Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is...Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is designed via phenylboronic esters with improved solubility for the alleviation of uveitis.The antioxidative 4-hydroxybenzyl alcohol(HBA)and EC can be released from the macromolecular EC prodrug under the stimulation of ROS,which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model.Overall,this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS,but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.展开更多
Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effec...Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effect of Farnesyl caffeate in cell proliferation of lung carcinoma cell line (H157). Antiproliferative effect and apoptosis on H157 cell were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) and DNA fragmentation assay, respectively. Farnesyl caffeate inhibited the growth of H157 cell in dose-dependent manner. Morphological changes of nuclei by staining Hoechst 33258 and DNA fragmentation suggested that Farnesyl caffeate induced death involved in a mechanism of apoptosis. Moreover, caspase-3, caspase-7 and caspase-9 were activated by Farnesyl caffeate on H157 cell. The protein expressions of Bax and Bcl-2 were down-regulated by Farnesyl caffeate, resulting in cytochrome c release from the mitochondria. Farnesyl caffeate significantly increased the expression of p53 proteins which indicates that p53 plays a pivotal role in the initiation phase of Farnesyl caffeate-induced HepG2 cell apoptosis. These results demonstrated Farnesyl caffeate-induced apoptosis in human lung carcinoma cell line. More detailed mechanism of ?Farnesyl caffeate-induced H157 apoptosis remains to be elucidated.展开更多
The nascent polypeptide-associated complex(NAC)plays crucial roles in various biological functions in eukaryotes and has been extensively studied in animals and plants;however,its role in the biocontrol mechanisms of ...The nascent polypeptide-associated complex(NAC)plays crucial roles in various biological functions in eukaryotes and has been extensively studied in animals and plants;however,its role in the biocontrol mechanisms of microorganisms requires further investigation.This study examined the function of TbNACα,a NAC subunit,in the biocontrol activity of Trichoderma breve T069 against Sclerotium rolfsii.Following deletion of the TbNACα gene from T.breve T069,the ΔTbNACα mutant exhibited significantly reduced mycelial growth,spore production,and spore germination.While volatile substances from ΔTbNACα showed no significant effect on S.rolfsii,non-volatile substances demonstrated significant inhibition of S.rolfsii growth.Transcriptome sequencing analysis revealed 3,398 differentially expressed genes in the ΔTbNACα mutant compared to wild-type T069,primarily regulating genes associated with secondary metabolite biosynthetic enzymes,hydrolases,and membrane transport proteins.Untargeted metabolomics identified 50 upregulated metabolites(27 in positive ion mode and 23 in negative ion mode)in crude extracts from ΔTbNACα mutant metabolite broth.Among these metabolic substances,ethyl caffeate demonstrated the strongest activity against S.rolfsii,with an EC_(50) of 107.15μg mL^(-1).Quantitative real-time PCR(qPCR)analysis indicated significant upregulation of genes involved in the ethyl caffeate synthesis pathway in ΔTbNACα strains.This research establishes the negative regulation of ethyl caffeate synthesis and elucidates the antagonistic inhibition mechanism of TbNACα in T.breve T069.展开更多
Eleven compounds were isolated from Gypsophila oldhamiana and identified as octadecyl E-p-coumarate(1),octadecyl caffeate (2), ferulic acid (3), soya-cerebrosideⅠ(4), soya-cerebrosideⅡ(5), D-3-methyl-chiroinsitol (6...Eleven compounds were isolated from Gypsophila oldhamiana and identified as octadecyl E-p-coumarate(1),octadecyl caffeate (2), ferulic acid (3), soya-cerebrosideⅠ(4), soya-cerebrosideⅡ(5), D-3-methyl-chiroinsitol (6), α-spinasterol-3-O-β-D-glucopyranoside (7), α-spinasterol(8), β-sitosterol(9),daucosterol (10), sucrose (11). Compounds 1～7 were obtained from this plant for the first time; Compounds 1～3 were isolated from caryophllaceae family for the first time.展开更多
A new cafferic ester, （＋）-2-（1-hydroxyl-4-oxocyclohexyl） ethyl caffeate, was isolated from the 80% ethanol extract of the whole plants of Incarvillea mairei var. granditlora （Wehrhahn） Grierson. The structure o...A new cafferic ester, （＋）-2-（1-hydroxyl-4-oxocyclohexyl） ethyl caffeate, was isolated from the 80% ethanol extract of the whole plants of Incarvillea mairei var. granditlora （Wehrhahn） Grierson. The structure of the compound was established by spectroscopic methods.展开更多
Objective:To investigate therapeutic mechanism in Jasminum amplexicaule(Oleaceae)and verify its main active component as quality control markers Methods:Established mouse models of diarrhea,intestinal angina,and infla...Objective:To investigate therapeutic mechanism in Jasminum amplexicaule(Oleaceae)and verify its main active component as quality control markers Methods:Established mouse models of diarrhea,intestinal angina,and inflammation were firstly used to select herb fractions with optimum efficacy,followed by an in vitro experiment to determine key targets associated with effects of J.amplexicaule extract.The selected fractions were isolated and purified,its components were identified,and the obtained compounds were verified for their effects on NF-κB and i NOS.Finally,effective compounds were administered to rats,their plasma pharmacokinetic parameters were calculated,and quality markers(QMs)reflecting therapeutic activities of J.amplexicaule were confirmed.Results:Trichloromethane and ethyl acetate fractions had significant anti-diarrheal,anti-inflammatory,and analgesic effects.The trichloromethane fraction also reduced BDNF,p38 MAPK,p-p38 MAPK,NF-κB p65,and p-NF-κB p65 levels in the ileum in a rhubarb-induced diarrhea mouse model.Additionally,it inhibited LPS-induced NF-κB transcription and nitric oxide(NO)production in RAW264.7 macrophages,which suppressed i NOS expression.Therefore,the trichloromethane fraction was further investigated.QMs candidate selection identified 17 compounds,and results of in-vitro therapeutic validation indicated that methyl caffeate and isochlorogenic acid B had the strongest anti-diarrheal,anti-inflammatory,and analgesic activities.After being validated by a UHPLC–MS-MS method,concentrations of these target compounds were accurately determined in the rat plasma and pharmacokinetic parameters were calculated.Cmax,tmax,and t1/2 were respectively 575.35 ng/mL(2.963 nmol/mL),0.5 h,and 0.45 h for methyl caffeate and 262.03 ng/m L(0.5034 nmol/mL),0.25 h,and 2.03 h for isochlorogenic acid B.Because these candidate compounds exhibited favorable pharmacokinetics,they were considered as QMs of J.amplexicaule.Conclusions:The present study accurately and effectively identified QMs of J.amplexicaule that act as indicators of efficacy and quality.展开更多
基金financially supported by National Key Research and Development Project (No. 2020YFE0204400)
文摘Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is designed via phenylboronic esters with improved solubility for the alleviation of uveitis.The antioxidative 4-hydroxybenzyl alcohol(HBA)and EC can be released from the macromolecular EC prodrug under the stimulation of ROS,which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model.Overall,this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS,but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.
文摘Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effect of Farnesyl caffeate in cell proliferation of lung carcinoma cell line (H157). Antiproliferative effect and apoptosis on H157 cell were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) and DNA fragmentation assay, respectively. Farnesyl caffeate inhibited the growth of H157 cell in dose-dependent manner. Morphological changes of nuclei by staining Hoechst 33258 and DNA fragmentation suggested that Farnesyl caffeate induced death involved in a mechanism of apoptosis. Moreover, caspase-3, caspase-7 and caspase-9 were activated by Farnesyl caffeate on H157 cell. The protein expressions of Bax and Bcl-2 were down-regulated by Farnesyl caffeate, resulting in cytochrome c release from the mitochondria. Farnesyl caffeate significantly increased the expression of p53 proteins which indicates that p53 plays a pivotal role in the initiation phase of Farnesyl caffeate-induced HepG2 cell apoptosis. These results demonstrated Farnesyl caffeate-induced apoptosis in human lung carcinoma cell line. More detailed mechanism of ?Farnesyl caffeate-induced H157 apoptosis remains to be elucidated.
基金supported by the National Natural Science Foundation of China(32060589).
文摘The nascent polypeptide-associated complex(NAC)plays crucial roles in various biological functions in eukaryotes and has been extensively studied in animals and plants;however,its role in the biocontrol mechanisms of microorganisms requires further investigation.This study examined the function of TbNACα,a NAC subunit,in the biocontrol activity of Trichoderma breve T069 against Sclerotium rolfsii.Following deletion of the TbNACα gene from T.breve T069,the ΔTbNACα mutant exhibited significantly reduced mycelial growth,spore production,and spore germination.While volatile substances from ΔTbNACα showed no significant effect on S.rolfsii,non-volatile substances demonstrated significant inhibition of S.rolfsii growth.Transcriptome sequencing analysis revealed 3,398 differentially expressed genes in the ΔTbNACα mutant compared to wild-type T069,primarily regulating genes associated with secondary metabolite biosynthetic enzymes,hydrolases,and membrane transport proteins.Untargeted metabolomics identified 50 upregulated metabolites(27 in positive ion mode and 23 in negative ion mode)in crude extracts from ΔTbNACα mutant metabolite broth.Among these metabolic substances,ethyl caffeate demonstrated the strongest activity against S.rolfsii,with an EC_(50) of 107.15μg mL^(-1).Quantitative real-time PCR(qPCR)analysis indicated significant upregulation of genes involved in the ethyl caffeate synthesis pathway in ΔTbNACα strains.This research establishes the negative regulation of ethyl caffeate synthesis and elucidates the antagonistic inhibition mechanism of TbNACα in T.breve T069.
文摘Eleven compounds were isolated from Gypsophila oldhamiana and identified as octadecyl E-p-coumarate(1),octadecyl caffeate (2), ferulic acid (3), soya-cerebrosideⅠ(4), soya-cerebrosideⅡ(5), D-3-methyl-chiroinsitol (6), α-spinasterol-3-O-β-D-glucopyranoside (7), α-spinasterol(8), β-sitosterol(9),daucosterol (10), sucrose (11). Compounds 1～7 were obtained from this plant for the first time; Compounds 1～3 were isolated from caryophllaceae family for the first time.
基金program for Changjiang Scholars and Innovative Research Team in University (PCSIRT),NCET Foundation,NSFC (No.30725045)National 863 Program (No.2006AA02Z338)+1 种基金Shanghai Leading Academic Discipline Project (No.B906)the Scientific Foundation of Shanghai China (No.07DZ19728,06DZ19717,06DZ19005).
文摘A new cafferic ester, （＋）-2-（1-hydroxyl-4-oxocyclohexyl） ethyl caffeate, was isolated from the 80% ethanol extract of the whole plants of Incarvillea mairei var. granditlora （Wehrhahn） Grierson. The structure of the compound was established by spectroscopic methods.
基金the open topic grant of Guangxi Key Laboratory for TCM Quality Control Research(Gui Zhong Zhong Kai 201402)Guangxi Institute of Chinese Medicine and Pharmaceutical Science for financial support.
文摘Objective:To investigate therapeutic mechanism in Jasminum amplexicaule(Oleaceae)and verify its main active component as quality control markers Methods:Established mouse models of diarrhea,intestinal angina,and inflammation were firstly used to select herb fractions with optimum efficacy,followed by an in vitro experiment to determine key targets associated with effects of J.amplexicaule extract.The selected fractions were isolated and purified,its components were identified,and the obtained compounds were verified for their effects on NF-κB and i NOS.Finally,effective compounds were administered to rats,their plasma pharmacokinetic parameters were calculated,and quality markers(QMs)reflecting therapeutic activities of J.amplexicaule were confirmed.Results:Trichloromethane and ethyl acetate fractions had significant anti-diarrheal,anti-inflammatory,and analgesic effects.The trichloromethane fraction also reduced BDNF,p38 MAPK,p-p38 MAPK,NF-κB p65,and p-NF-κB p65 levels in the ileum in a rhubarb-induced diarrhea mouse model.Additionally,it inhibited LPS-induced NF-κB transcription and nitric oxide(NO)production in RAW264.7 macrophages,which suppressed i NOS expression.Therefore,the trichloromethane fraction was further investigated.QMs candidate selection identified 17 compounds,and results of in-vitro therapeutic validation indicated that methyl caffeate and isochlorogenic acid B had the strongest anti-diarrheal,anti-inflammatory,and analgesic activities.After being validated by a UHPLC–MS-MS method,concentrations of these target compounds were accurately determined in the rat plasma and pharmacokinetic parameters were calculated.Cmax,tmax,and t1/2 were respectively 575.35 ng/mL(2.963 nmol/mL),0.5 h,and 0.45 h for methyl caffeate and 262.03 ng/m L(0.5034 nmol/mL),0.25 h,and 2.03 h for isochlorogenic acid B.Because these candidate compounds exhibited favorable pharmacokinetics,they were considered as QMs of J.amplexicaule.Conclusions:The present study accurately and effectively identified QMs of J.amplexicaule that act as indicators of efficacy and quality.
