Two new unsaturated alkylamides （2E,7E,9E）-N-（2-hydroxy-2-methylpropyl）-6,11-dioxo-2,7,9-dodecatrienamide （1） and （2E,6E,8E）-N-（2-hydroxy-2-methylpropyl）-10-oxo-2,6,8-decatrienamide （2） together with six k...Two new unsaturated alkylamides （2E,7E,9E）-N-（2-hydroxy-2-methylpropyl）-6,11-dioxo-2,7,9-dodecatrienamide （1） and （2E,6E,8E）-N-（2-hydroxy-2-methylpropyl）-10-oxo-2,6,8-decatrienamide （2） together with six known compounds （3-8） have been isolated from the pericarps of Zanthoxylum bungeanum. Their structures were elucidated on the basis of extensive spectroscopic analysis, including MS, IR, 1D and 2D NMR experiments.展开更多
The chemical composition of Zanthoxylum bungeanum（Z bungeanum） essential oi1（39 batches） was analyzed by gas chromatography-mass spectrometry（GC-MS） analysis（23 ingredients）, and the antitumor activity against...The chemical composition of Zanthoxylum bungeanum（Z bungeanum） essential oi1（39 batches） was analyzed by gas chromatography-mass spectrometry（GC-MS） analysis（23 ingredients）, and the antitumor activity against HeLa cells was detected via the MTT[3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide] assay. Two composition-activity relationship（CAR） models, generalized regression neural network（GRNN） and support vector regression（SVR） were respectively used to calculate the mean impact value（MIV） so as to identify bioactive com- pounds. Among them 9 ingredients（peaks 4, 15, 7, 8, 13, 3, 16, 9 and 11） were selected due to their high absolute MIVs. All of them have been confirmed with potential antitumor activity by previous researches. The CAR model combined with MIV was expected to be a credible tool for the active compound identification from herbs.展开更多
The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The...The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.展开更多
Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Meth...Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Methods:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin.Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z.bungeanum oil.The molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action.Results:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs.After treatment with Z.bungeanum oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration increased.There was no significant difference between the control and the Z.bungeanum oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased.The oxygen-containing constituents in Z.bungeanum oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide 3.Conclusion:Z.bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic drugs.The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partitio展开更多
Plant MYB transcription factors(TFs) play crucial roles in regulating the biosynthesis of flavonoids but current analysis on their role in Zanthoxylum bungeanum Maxim.(ZBM) is far from comprehensive. In this study, we...Plant MYB transcription factors(TFs) play crucial roles in regulating the biosynthesis of flavonoids but current analysis on their role in Zanthoxylum bungeanum Maxim.(ZBM) is far from comprehensive. In this study, we identified 270 MYB genes in ZBM and divided them into four subfamilies. The R2 R3-MYB(ZbMYB) category contained 251 genes and was classified into 33 subfamilies according to their phylogenetic results and sequence similarity. These subfamilies included 24 subgroups containing both MYBs of ZBM plants and AtMYBs, and nine subgroups containing only ZBM MYBs or AtMYBs. ZbMYBs with similar functions clustered into the same subgroup, indicating functional conservation. The subcellular localization analysis predicted that most ZbMYB genes were found in the nucleus. The transposed duplications appeared to play a major role in the expansion of the MYB gene family in ZBM. Through phylogenetic analysis and transcriptome profiling, it was found that 28 ZbMYB genes may regulate the biosynthesis of flavonoids in ZBM, and these genes expression presented distinct temporal and spatial expression patterns. In different fruit development stages of ZBM, the expression patterns of EVM0042160 and EVM0033809 genes obtained by qRT-PCR analysis are very similar to the flavonoid and anthocyanin content curves in ZBM. Further correlation analysis showed that the content of flavonoids in different fruit development stages and the transcript abundance levels of 28 ZbMYB genes have different degrees of correlation relationship. These results indicated that the ZbMYB genes might be involved in the flavonoid metabolic pathway. This comprehensive and systematic analysis of MYB family genes provided a solid foundation for further functional analysis of MYB TFs in ZBM.展开更多
Objective:This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli(FZ)against type 2 diabetes mellitus(T2DM)based on network pharmacology and experimental validation.Methods...Objective:This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli(FZ)against type 2 diabetes mellitus(T2DM)based on network pharmacology and experimental validation.Methods:Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry,and gas chromatography-mass spectrometry were used to identify the constituents of FZ.Next,the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases(including Gene Expression Omnibus database and Swiss Target Prediction online database),and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG).Finally,the pathway was verified by in vitro experiments,and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.Results:A total of 43 components were identified from FZ,and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM.The dug component-target network indicated that PPARA,PPARG,PIK3R3,JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM.Interestingly,the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase(AMPK)and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathways.In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in Hep G2 cells.Moreover,FZ treatment was able to promote the AMPK and PI3K/Akt expressions in Hep G2 cells.Conclusion:Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.展开更多
基金supported by the National Natural Science Foundation of China(Nos.31171695 and 21142004)the New Century Talents Scheme of the Ministry of Education(No.NCET-08-0820)the Fundamental Research Funds for Central Universities(No.SWJTU2010ZT09)
文摘Two new unsaturated alkylamides （2E,7E,9E）-N-（2-hydroxy-2-methylpropyl）-6,11-dioxo-2,7,9-dodecatrienamide （1） and （2E,6E,8E）-N-（2-hydroxy-2-methylpropyl）-10-oxo-2,6,8-decatrienamide （2） together with six known compounds （3-8） have been isolated from the pericarps of Zanthoxylum bungeanum. Their structures were elucidated on the basis of extensive spectroscopic analysis, including MS, IR, 1D and 2D NMR experiments.
基金the National Natural Science Foundation of China
文摘The chemical composition of Zanthoxylum bungeanum（Z bungeanum） essential oi1（39 batches） was analyzed by gas chromatography-mass spectrometry（GC-MS） analysis（23 ingredients）, and the antitumor activity against HeLa cells was detected via the MTT[3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide] assay. Two composition-activity relationship（CAR） models, generalized regression neural network（GRNN） and support vector regression（SVR） were respectively used to calculate the mean impact value（MIV） so as to identify bioactive com- pounds. Among them 9 ingredients（peaks 4, 15, 7, 8, 13, 3, 16, 9 and 11） were selected due to their high absolute MIVs. All of them have been confirmed with potential antitumor activity by previous researches. The CAR model combined with MIV was expected to be a credible tool for the active compound identification from herbs.
基金supported by the National Natural Science Foundation of China(No.81073059)the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.
基金National Natural Science Foundation of China(No.81473365)Postgraduate Project of Beijing University of Chinese Medicine(No.2016-JYB-XS095)The authors also thank the Innovative Research Team of Beijing University of Chinese Medicine(No.2011-CXTD-13)for its financial support.
文摘Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Methods:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin.Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z.bungeanum oil.The molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action.Results:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs.After treatment with Z.bungeanum oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration increased.There was no significant difference between the control and the Z.bungeanum oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased.The oxygen-containing constituents in Z.bungeanum oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide 3.Conclusion:Z.bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic drugs.The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partitio
基金financially supported by the National Key R&D Program of China(2018YFD1000605)the Project of Science and Technology Development Center,National Forestry and Grassland Administration,China(KJZXSA202025)。
文摘Plant MYB transcription factors(TFs) play crucial roles in regulating the biosynthesis of flavonoids but current analysis on their role in Zanthoxylum bungeanum Maxim.(ZBM) is far from comprehensive. In this study, we identified 270 MYB genes in ZBM and divided them into four subfamilies. The R2 R3-MYB(ZbMYB) category contained 251 genes and was classified into 33 subfamilies according to their phylogenetic results and sequence similarity. These subfamilies included 24 subgroups containing both MYBs of ZBM plants and AtMYBs, and nine subgroups containing only ZBM MYBs or AtMYBs. ZbMYBs with similar functions clustered into the same subgroup, indicating functional conservation. The subcellular localization analysis predicted that most ZbMYB genes were found in the nucleus. The transposed duplications appeared to play a major role in the expansion of the MYB gene family in ZBM. Through phylogenetic analysis and transcriptome profiling, it was found that 28 ZbMYB genes may regulate the biosynthesis of flavonoids in ZBM, and these genes expression presented distinct temporal and spatial expression patterns. In different fruit development stages of ZBM, the expression patterns of EVM0042160 and EVM0033809 genes obtained by qRT-PCR analysis are very similar to the flavonoid and anthocyanin content curves in ZBM. Further correlation analysis showed that the content of flavonoids in different fruit development stages and the transcript abundance levels of 28 ZbMYB genes have different degrees of correlation relationship. These results indicated that the ZbMYB genes might be involved in the flavonoid metabolic pathway. This comprehensive and systematic analysis of MYB family genes provided a solid foundation for further functional analysis of MYB TFs in ZBM.
基金supported by the Project of Sichuan Science and Technology Program(No.22NSFSC1510)the Project of State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001)。
文摘Objective:This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli(FZ)against type 2 diabetes mellitus(T2DM)based on network pharmacology and experimental validation.Methods:Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry,and gas chromatography-mass spectrometry were used to identify the constituents of FZ.Next,the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases(including Gene Expression Omnibus database and Swiss Target Prediction online database),and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG).Finally,the pathway was verified by in vitro experiments,and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.Results:A total of 43 components were identified from FZ,and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM.The dug component-target network indicated that PPARA,PPARG,PIK3R3,JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM.Interestingly,the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase(AMPK)and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathways.In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in Hep G2 cells.Moreover,FZ treatment was able to promote the AMPK and PI3K/Akt expressions in Hep G2 cells.Conclusion:Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.
