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 partition coefficient,saturation solubility,and the interactions with SC lipids.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
Biofumigation is an environmentally friendly strategy used to control nematodes and plant diseases.The volatile oil of Zanthoxylum bungeanum has high insecticidal and antibacterial activity.However,it is not known if ...Biofumigation is an environmentally friendly strategy used to control nematodes and plant diseases.The volatile oil of Zanthoxylum bungeanum has high insecticidal and antibacterial activity.However,it is not known if the seed of Z.bungeanum is a suitable material for biofumigation to control southern root-knot nematodes(SRKN)on tomato,and how it may regulate the soil bacterial community structure.We used pot experiments in the greenhouse to determine the effects of Z.bungeanum seeds on SRKN,plant growth parameters,soil physicochemical and microbial characteristics.A total of 26 volatile components,including nematicidally active substances,were identified from Z.bungeanum seeds.Z.bungeanum seed biofumigation significantly reduced the SRKN population by 88.89%and 81.55%on the 50th and 100th day after transplanting,respectively.Compared to the control,the total soluble sugar,soluble solids,soluble protein,titratable acid,root activity and the fruit yield per tomato plant increased significantly.The content of soil alkali-hydrolyzed nitrogen,available potassium and the soil enzyme activities were also significantly increased.The soil bacterial diversity and the co-occurrence network complexity were increased by Z.bungeanum seed biofumigation.Relativelymore keystone OTUs in biofumigation soil had potential plant growth-promoting capabilities.The function of Z.bungeanum seed increasing tomato production in SRKN-infected soil depends on directly killing SRKN and improving soil properties.These results indicate that Z.bungeanum seed can be used as both a nematicide and a high quality organic fertilizer in tomato production.展开更多
In this investigation,the effects of PE,EtOAc,and BuOH fractions from Zanthoxylum bungeanum on cholesterol accumulation induced by sterols and LPS were determined in vitro and in vivo.HepG2 cells induced by 25-hydroxy...In this investigation,the effects of PE,EtOAc,and BuOH fractions from Zanthoxylum bungeanum on cholesterol accumulation induced by sterols and LPS were determined in vitro and in vivo.HepG2 cells induced by 25-hydroxychoelsterol and cholesterol were employed as cell model.After treatment with PE,EtOAC,or BuOH fractions,cellular total cholesterol and apolipoprotein B secretion were significantly reduced.In addition,compared with control group,expressions of SREBP2,HMGCR,and ACAT decreased,while CYP27A1,ABCA1,and LDLR levels increased.Cholesterol accumulation was also induced in C57BL/6 mice by LPS and the mice were used as the animal model.Determination of serum TNF-α level and hepatic mRNA expression of TNF-α,IL-6,iNOS,COX-2 revealed that EtOAc and BuOH fractions had anti-inflammatory effects.Furthermore,hepatic total cholesterol was reduced,accompanied by the elevation of LXR-α and ABCA1 gene expression in BuOH fraction treated mice.Since EtOAc and BuOH fractions were found active,bioassay-guided isolation was performed and β-sitosterol,eudesmin,sesamin and syringaresinol-β-D-glucoside were isolated from the fractions.展开更多
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
Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetra...Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine (TCM) active components. Toxicities of Z. bungeanum oil and three selected terpene compounds (terpinen-4-ol, 1,8-cineole, and limonene) in epidermal keratinocytes (HaCaT) and dermal flbroblast (CCC-ESF-1) cell lines were measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Five model drugs in TCM external preparations, namely osthole (OT), tetramethylpyrazine (TMP), ferulic acid (FA), puerarin (PR), and geniposide (GP), which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum (SC) and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared (FTIR) spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order: terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.展开更多
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 partition coefficient,saturation solubility,and the interactions with SC lipids.
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This project was supported by the Key Research and Development Program of Shandong Province(Grant No.2017GNC13104)Major Agricultural Application Technology Innovation Project of Shandong Province(2018)+1 种基金Shandong Agriculture Research System(Grant No.SDAIT-05-05)Industrial upgrading project of agricultural science of Shandong Province(2017).
文摘Biofumigation is an environmentally friendly strategy used to control nematodes and plant diseases.The volatile oil of Zanthoxylum bungeanum has high insecticidal and antibacterial activity.However,it is not known if the seed of Z.bungeanum is a suitable material for biofumigation to control southern root-knot nematodes(SRKN)on tomato,and how it may regulate the soil bacterial community structure.We used pot experiments in the greenhouse to determine the effects of Z.bungeanum seeds on SRKN,plant growth parameters,soil physicochemical and microbial characteristics.A total of 26 volatile components,including nematicidally active substances,were identified from Z.bungeanum seeds.Z.bungeanum seed biofumigation significantly reduced the SRKN population by 88.89%and 81.55%on the 50th and 100th day after transplanting,respectively.Compared to the control,the total soluble sugar,soluble solids,soluble protein,titratable acid,root activity and the fruit yield per tomato plant increased significantly.The content of soil alkali-hydrolyzed nitrogen,available potassium and the soil enzyme activities were also significantly increased.The soil bacterial diversity and the co-occurrence network complexity were increased by Z.bungeanum seed biofumigation.Relativelymore keystone OTUs in biofumigation soil had potential plant growth-promoting capabilities.The function of Z.bungeanum seed increasing tomato production in SRKN-infected soil depends on directly killing SRKN and improving soil properties.These results indicate that Z.bungeanum seed can be used as both a nematicide and a high quality organic fertilizer in tomato production.
基金National Science and Technology Major Project(Grant No. 2012ZX09501001-003)
文摘In this investigation,the effects of PE,EtOAc,and BuOH fractions from Zanthoxylum bungeanum on cholesterol accumulation induced by sterols and LPS were determined in vitro and in vivo.HepG2 cells induced by 25-hydroxychoelsterol and cholesterol were employed as cell model.After treatment with PE,EtOAC,or BuOH fractions,cellular total cholesterol and apolipoprotein B secretion were significantly reduced.In addition,compared with control group,expressions of SREBP2,HMGCR,and ACAT decreased,while CYP27A1,ABCA1,and LDLR levels increased.Cholesterol accumulation was also induced in C57BL/6 mice by LPS and the mice were used as the animal model.Determination of serum TNF-α level and hepatic mRNA expression of TNF-α,IL-6,iNOS,COX-2 revealed that EtOAc and BuOH fractions had anti-inflammatory effects.Furthermore,hepatic total cholesterol was reduced,accompanied by the elevation of LXR-α and ABCA1 gene expression in BuOH fraction treated mice.Since EtOAc and BuOH fractions were found active,bioassay-guided isolation was performed and β-sitosterol,eudesmin,sesamin and syringaresinol-β-D-glucoside were isolated from the fractions.
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supported by the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine (TCM) active components. Toxicities of Z. bungeanum oil and three selected terpene compounds (terpinen-4-ol, 1,8-cineole, and limonene) in epidermal keratinocytes (HaCaT) and dermal flbroblast (CCC-ESF-1) cell lines were measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Five model drugs in TCM external preparations, namely osthole (OT), tetramethylpyrazine (TMP), ferulic acid (FA), puerarin (PR), and geniposide (GP), which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum (SC) and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared (FTIR) spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order: terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.