This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further...This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further research ideas for clinical researchers.展开更多
Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to ...Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill.The main active components of the medicine were screened through the network analysis function of Cytoscape software,and the target of the main active components of the medicine was found in UniProt database.Using genecards,OMIM,digsee,TTD,and drugbank database to retrieve the related targets of ovarian cancer.The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software.The intersection targets are imported into string database for PPI analysis,and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in.KEGG pathway analysis and go enrichment analysis were carried out in metascape database.At last,autodock tools was used to verify the main active ingredients and the selected target proteins.PyMOL and LigPlus software visualized the results.Results:The main active components of Guizhi Fuling pills were quercetin,β-sitosterol,kaempferol,hederagenin,catechin,ellagic acid,stigmasterol and Douglas fir.There are 20 pivotal genes of drug effect on ovarian cancer,including VEGFA,AKT1,mapk8,Jun,MMP9,IL6,TNF,CXCL8,PTGS2,TP53,CASP3,mapk1,EGF,ESR1,EGFR,Myc,FOS,CCL2,CXCL8 and IL1B.According to KEGG pathway analysis,10 pathways with the highest correlation were found:cancer signaling pathway,MAPK signaling pathway,fluid shear stress and atherosclerosis,hepatitis B,trypanosomiasis,age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,pertussis,IL-17 signaling pathway,and bladder cancer.Go enrichment analysis has screened out 10 important items in molecular biological function,cell components and biological process.The proteins encoded by IL6,mapk1,VEGFA,AKT1,TP53,TNF and CCL2 were used as targets to dock with the main active components of the drug respectively,and the best results were TNFαand ellagic acid.Conclusion:The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6,VEGFA,CCL2,TNF,MMP9 and other cytokines,and inhibit the proliferation and metastasis of cancer cells.展开更多
Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME f...Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME features on Traditional Chinese Medicine Systems Pharmacology platform,and their targets were obtained.Targets of atherosclerosis were extracted and screened from GeneCards database,OMIM database,DrugBank database and DisGeNET database,and the intersection of component targets and disease targets were regarded as potential targets.The protein-protein interaction network of potential targets was constructed by STRING database and Cytoscape 3.7.2.GO analysis and KEGG pathway analysis of potential targets were performed by Metascape platform.The“drugs-componenst-targets-pathways”network was constructed by Cytoscape 3.7.2.SwissDock was used for molecular docking of active components and key targets.Results:The main components of Guizhi Fuling pill in the treatment of atherosclerosis were quercetin,beta-sitosterol,kaempfero,hederagenin,baicalein,etc.The key targets mainly included PGST2,RELA,AKT1,etc.Molecular docking analysis showed that the binding energy of the main active components to the core target was less than-7 kcal/mol.The associated pathways mainly included fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway and AGE-RAGE signaling pathway.Conclusion:Through this study,we initially revealed the possible mechanism of Guizhi Fuling pill in treating atherosclerosis through anti-inflammatory,reducing blood lipids,and regulating endothelial function.展开更多
OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fraction...OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.展开更多
Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and meta...Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and metadherin(MTDH).METHODS Guizhi Fuling Wan(GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition,Wistar rats were given GFW viagavage at 4 g·kg^(-1)·d^(-1),8 g·kg^(-1)·d^(-1),16 g·kg^(-1)·d^(-1),or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera,medium-dose sear,highdose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells.Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells.RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera.RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli.taxel,the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold,respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec.tively;there was a significant difference between the groups(P<0.01).RT-qPCR results showed that,compared with the blank serum,the sera can up-regulate the expression of PTEN mRNA and downregulate the expression of MTDH mRNA in a dose-dependent manner.Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement.CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH,up-regulation of PTEN and induction of apoptosis,providing with an experiment basis for the applica.tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.展开更多
Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroid...Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroids who were treated in our hospital from August 2016 to August 2017 were selected according to the order of treatment and divided into observation group and control group, 60 cases each. Mifepristone was administered to the control group and mifepristone combined with Guizhi Fuling Capsules was administered to the observation group. The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups.Result:The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups. After treatment, hemoglobin levels increased significantly in the two groups, VEGF, sex hormones FSH, LH and E2, tumor markers HE4, CA125, inflammatory cytokines TNF-α and IFN-γ levels decreased significantly. The hemoglobin level of the observation group was (117.09±11.51) g/L higher than that of the control group , and the level of VEGF was (0.69±0.06) pg/mL lower than that of the control group. The levels of sex hormone FSH, LH and E2 in the observation group were (15.87±1.56) U/L, (10.69±1.06) U/L and (4.95±0.51) pmol/L lower than those of the control group. The levels of HE4, CA125, TNF-α and IFN-γ gamma in the observation group were (52.47±5.24) pmol/L, (15.46±1.53) U/mL, (40.41±4.05) and (16.72±1.62) pg/mL lower than those of the control group.Conclusion:Guizhi Fuling Capsule can significantly improve the level of sex hormones and tumor markers, relieve inflammatory stress and improve the therapeutic effect.展开更多
Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis...Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.展开更多
文摘This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further research ideas for clinical researchers.
基金National Natural Science Foundation of China(No.81473566)。
文摘Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill.The main active components of the medicine were screened through the network analysis function of Cytoscape software,and the target of the main active components of the medicine was found in UniProt database.Using genecards,OMIM,digsee,TTD,and drugbank database to retrieve the related targets of ovarian cancer.The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software.The intersection targets are imported into string database for PPI analysis,and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in.KEGG pathway analysis and go enrichment analysis were carried out in metascape database.At last,autodock tools was used to verify the main active ingredients and the selected target proteins.PyMOL and LigPlus software visualized the results.Results:The main active components of Guizhi Fuling pills were quercetin,β-sitosterol,kaempferol,hederagenin,catechin,ellagic acid,stigmasterol and Douglas fir.There are 20 pivotal genes of drug effect on ovarian cancer,including VEGFA,AKT1,mapk8,Jun,MMP9,IL6,TNF,CXCL8,PTGS2,TP53,CASP3,mapk1,EGF,ESR1,EGFR,Myc,FOS,CCL2,CXCL8 and IL1B.According to KEGG pathway analysis,10 pathways with the highest correlation were found:cancer signaling pathway,MAPK signaling pathway,fluid shear stress and atherosclerosis,hepatitis B,trypanosomiasis,age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,pertussis,IL-17 signaling pathway,and bladder cancer.Go enrichment analysis has screened out 10 important items in molecular biological function,cell components and biological process.The proteins encoded by IL6,mapk1,VEGFA,AKT1,TP53,TNF and CCL2 were used as targets to dock with the main active components of the drug respectively,and the best results were TNFαand ellagic acid.Conclusion:The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6,VEGFA,CCL2,TNF,MMP9 and other cytokines,and inhibit the proliferation and metastasis of cancer cells.
基金This study was supported by National Science Foundation of China(81973645,81673805,81704058,and 81774100)Natural Science Foundation of Guangdong(2019A1515011560)Traditional Chinese Medicine Bureau of Guangdong Province(20161167,20201392).
文摘Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME features on Traditional Chinese Medicine Systems Pharmacology platform,and their targets were obtained.Targets of atherosclerosis were extracted and screened from GeneCards database,OMIM database,DrugBank database and DisGeNET database,and the intersection of component targets and disease targets were regarded as potential targets.The protein-protein interaction network of potential targets was constructed by STRING database and Cytoscape 3.7.2.GO analysis and KEGG pathway analysis of potential targets were performed by Metascape platform.The“drugs-componenst-targets-pathways”network was constructed by Cytoscape 3.7.2.SwissDock was used for molecular docking of active components and key targets.Results:The main components of Guizhi Fuling pill in the treatment of atherosclerosis were quercetin,beta-sitosterol,kaempfero,hederagenin,baicalein,etc.The key targets mainly included PGST2,RELA,AKT1,etc.Molecular docking analysis showed that the binding energy of the main active components to the core target was less than-7 kcal/mol.The associated pathways mainly included fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway and AGE-RAGE signaling pathway.Conclusion:Through this study,we initially revealed the possible mechanism of Guizhi Fuling pill in treating atherosclerosis through anti-inflammatory,reducing blood lipids,and regulating endothelial function.
基金supported by National Science and Technology Major Projects of China(2013ZX09402203,2013ZX09508104)Medical and Health Science and Technology Innovation Engineering of Chinese Academy of Medical Sciences(2016-I2M-3-007)National Natural Science Foundation of China(81573454)
文摘OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.
基金supported by Natural Science Foundation of Henan Province (162300410204)
文摘Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and metadherin(MTDH).METHODS Guizhi Fuling Wan(GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition,Wistar rats were given GFW viagavage at 4 g·kg^(-1)·d^(-1),8 g·kg^(-1)·d^(-1),16 g·kg^(-1)·d^(-1),or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera,medium-dose sear,highdose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells.Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells.RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera.RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli.taxel,the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold,respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec.tively;there was a significant difference between the groups(P<0.01).RT-qPCR results showed that,compared with the blank serum,the sera can up-regulate the expression of PTEN mRNA and downregulate the expression of MTDH mRNA in a dose-dependent manner.Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement.CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH,up-regulation of PTEN and induction of apoptosis,providing with an experiment basis for the applica.tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.
文摘Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroids who were treated in our hospital from August 2016 to August 2017 were selected according to the order of treatment and divided into observation group and control group, 60 cases each. Mifepristone was administered to the control group and mifepristone combined with Guizhi Fuling Capsules was administered to the observation group. The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups.Result:The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups. After treatment, hemoglobin levels increased significantly in the two groups, VEGF, sex hormones FSH, LH and E2, tumor markers HE4, CA125, inflammatory cytokines TNF-α and IFN-γ levels decreased significantly. The hemoglobin level of the observation group was (117.09±11.51) g/L higher than that of the control group , and the level of VEGF was (0.69±0.06) pg/mL lower than that of the control group. The levels of sex hormone FSH, LH and E2 in the observation group were (15.87±1.56) U/L, (10.69±1.06) U/L and (4.95±0.51) pmol/L lower than those of the control group. The levels of HE4, CA125, TNF-α and IFN-γ gamma in the observation group were (52.47±5.24) pmol/L, (15.46±1.53) U/mL, (40.41±4.05) and (16.72±1.62) pg/mL lower than those of the control group.Conclusion:Guizhi Fuling Capsule can significantly improve the level of sex hormones and tumor markers, relieve inflammatory stress and improve the therapeutic effect.
基金This work was supported by the National Natural Science Foundation of China(No.82074348)the Taishan Scholar Project(tsqn201812145)the Key Technology Research and Development Program of Shandong(No.2019GSF108162).
文摘Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.