);Conclusion:Sanwu Huangqin decoction reduce the levels of IFN-γand IL-17A by inhibiting the expression of TBX21 mRNA,so as to achieve the effect of treating BD.
文摘Objective:To find out the potential mechanisms of Huangqin decoction in the treatment of irinotecan-induced gastrointestinal toxicity.Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of Huangqin decoction in treating irinotecan-induced gastrointestinal toxicity.The compounds and predicted targets of Huangqin decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the Huangqin decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway(KEGG)enrichment analyses.Results:The results show that 161compounds and 143 targets were obtained in this work.These targets were further mapped to 216 GO biological process terms and 30 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network.These results indicated that Huangqin decoction may treat the irinotecan-induced gastrointestinal toxicity mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusion:This study confirmed that the active components of Huangqin decoction play an important role in the treatment of irinotecan-related gastrointestinal toxicity through multi-target and multi-pathway,which provides a new way for the pathogenesis of irinotecan-related gastrointestinal toxicity.It facilitates the modernization of herbal medicine for complex diseases in the future.
基金Supported by the Natural Science Foundation Project of Nanjing University of Traditional Chinese Medicine(No.XZR2020030)Jiangsu Famous Traditional Chinese Medicine Inheritance Studio Project(Jiangsu Traditional Chinese Medicine Science and Education(No.20SGzs003)。
文摘Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of HQD.Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each group.Except for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse model.The mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of Nrf2,HO-1,and inhibitory KELCH like ECH-related protein 1(Keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,respectively.Results:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic acid.Compared to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(P<0.05),whereas the expressions of Nrf2 and HO-1 were significantly decreased,and the expression of Keap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.Conclusion:HQD may regulate the expression of Nrf2 and HO-1 in colon tissue,reduce the expression of MDA and increase the expression of SOD in serum,thus delaying the progress of CAC in AOM/DSS mice.
文摘Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with HQC.Methods:A total of 40 SD rats were randomly divided into the normal group,model group,western medicine treatment group,and HQC group,with 10 rats in each group,and the RA model was induced by complete adjuvant in all groups except the normal group.After successful modeling,they were treated for 4 weeks to compare the degree of joint swelling;meanwhile,micro-CT was used to evaluate bone microstructural parameters,and changes in serum TLR4 and NF-kB expression levels were detected by ELISA.Results:There was no statistical significance in comparing the degree of joint swelling among the model group,western medicine treatment group and HQC group(P>0.05);Micro-CT results showed that bone microstructural parameters deteriorated in the osteoporosis model group compared with the normal group.Both western medicine and traditional Chinese medicine HQC could improve the bone microjunction of RA rats,and the HQC group was better than the western medicine treatment in improving the number of bone trabeculae(2.58±0.19)·mm^(-1);the serum results showed that RA was accompanied by the up-regulation of the expression of TLR4 and NF-kB.Both western drugs and HQC down-regulated the high expression of serum TLR4 and NF-kB in osteoporotic rats,and the down-regulation of serum TLR4(9.90±0.55)ng·ml^(-1)and NF-kB(350.29±3.14)ng·L^(-1)by HQC was more obvious.Conclusion:Chinese herbal medicine HQC can significantly improve the bone microstructure of RA rats,and its effect is better than that of western medicine in some aspects.The mechanism of action of HQC is related to the inhibition of the activation of the TLR4/NF-kB pathway,and this study provides an experimental basis for the further development and utilization of HQC.
