Objective： To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo. Methods： Transonic alcohol-chloroform extraction meth...Objective： To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo. Methods： Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography （HPLC）. Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract. Results： HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration （IC50, 72 h） was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/（kg·d）] and low-dose [0.138 mg/（kg·d）] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced. Conclusions： Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.展开更多
Two new phenylpropanetriol glycosides, named as meliadanoside A (3 - methoxy- 5 - hydroxy-9- (1' - O-β-D-glucopyranosyl) - threo - phenylpropanetriol ) and meliadanoside B (4- hydroxy-7, 8- (2', 1' - O- ...Two new phenylpropanetriol glycosides, named as meliadanoside A (3 - methoxy- 5 - hydroxy-9- (1' - O-β-D-glucopyranosyl) - threo - phenylpropanetriol ) and meliadanoside B (4- hydroxy-7, 8- (2', 1' - O- β- D -glucopyranosyl) - phenylpropanetriol), were isolated from the water-soluble extract of the fruits of Meliatoosendan Sieb. et Zucc., along with threo-guaiacylglycerol. Their structures were elucidated by spectroscopic and chendcal analysis.展开更多
Two new limonoid-type triterpenoids, named 12-o-ethyl-l-deacetylnimbolinin B and 1-o-tigloyl-1-o-debenzoylohchinal, have been isolated from the fruit of Melia toosendan Sieb. et Zucc. Their structures were elucidated ...Two new limonoid-type triterpenoids, named 12-o-ethyl-l-deacetylnimbolinin B and 1-o-tigloyl-1-o-debenzoylohchinal, have been isolated from the fruit of Melia toosendan Sieb. et Zucc. Their structures were elucidated by spectral methods, including 2D-NMR spectra.展开更多
Two new limonoids,1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12α-ethoxyl nimbolinin（1） and lα-benzoyloxy-3α-acetoxyl-7α- hydroxyl-12α-ethoxyl nimbolinin（2）,were isolated from the fruits of Melia toosendan.Their...Two new limonoids,1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12α-ethoxyl nimbolinin（1） and lα-benzoyloxy-3α-acetoxyl-7α- hydroxyl-12α-ethoxyl nimbolinin（2）,were isolated from the fruits of Melia toosendan.Their structures were established on the basis of various NMR spectroscopic analyses,including 2D-NMR techniques（HSQC,HMBC,NOESY） and HR-ESI-MS.展开更多
Objective:To explore the potential mechanism of hepatotoxicity induced by Fructus Meliae Toosendan(FMT)through network pharmacology.Methods:The active components and targets of FMT were identified and screened by Trad...Objective:To explore the potential mechanism of hepatotoxicity induced by Fructus Meliae Toosendan(FMT)through network pharmacology.Methods:The active components and targets of FMT were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database,PubChem Database and Swiss Target Prediction database,etc.Genecards,pharmGKB,and OMIM databases were used to collect relevant targets of hepatotoxicity,and intersect them with the targets of active ingredients to obtain the potential targets of hepatotoxicity caused by FMT.A compound-target network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted by R software,and then the pathways directly related to hepatotoxicity were integrated.Results:In this study,9 active ingredients of FMT and 265 targets were obtained.There are 533 hepatotoxicity-related targets,and 76 potential targets for hepatotoxicity caused by FMT,among which quercetin,melianone,and nimbolin A are the key active components for hepatotoxicity caused by FMT,and MYC,STAT3,JUN,and RELA were the core target proteins of FMT’s hepatotoxicity.There were 2353 GO entries(P<0.05),including 2181 Biological Process(BP),41 Cellular Component(CC)and 131 Molecular Function(MF).KEGG enrichment analysis revealed 165 pathways(P<0.05),of which Th17 cell differentiation,HIF-1 signaling pathway,PI3K-Akt signaling pathway were strongly correlated with the hepatotoxicity of FMT.Conclusion:Through network pharmacology,it was found that many potential components in azadirachia chinaberry may be involved in the regulation of apoptosis,excessive inflammatory response and mitochondrial dynamics through multi-target and multi-pathway,resulting in the generation of hepatotoxicity.展开更多
A new method for the determination of toosendanin in the bark of Melia toosendan sieb.et zucc.by reversed-phase high performance liquid chromatography（RP-HPLC）with MeOH-H2O as the mobile phase at 215 nm of the uv-vi...A new method for the determination of toosendanin in the bark of Melia toosendan sieb.et zucc.by reversed-phase high performance liquid chromatography（RP-HPLC）with MeOH-H2O as the mobile phase at 215 nm of the uv-vis wavelength was investigated.A good seperatioin of toosendanin with matrix was obtained within 20 min by using Eclipse XDB-C8 column.The linear regression equation for peak area-toosendain concentration is A=20.818C-31,r=0.9997.展开更多
基金Supported by the Natural Science Foundation Project of Science Committee of Chongqing,China(No.CQ CSTC2009BB5258)
文摘Objective： To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo. Methods： Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography （HPLC）. Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract. Results： HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration （IC50, 72 h） was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/（kg·d）] and low-dose [0.138 mg/（kg·d）] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced. Conclusions： Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.
文摘Two new phenylpropanetriol glycosides, named as meliadanoside A (3 - methoxy- 5 - hydroxy-9- (1' - O-β-D-glucopyranosyl) - threo - phenylpropanetriol ) and meliadanoside B (4- hydroxy-7, 8- (2', 1' - O- β- D -glucopyranosyl) - phenylpropanetriol), were isolated from the water-soluble extract of the fruits of Meliatoosendan Sieb. et Zucc., along with threo-guaiacylglycerol. Their structures were elucidated by spectroscopic and chendcal analysis.
文摘Two new limonoid-type triterpenoids, named 12-o-ethyl-l-deacetylnimbolinin B and 1-o-tigloyl-1-o-debenzoylohchinal, have been isolated from the fruit of Melia toosendan Sieb. et Zucc. Their structures were elucidated by spectral methods, including 2D-NMR spectra.
文摘Two new limonoids,1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12α-ethoxyl nimbolinin（1） and lα-benzoyloxy-3α-acetoxyl-7α- hydroxyl-12α-ethoxyl nimbolinin（2）,were isolated from the fruits of Melia toosendan.Their structures were established on the basis of various NMR spectroscopic analyses,including 2D-NMR techniques（HSQC,HMBC,NOESY） and HR-ESI-MS.
基金Project supported by Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital,(No.202016)。
文摘Objective:To explore the potential mechanism of hepatotoxicity induced by Fructus Meliae Toosendan(FMT)through network pharmacology.Methods:The active components and targets of FMT were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database,PubChem Database and Swiss Target Prediction database,etc.Genecards,pharmGKB,and OMIM databases were used to collect relevant targets of hepatotoxicity,and intersect them with the targets of active ingredients to obtain the potential targets of hepatotoxicity caused by FMT.A compound-target network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted by R software,and then the pathways directly related to hepatotoxicity were integrated.Results:In this study,9 active ingredients of FMT and 265 targets were obtained.There are 533 hepatotoxicity-related targets,and 76 potential targets for hepatotoxicity caused by FMT,among which quercetin,melianone,and nimbolin A are the key active components for hepatotoxicity caused by FMT,and MYC,STAT3,JUN,and RELA were the core target proteins of FMT’s hepatotoxicity.There were 2353 GO entries(P<0.05),including 2181 Biological Process(BP),41 Cellular Component(CC)and 131 Molecular Function(MF).KEGG enrichment analysis revealed 165 pathways(P<0.05),of which Th17 cell differentiation,HIF-1 signaling pathway,PI3K-Akt signaling pathway were strongly correlated with the hepatotoxicity of FMT.Conclusion:Through network pharmacology,it was found that many potential components in azadirachia chinaberry may be involved in the regulation of apoptosis,excessive inflammatory response and mitochondrial dynamics through multi-target and multi-pathway,resulting in the generation of hepatotoxicity.
文摘A new method for the determination of toosendanin in the bark of Melia toosendan sieb.et zucc.by reversed-phase high performance liquid chromatography（RP-HPLC）with MeOH-H2O as the mobile phase at 215 nm of the uv-vis wavelength was investigated.A good seperatioin of toosendanin with matrix was obtained within 20 min by using Eclipse XDB-C8 column.The linear regression equation for peak area-toosendain concentration is A=20.818C-31,r=0.9997.
