BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The...BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.展开更多
Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal ...Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.展开更多
To clarify the active components of Wuzhuyu-tang, this study analyzed dynamic changes of 10 ingredients of Wuzhuyu-tang in plasma using combination high performance liquid chromatography-mass spectrometry after oral a...To clarify the active components of Wuzhuyu-tang, this study analyzed dynamic changes of 10 ingredients of Wuzhuyu-tang in plasma using combination high performance liquid chromatography-mass spectrometry after oral administration in rats. The results showed that seven ingredients were detected in portal vein plasma after oral administration of 16.3 or 8.15 g/kg equivalent of raw material of Wuzhuyu-tang extract. The absorption rate of limonin, evodiamine, gingerol （6-Gi）, and ginsenoside-Rg1 was greater than that of isorhamnetin-3-O-β-D-glucosyl （6″→1″′）-α-L-rhamnoside, ginsenoside-Rb1 （Rb1）, and ginsenoside-Re （Re）. The time most elements were absorbed into the blood was 30 to 60 minutes after administration. Re, 6-Gi and Rb1 were metabolized faster. The results suggest that the seven ingredients described above are the active components for treating migraines.展开更多
A reversed-phase high-performance liquid chromatography （RP-HPLC） method with diode array detector was established to simultaneously determine nine bioactive compounds in Wuzhuyu decoction, namely dehydroevodiamine,...A reversed-phase high-performance liquid chromatography （RP-HPLC） method with diode array detector was established to simultaneously determine nine bioactive compounds in Wuzhuyu decoction, namely dehydroevodiamine, isorhanmetin-7-O- rutinoside, 10-hydroxyrutaecarpine, diosmetin-7-O-13-D-glucopyranoside, evodiamine, rutaecarpine, 1-metbyl-2-n-nonyl-4（1H） quinolone, evocarpine, and dihydroevocarpine. The RP-HPLC assay was performed on a reversed-phase Cl8 column with a gradient elution. The mobile phases consisted of methanol and water containing 1% （v/v） acetic acid. The flow rate was 1.0 mL/min and the detection wavelength was set at 300 nm. All calibration curves showed good linearity （r2〉0.9941） within test ranges. The results of intra-day precision, inter-day precision, and accuracy were satisfactory. The overall recoveries were in the range of 90.13%-102.48%. The method was successfully applied to quantify nine bioactive compounds in six samples. Baseline resolution for all nine major compounds was achieved. This method could be used as a suitable quality control assay for Wuzhuyu decoction.展开更多
Objective： To study the efficacy of modified Wuzhuyu Decoction Granule （加减吴茱萸汤颗粒剂, MWDG） in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. Methods： This study was a...Objective： To study the efficacy of modified Wuzhuyu Decoction Granule （加减吴茱萸汤颗粒剂, MWDG） in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. Methods： This study was a randomized, double-blind, placebo-controlled trial. A total of 78 migraine patients with cold and stasis obstructing meridian syndrome were recruited and randomly assigned by a ratio of 2：1 into a treatment group （51 cases） and a placebo group （27 cases）. Patients in the treatment group were treated with MWDG while placebo granules were applied in the control group. The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary outcome measures included frequency and days of migraine attacks and the secondary outcome measures were analgesics consumption and visual analogue scale （VAS） scores. All outcome assessments were conducted respectively at baseline, the 4th, 8th and 12th week, and the end of follow-up. Results： In the treatment group, significant decrease in frequency of migraine attacks were observed since the 4th week and that of analgesics consumption since the 8th week （both P〈0.05）. While, in the placebo group, significant decrease in frequency of migraine attacks were observed since the 8th week and that of analgesics consumption since the 12th week （both P〈0.05）. No significant decrease in days of migraine attacks and VAS scores of migraine pain were observed in both groups. Between the two groups, there were significant differences in VAS scores and intensity of pain appeared in the 8th week （P〈0.05）. However, no significant differences were found in days and frequency of migraine attacks and analgesics consumption （P〉0.05）. Conclusions： MWDG was probably effective in the treatment of migraine especially for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of migraine attacks and analgesics consumption sooner than the placebo.展开更多
OBJECTIVE: To show whether Danggui Sini plus Wuzhuyu Shengjiang Tang(DSWST) has any transient effect on erythrocyte deformability in normal subjects.METHODS: A total of 25 subjects [mean age(27.8± 1.8) years] was...OBJECTIVE: To show whether Danggui Sini plus Wuzhuyu Shengjiang Tang(DSWST) has any transient effect on erythrocyte deformability in normal subjects.METHODS: A total of 25 subjects [mean age(27.8± 1.8) years] was enrolled in this study. The study was designed as a cross-over trial in which the subjects took part for 2 d. On the first day, blood samples were collected at baseline and 1-2 h after administration of water, whereas, on the second day, instead of water, the subjects were administered DSWST after the baseline blood sampling. The blood samples collected at baseline and after the administration water or DSWST, were examined for erythrocyte deformability.RESULTS: The elongation index increased significantly after 2 h(P = 0.009) compared to the baseline after DSWST intake. However, after water intake, there was no significant differenceobserved. When comparing the percent change of erythrocyte deformability between DSWST and water, we found that after 2 h of administration,DSWST improved erythrocyte deformability significantly compared to water(P < 0.001).CONCLUSION: DSWST has a transient effect on erythrocyte deformability in normal subjects.展开更多
基金Supported by the Xiangshan Talented Scientific Research Project of Zhuhai People’s Hospital,No.2021XSYC-02Research Start Project of Zhuhai People’s Hospital,No.2020ycqd001.
文摘BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.
基金supported by the China Natural Science Foundation(No.81973811).
文摘Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.
基金the Scientific Research Program of Beijing Municipal Education Commission-Capital Key Research Program of Chinese Medicine and Nursing, No. 10ZYH01the Supporting Program of the "Eleventh Five-year Plan" for Science and Technology Research of China, No.2006BAI08B03
文摘To clarify the active components of Wuzhuyu-tang, this study analyzed dynamic changes of 10 ingredients of Wuzhuyu-tang in plasma using combination high performance liquid chromatography-mass spectrometry after oral administration in rats. The results showed that seven ingredients were detected in portal vein plasma after oral administration of 16.3 or 8.15 g/kg equivalent of raw material of Wuzhuyu-tang extract. The absorption rate of limonin, evodiamine, gingerol （6-Gi）, and ginsenoside-Rg1 was greater than that of isorhamnetin-3-O-β-D-glucosyl （6″→1″′）-α-L-rhamnoside, ginsenoside-Rb1 （Rb1）, and ginsenoside-Re （Re）. The time most elements were absorbed into the blood was 30 to 60 minutes after administration. Re, 6-Gi and Rb1 were metabolized faster. The results suggest that the seven ingredients described above are the active components for treating migraines.
基金National Sciences and Technology Program of China (Grant No. 2011BAI07B08,2006BAI06A01-02,2006BAI08B03-09)
文摘A reversed-phase high-performance liquid chromatography （RP-HPLC） method with diode array detector was established to simultaneously determine nine bioactive compounds in Wuzhuyu decoction, namely dehydroevodiamine, isorhanmetin-7-O- rutinoside, 10-hydroxyrutaecarpine, diosmetin-7-O-13-D-glucopyranoside, evodiamine, rutaecarpine, 1-metbyl-2-n-nonyl-4（1H） quinolone, evocarpine, and dihydroevocarpine. The RP-HPLC assay was performed on a reversed-phase Cl8 column with a gradient elution. The mobile phases consisted of methanol and water containing 1% （v/v） acetic acid. The flow rate was 1.0 mL/min and the detection wavelength was set at 300 nm. All calibration curves showed good linearity （r2〉0.9941） within test ranges. The results of intra-day precision, inter-day precision, and accuracy were satisfactory. The overall recoveries were in the range of 90.13%-102.48%. The method was successfully applied to quantify nine bioactive compounds in six samples. Baseline resolution for all nine major compounds was achieved. This method could be used as a suitable quality control assay for Wuzhuyu decoction.
基金Supported by the "Eleventh Five-Year Plan" of China State Science&Technology Ministry(No.2007BAI20B053)National Natural Science Foundation of China(No.81273688)
文摘Objective： To study the efficacy of modified Wuzhuyu Decoction Granule （加减吴茱萸汤颗粒剂, MWDG） in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. Methods： This study was a randomized, double-blind, placebo-controlled trial. A total of 78 migraine patients with cold and stasis obstructing meridian syndrome were recruited and randomly assigned by a ratio of 2：1 into a treatment group （51 cases） and a placebo group （27 cases）. Patients in the treatment group were treated with MWDG while placebo granules were applied in the control group. The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary outcome measures included frequency and days of migraine attacks and the secondary outcome measures were analgesics consumption and visual analogue scale （VAS） scores. All outcome assessments were conducted respectively at baseline, the 4th, 8th and 12th week, and the end of follow-up. Results： In the treatment group, significant decrease in frequency of migraine attacks were observed since the 4th week and that of analgesics consumption since the 8th week （both P〈0.05）. While, in the placebo group, significant decrease in frequency of migraine attacks were observed since the 8th week and that of analgesics consumption since the 12th week （both P〈0.05）. No significant decrease in days of migraine attacks and VAS scores of migraine pain were observed in both groups. Between the two groups, there were significant differences in VAS scores and intensity of pain appeared in the 8th week （P〈0.05）. However, no significant differences were found in days and frequency of migraine attacks and analgesics consumption （P〉0.05）. Conclusions： MWDG was probably effective in the treatment of migraine especially for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of migraine attacks and analgesics consumption sooner than the placebo.
文摘OBJECTIVE: To show whether Danggui Sini plus Wuzhuyu Shengjiang Tang(DSWST) has any transient effect on erythrocyte deformability in normal subjects.METHODS: A total of 25 subjects [mean age(27.8± 1.8) years] was enrolled in this study. The study was designed as a cross-over trial in which the subjects took part for 2 d. On the first day, blood samples were collected at baseline and 1-2 h after administration of water, whereas, on the second day, instead of water, the subjects were administered DSWST after the baseline blood sampling. The blood samples collected at baseline and after the administration water or DSWST, were examined for erythrocyte deformability.RESULTS: The elongation index increased significantly after 2 h(P = 0.009) compared to the baseline after DSWST intake. However, after water intake, there was no significant differenceobserved. When comparing the percent change of erythrocyte deformability between DSWST and water, we found that after 2 h of administration,DSWST improved erythrocyte deformability significantly compared to water(P < 0.001).CONCLUSION: DSWST has a transient effect on erythrocyte deformability in normal subjects.
