As a traditional Chinese medicine,Curcumae Radix(CR)has exhibited anti-hepatocellular carcinoma(HCC)activity.However,the underlying molecular mechanism is still unclear.In the present study,network pharmacology was ut...As a traditional Chinese medicine,Curcumae Radix(CR)has exhibited anti-hepatocellular carcinoma(HCC)activity.However,the underlying molecular mechanism is still unclear.In the present study,network pharmacology was utilized to reveal the mechanism of the effects of CR in HCC.The analysis of the network results showed that the active components of CR,including curcumin,naringenin,sitosterol,demethoxycurcumin,andβ-elemene,were closely related to the screened hub-targets,such as AKT1,TP53,MAPK8,MAPK1,JUN,STAT3,VEGFA,MAPK3,IL6,TNF,CCND1,EP300,EGFR,and ESR1.GO and KEGG analyses revealed that these targets were associated with pathways in cancer,proteoglycans in cancer,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway,hepatitis B,hepatitis C,and other biological processes.The candidate active components of CR(curcumin and naringenin)prominently exhibited their antitumor effects by regulating PI3K-Akt signaling pathway,MAPK signaling pathway,hepatitis B and hepatitis C.This study successfully predicted,explained,and confirmed the multi-component,multi-target,and multi-channel characteristics of CR,which not only gave novel insights into the pharmacological and biological molecular mechanism of CR applying to HCC disease,but also provided a feasible method for discovering potential activated compounds from Chinese herbs.展开更多
OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combinatio...OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.展开更多
Objective: This study aimed to investigate the network pharmacology of curcumae radix(CR, Yujin) and explore the mechanism of CR in the treatment of cerebral ischemia-reperfusion injury(CIRI). Materials and Methods: N...Objective: This study aimed to investigate the network pharmacology of curcumae radix(CR, Yujin) and explore the mechanism of CR in the treatment of cerebral ischemia-reperfusion injury(CIRI). Materials and Methods: Network analysis and pharmacological evaluation were performed to explore the protective role of CR to treat CIRI. The potential target genes of the active components and CIRI were identified using SwissTarget Prediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, GeneCards, and Online Mendelian Inheritance in Man. Furthermore, network analysis was performed using Cytoscape software.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the R software. In vivo experiments were performed using the water extract of CR(WECR) on PC12 cells induced by hypoxia/reoxygenation(H/R) to simulate ischemia/reperfusion injury. Results: The results exhibited that 21 active compounds identified in CR were associated with 73 targets of CIRI. Functional analysis showed that multiple pathways, including response to stress, regulation of apoptotic process, and hypoxia-inducible factor 1 signaling pathway, were significantly enriched. In addition, STAT3, IL4, HIFIA, and CTNNB1 were predicted to be the most important genes among the 36 hub genes. Furthermore, WECR treatment significantly improved PC12 cell injury and decreased apoptosis levels in cells induced by H/R, with malondialdehyde contents reduced and superoxide dismutase or glutathione peroxidase levels increased. Conclusions: Network analysis and pharmacological evaluation of CR could provide valuable directions for further research on CR and improve comprehension of CIRI.展开更多
A comparison of the volatile compounds in Rhizomes Curcumae （Ezhu） and Radix Curcumae （Yujin） was undertaken using gas chromatography mass spectrometi-y （GC-MS）. Ultrasonic extraction and GC-MS methods were deve...A comparison of the volatile compounds in Rhizomes Curcumae （Ezhu） and Radix Curcumae （Yujin） was undertaken using gas chromatography mass spectrometi-y （GC-MS）. Ultrasonic extraction and GC-MS methods were developed for the simultaneous determination of five sesquiterpenes, namely, α-pinene, β-elemene, curcumol, germacrone and curdione, in Ezhu and Yunjin. Good linearity （r〉0.999） and high inter-day precision were observed over the investigated concentration ranges. The validated method was successfully used for the simultaneous determination of five sesquiterpenes in Ezhu and Yujin. The quantitative method can be effectively used to evaluate and monitor the quality of Chinese curcuma in clinical use.展开更多
To study the effect of chinese herbal medicine preventing gallstone formation, morphology of livers and gallbladders as well as conjugated bile acids of the bile. 58 female guinea pigs were randomly divided into three...To study the effect of chinese herbal medicine preventing gallstone formation, morphology of livers and gallbladders as well as conjugated bile acids of the bile. 58 female guinea pigs were randomly divided into three groups. The control group was fed on normal diet; the lithogenous groups was high cholesterol diet (HCD) and the antilithic group was high cholesterol and the chinese herbal medicine capsule (13 5 g/kg). 8 weeks later the guinea pigs were killed. Liver and gallbladder were removed for light and electroscope observation. Gallbladder bile were withdrawn and gallbladder were collected. The minute construction of gallstones were observed by scanning electron microscope and gallstone components were quantified by Fourier Transform Infrand Spectros Copy (FT IR). The morphology of liver and gallbladder were observed by light microscope and transmission electron microscope. Conjugated bile acid of biles were determined by Thin layer Chromatograph. The effect of chinese herbal medicine preventing gallstone formation, morphololgy of livers and gallbladders as well as conjugated bile acids of the bile were also observed. We measured conjugated bile acids in all groups and found that decreased in lithogenic group and increased notably in antilithic group (P<0 01) . The gallstone formation rate was 100% when the animals were fed on HCD in lithogenic group. The rate decreased to 5 3% when the animals were fed on HCD and Chinese herbal medicine capsule inantilithic group. It indicates that changes in diet is an important factor in the process of gallstone formation and the chinese herbal medicine can prevent gallstone formation effectively.展开更多
文摘As a traditional Chinese medicine,Curcumae Radix(CR)has exhibited anti-hepatocellular carcinoma(HCC)activity.However,the underlying molecular mechanism is still unclear.In the present study,network pharmacology was utilized to reveal the mechanism of the effects of CR in HCC.The analysis of the network results showed that the active components of CR,including curcumin,naringenin,sitosterol,demethoxycurcumin,andβ-elemene,were closely related to the screened hub-targets,such as AKT1,TP53,MAPK8,MAPK1,JUN,STAT3,VEGFA,MAPK3,IL6,TNF,CCND1,EP300,EGFR,and ESR1.GO and KEGG analyses revealed that these targets were associated with pathways in cancer,proteoglycans in cancer,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway,hepatitis B,hepatitis C,and other biological processes.The candidate active components of CR(curcumin and naringenin)prominently exhibited their antitumor effects by regulating PI3K-Akt signaling pathway,MAPK signaling pathway,hepatitis B and hepatitis C.This study successfully predicted,explained,and confirmed the multi-component,multi-target,and multi-channel characteristics of CR,which not only gave novel insights into the pharmacological and biological molecular mechanism of CR applying to HCC disease,but also provided a feasible method for discovering potential activated compounds from Chinese herbs.
基金National Natural Science Foundation of China Youth Found Project:Anti-Colorectal Cancer Metastasis Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)According to the Hypoxia-Inducible Factor 2 Alpha/β-Catenin Cross-Talk Which Influence the Colon Tumor Stem Cells in Hypoxia Microenvironment(No.82003961)National Natural Science Foundation of China Youth Found Project:the Mechanism of the Compatibility of Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis)on the Early Metastasis of Hepatocellular Carcinoma Mediated by Cancer Associated Fibroblasts(82104408)+1 种基金Science Foundation of China Project:Involvement of Hypoxia Inducible Factor-1αSignal in Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Combination Induced Remolding of Tumor Hypoxic Microenvironment(No.82074035)Science and Technology Development Project of Traditional Chinese Medicine in Jiangsu Province:Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Herb Pair on the Inhibition of Colon Cancer Metastasis Through the Wnt/β-catenin Pathway(No.YB201921)。
文摘OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.
基金the funding support from national major science and technology project for Significant New Drugs Creation"(2017ZX09309026)the National Natural Science Foundation of China(grant no.81874464)+1 种基金Hunan postgraduate innovation project(CX20190566)postgraduate innovation project of Hunan University of Chinese Medicine(2018CX70).
文摘Objective: This study aimed to investigate the network pharmacology of curcumae radix(CR, Yujin) and explore the mechanism of CR in the treatment of cerebral ischemia-reperfusion injury(CIRI). Materials and Methods: Network analysis and pharmacological evaluation were performed to explore the protective role of CR to treat CIRI. The potential target genes of the active components and CIRI were identified using SwissTarget Prediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, GeneCards, and Online Mendelian Inheritance in Man. Furthermore, network analysis was performed using Cytoscape software.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the R software. In vivo experiments were performed using the water extract of CR(WECR) on PC12 cells induced by hypoxia/reoxygenation(H/R) to simulate ischemia/reperfusion injury. Results: The results exhibited that 21 active compounds identified in CR were associated with 73 targets of CIRI. Functional analysis showed that multiple pathways, including response to stress, regulation of apoptotic process, and hypoxia-inducible factor 1 signaling pathway, were significantly enriched. In addition, STAT3, IL4, HIFIA, and CTNNB1 were predicted to be the most important genes among the 36 hub genes. Furthermore, WECR treatment significantly improved PC12 cell injury and decreased apoptosis levels in cells induced by H/R, with malondialdehyde contents reduced and superoxide dismutase or glutathione peroxidase levels increased. Conclusions: Network analysis and pharmacological evaluation of CR could provide valuable directions for further research on CR and improve comprehension of CIRI.
基金supported by the National Natural Science Foundation of China (no.30873196)the Project of Modernization of Traditional Chinese Medicine of Shanghai (no.09dZ1975100)
文摘A comparison of the volatile compounds in Rhizomes Curcumae （Ezhu） and Radix Curcumae （Yujin） was undertaken using gas chromatography mass spectrometi-y （GC-MS）. Ultrasonic extraction and GC-MS methods were developed for the simultaneous determination of five sesquiterpenes, namely, α-pinene, β-elemene, curcumol, germacrone and curdione, in Ezhu and Yunjin. Good linearity （r〉0.999） and high inter-day precision were observed over the investigated concentration ranges. The validated method was successfully used for the simultaneous determination of five sesquiterpenes in Ezhu and Yujin. The quantitative method can be effectively used to evaluate and monitor the quality of Chinese curcuma in clinical use.
文摘To study the effect of chinese herbal medicine preventing gallstone formation, morphology of livers and gallbladders as well as conjugated bile acids of the bile. 58 female guinea pigs were randomly divided into three groups. The control group was fed on normal diet; the lithogenous groups was high cholesterol diet (HCD) and the antilithic group was high cholesterol and the chinese herbal medicine capsule (13 5 g/kg). 8 weeks later the guinea pigs were killed. Liver and gallbladder were removed for light and electroscope observation. Gallbladder bile were withdrawn and gallbladder were collected. The minute construction of gallstones were observed by scanning electron microscope and gallstone components were quantified by Fourier Transform Infrand Spectros Copy (FT IR). The morphology of liver and gallbladder were observed by light microscope and transmission electron microscope. Conjugated bile acid of biles were determined by Thin layer Chromatograph. The effect of chinese herbal medicine preventing gallstone formation, morphololgy of livers and gallbladders as well as conjugated bile acids of the bile were also observed. We measured conjugated bile acids in all groups and found that decreased in lithogenic group and increased notably in antilithic group (P<0 01) . The gallstone formation rate was 100% when the animals were fed on HCD in lithogenic group. The rate decreased to 5 3% when the animals were fed on HCD and Chinese herbal medicine capsule inantilithic group. It indicates that changes in diet is an important factor in the process of gallstone formation and the chinese herbal medicine can prevent gallstone formation effectively.
