The cDNA fragment encoding caffeic acid 3_O_methyltransferase (COMT) in Chinese white poplar ( Populus tomentosa Carr.) was isolated and cloned by RT_PCR technique. The size of the cDNA fragment is 1 080 bp, which alm...The cDNA fragment encoding caffeic acid 3_O_methyltransferase (COMT) in Chinese white poplar ( Populus tomentosa Carr.) was isolated and cloned by RT_PCR technique. The size of the cDNA fragment is 1 080 bp, which almost covers the whole cDNA_encoding region. Authors’ cDNA fragment in P. tomentosa shares 98.7% homology with the reported corresponding cDNA in the P. tremuloids at nucleotide level, 99.4% homology at amino acid level, respectively. The analysis of Northern dot hybridization showed that COMT is expressed specifically in the developing secondary xylem of stem during the season of xylem differentiation, which means the linkage between the gene expression for a monolignol biosynthetic enzyme and seasonal regulation of xylem development in woody plant.展开更多
AIM:To study the effect of caffeic add phenethyl ester (CAPE) on proliferation, cell cycle, apoptosis and expression of β-catenin in cultured human colorectal cancer (CRC) cell line HCT116. METHODS: HCT116 cells were...AIM:To study the effect of caffeic add phenethyl ester (CAPE) on proliferation, cell cycle, apoptosis and expression of β-catenin in cultured human colorectal cancer (CRC) cell line HCT116. METHODS: HCT116 cells were treated with CAPE at serial concentrations of 80,40,20,10,5,2.5 mg/L. The proliferative status of HCT116 cells was measured by using methaben-zthiazuron (MTT) assay. Cell cycle was analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling method. The rate of apoptosis was detected by using FCM with annexin V-FITC and PI double labeling method, β-catenin levels were determined by Western blotting, β-catenin localization in HCT116 was determined by indirect immunofluorescence. RESULTS: After HCT116 cells were exposed to CAPE (80, 40, 20, 10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE (10, 5, and 2.5 mg/L) for 24 h. CAPE treatment was associated with decreased cytoplasmic β-catenin, nuclear p-catenin and a concurrent increase in β-catenin protein expression at cell-cell junctions. CONCLUSION: CAPE could inhibit HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased β-catenin protein expression may mediate the anti-proliferative effects of CAPE.展开更多
AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro a...AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively. RESULTS CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors. CONCLUSION CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.展开更多
Engineering the biosynthesis of plant-derived natural products in microbes presents several challenges, especially when the expression and activation of the plant cytochrome P450 enzyme is required. By recruiting two ...Engineering the biosynthesis of plant-derived natural products in microbes presents several challenges, especially when the expression and activation of the plant cytochrome P450 enzyme is required. By recruiting two enzymes—HpaB and HpaC—from several bacteria, we constructed functional 4- hydroxyphenylacetate 3-hydroxylase (4HPA3H) in Saccharomyces cerevisiae to take on a role similar to that of the plant-derived cytochrome P450 enzyme and produce caffeic acid. Along with a common tyrosine ammonia lyase (TAL), the different combinations of HpaB and HpaC presented varied capabilities in producing the target product, caffeic acid, from the substrate, L-tyrosine. The highest production of caffeic acid was obtained with the enzyme combination of HpaB from Pseudomonas aeruginosa and HpaC from Salmonella enterica, which yielded up to (289.4 ± 4.6) mg-L1 in shake-flask cultivation. The compatibility of heterologous enzymes within a yeast chassis was effectively improved, as the caffeic acid production was increased by 40 times from the initial yield. Six key amino acid residues around the flavin adenine dinucleotide (FAD) binding domain in HpaB from Pseudomonas aeruginosa were differentiate from those other HpaBs, and might play critical roles in affecting enzyme activity. We have thus established an effective approach to construct a highly efficient yeast system to synthesize non-native hydroxylated phenylpropanoids.展开更多
Salvianolic acid G,a caffeic acid dimer with a novel tetracyclic skeleton was isolated from the roots of Salvia miltiorrhiza.Its structure was elucidated by chemical and spectral analysis,especially by 2D NMR analysis.
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
AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester(CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to se...AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester(CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group(n = 10), a vehicle group(n = 10), a model group(n = 15), a vitamin E group(n = 10), and three CAPE groups(CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE(3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin(TBil), aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde(MDA), glutathione(GSH) levels, catalase(CAT) and superoxide dismutase(SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin(α-SMA), a characteristic hallmark of activated hepatic stellate cells(HSCs), and NF-E2-related factor 2(Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats(P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group(P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group(P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group(P < 0.01). CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by in展开更多
The effects of process variables such as enzyme types, enzyme ratio, reaction temperature, pH, time, and ethanol concentration on the extraction of unripe apple polyphenol were investigated. The results indicated that...The effects of process variables such as enzyme types, enzyme ratio, reaction temperature, pH, time, and ethanol concentration on the extraction of unripe apple polyphenol were investigated. The results indicated that Viscozyme L had the strongest effect on polyphenols extraction and was selected to study the polyphenol composition. The ratio of enzyme （Viscozyme L） to sobstrate （2 fungal beta-glucanase units （FBG）） at 0.02, reaction at pH 3.7, 50℃ for 12 h, and ethanol concentration of 70% were chosen as the most favorable extraction condition. Total phenolic content （TPC）, reducing sugar content （RSC）, and extraction yield increased by about 3, 1.5, and 2 times, respectively, compared with control. The contents ofp-coumaric acid, ferulic acid, and caffeic acid increased to 8, 4, and 32 times, respectively. The enzyme-aided polyphenol extraction process from unripe apples might be applied to food industry for enhancing bioactive compound production.展开更多
In the present work, for the first time, the main details of the electronic mechanism of the synergistic antioxidant interaction between different pairs: phenolic food acid and glutathione and the stable radical catio...In the present work, for the first time, the main details of the electronic mechanism of the synergistic antioxidant interaction between different pairs: phenolic food acid and glutathione and the stable radical cation ABTS<sup>+·</sup> were revealed on the basis of a rigorous analysis of the DFT calculated data. It was shown that among all the studied food acids, only caffeic acid exhibits a clear-cut significant synergistic effect with glutathione. It established the electronic and structural factors underlying the mechanism of the synergistic interaction of the mixture caffeic acid and glutathione in its reaction with ABTS<sup>+·</sup>. The main causes of this considered synergistic effect are, firstly, the presence of the 3-OH and 4-OH hydroxyl groups in the structure of caffeic acid, secondly, the greater stability of its anion which contains the deprotonated 4-OH hydroxyl group. All other phenolic food acids under study do not possess the given structural particularity and therefore do not show such synergistic effects with glutathione.展开更多
Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biog...Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.展开更多
OBJECTIVE:To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester(CADPE)molecule,which can prevent colorectal cancer(CRC)in the 1,2-Dimethylhydrazine(DMH)/dextran sodium sulph...OBJECTIVE:To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester(CADPE)molecule,which can prevent colorectal cancer(CRC)in the 1,2-Dimethylhydrazine(DMH)/dextran sodium sulphate(DSS)-induced mouse model.METHODS:Institute of cancer research(ICR)male mice were injected with 20 mg/kg DMH for a week.After that,2%DSS was administered in the drinking water for another 7 d.The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice.Histopathological examination was used for observing the CRC development at colonic mucosa.Immunohistochemistry(IHC),blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC.The reversing targets searching method was applied with artificial intelligence(AI),computeraided drug designing(CADD)and Ingenuity Pathway Analysis(IPA)techniques for predicting the potential targets and mechanism of CADPE highly related to CRC.RESULTS:The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment.CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development.Finally,our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor(EGFR),extracellular signal-regulated kinase(ERK)and mammalian target of rapamycin(m TOR)in two major cancer development pathways.CONCLUSIONS:CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR,ERK and m TOR activities in two highly related CRC developing pathways.展开更多
AIM： To study the anti-tumor effect of caffeic acid phenethyl ester （CAPE） and the influence of CAPE on β-catenin associated signaling pathway in SW480 colorectal cancer （CRC） cells. METHODS： SW480 cells were t...AIM： To study the anti-tumor effect of caffeic acid phenethyl ester （CAPE） and the influence of CAPE on β-catenin associated signaling pathway in SW480 colorectal cancer （CRC） cells. METHODS： SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron （MTT） assay. Cell cycle and cell apoptosis were analyzed using flow cytometry （FCM）. Western blotting assay was used to evaluate the protein level of β-catenin, c-myc and cyclinD1. β-catenin localization was determined by indirect immunofluorescence. RESULTS： CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed β-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of β-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane. CONCLUSION： CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased β-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.展开更多
In the current study,caffeic acid was an important metabolite in the highly copper-tolerant plant Elsholtzia splendens.Preparation and purification of caffeic acid were performed on the dried biomass of the plants by ...In the current study,caffeic acid was an important metabolite in the highly copper-tolerant plant Elsholtzia splendens.Preparation and purification of caffeic acid were performed on the dried biomass of the plants by means of sonication/ethanol extraction,followed by purification using a macroporous resin (D101 type) column and silica gel chromatography.The faint-yellow caffeic acid product was yielded with a purity of 98.46%,and it was chemically identified from spectra of Fourier transform infrared spectroscopy (FTIR),proton nuclear magnetic resonance (1 H NMR)/carbon nuclear magnetic resonance (13 C NMR),and electrospray ionization mass spectrometry (ESI-MS).Caffeic acid is a possible product from the post-harvest processing of Elsholtzia splendens biomass.展开更多
Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,ne...Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,nephropathy,retinopathy,cardiovascular disorders,and diabetic foot ulcers.Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications.Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase,heme oxygenase-1,superoxide dismutase,and catalase that are essential in maintaining redox balance,and ameliorate oxidative stress.Caffeic acid(CA)is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties including antioxidant,anti-inflammatory,anti-atherosclerotic,immune-stimulatory,cardioprotective,antiproliferative,and hepatoprotective activities.CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets.These include various transcription factors such as nuclear factor-B,tumor necrosis factor-α,interleukin-6,cyclooxygenase-2,and nuclear factor erythroid 2-related factor 2.Therefore,this review summarizes the pharmacological properties,molecular mechanisms,and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications.The bioavailability,drug delivery,and clinical trials of CA have also been discussed.展开更多
The title compound, （E）-4-（3-oxo-3-（（4-（N-（pyrimidin-2-yl）sulfamoyl）-phenyl）ami- no）prop- 1-en- 1-yl）- 1,2-phenylene diacetate dimethanol, was synthesized by the reaction of caffeic acid with sulfadiazine ...The title compound, （E）-4-（3-oxo-3-（（4-（N-（pyrimidin-2-yl）sulfamoyl）-phenyl）ami- no）prop- 1-en- 1-yl）- 1,2-phenylene diacetate dimethanol, was synthesized by the reaction of caffeic acid with sulfadiazine and characterized by FT-IR, 1H-NMR spectroscopy, ESI-MS and X-ray single-crystal diffraction. It crystallizes in triclinic, space group P1 with a = 10.302（7）, b = 11.621（8）, c = 12.107（8）A, a = 100.904（9）, β = 102.624（8）, y = 95.501（9）°, V= 1374.5（15）A3, Z= 2, F（000） = 588, D,= 1.354 Mg/m3, Mr = 560.57,μ= 0.176 mm-1, 2 = 0.71073 A, the final R = 0.0666 and wR = 0.1950 for 4774 observed reflections with I 〉 2σ（I）.展开更多
In this study,the protective effects of Cimicifugae Rhizoma（CR） was demonstrated in Pseudomonas aeruginosa-induced pneumonia mouse model.To identify the anti-inflammatory ingredients,an ultraperformance liquid chrom...In this study,the protective effects of Cimicifugae Rhizoma（CR） was demonstrated in Pseudomonas aeruginosa-induced pneumonia mouse model.To identify the anti-inflammatory ingredients,an ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）integrated nuclear factor κB（NF-κB） luciferase reporter assay screening system was carried out.As a result,some caffeic acid derivatives,including caffeic acid,ferulic acid/isoferulic acid,fukinolic acid,and cimicifugic acid ingredients were identified as the potential effective compounds from CR.For testing the anti-inflammatory capacity,caffeic acid was demonstrated to inhibit NF-kB and reduce the levels of IL-6 and IL-8 in TNF-α-treated BEAS-2B cells in a dose-dependent manner.Hence,CR preparations and its cinnamic acid derivatives have the possibility to be developed as a complementary therapy in the treatment of respiratory system infection in clinics.展开更多
Caffeic acid phenethyl ester(CAPE)is a rare,naturally occurring phenolic food additive.This work systematically reported fundamental data on conversion of caffeic acid(CA),yield of CAPE,and reactive selectivity during...Caffeic acid phenethyl ester(CAPE)is a rare,naturally occurring phenolic food additive.This work systematically reported fundamental data on conversion of caffeic acid(CA),yield of CAPE,and reactive selectivity during the lipase-catalyzed esterification process of CA and phenylethanol(PE)in ionic liquids(ILs).Sixteen ILs were selected as the reaction media,and the relative lipase-catalyzed synthesis properties of CAPE were measured in an effort to enhance the yield of CAPE with high selectivity.The results indicated that ILs containing weakly coordinating anions and cations with adequate alkyl chain length improved the synthesis of CAPE.[Emim][Tf2N]was selected as the optimal reaction media.The optimal parameters were as follows by response surface methodology(RSM):reaction temperature,84.0°C;mass ratio of Novozym 435 to CA,14︰1;and molar ratio of PE to CA,16︰1.The highest reactive selectivity of CAPE catalyzed by Novozym 435 in[Emim][Tf2N]reached 64.55%(CA conversion 98.76%and CAPE yield 63.75%,respectively).Thus,lipase-catalyzed esterification in ILs is a promising method suitable for CAPE production.展开更多
文摘The cDNA fragment encoding caffeic acid 3_O_methyltransferase (COMT) in Chinese white poplar ( Populus tomentosa Carr.) was isolated and cloned by RT_PCR technique. The size of the cDNA fragment is 1 080 bp, which almost covers the whole cDNA_encoding region. Authors’ cDNA fragment in P. tomentosa shares 98.7% homology with the reported corresponding cDNA in the P. tremuloids at nucleotide level, 99.4% homology at amino acid level, respectively. The analysis of Northern dot hybridization showed that COMT is expressed specifically in the developing secondary xylem of stem during the season of xylem differentiation, which means the linkage between the gene expression for a monolignol biosynthetic enzyme and seasonal regulation of xylem development in woody plant.
基金Supported by the National Natural Science Foundation of China, No. 30100228the Applied Basic Research Programs of Science and Technology Commission Foundation of Chongqing, No. 6824
文摘AIM:To study the effect of caffeic add phenethyl ester (CAPE) on proliferation, cell cycle, apoptosis and expression of β-catenin in cultured human colorectal cancer (CRC) cell line HCT116. METHODS: HCT116 cells were treated with CAPE at serial concentrations of 80,40,20,10,5,2.5 mg/L. The proliferative status of HCT116 cells was measured by using methaben-zthiazuron (MTT) assay. Cell cycle was analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling method. The rate of apoptosis was detected by using FCM with annexin V-FITC and PI double labeling method, β-catenin levels were determined by Western blotting, β-catenin localization in HCT116 was determined by indirect immunofluorescence. RESULTS: After HCT116 cells were exposed to CAPE (80, 40, 20, 10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE (10, 5, and 2.5 mg/L) for 24 h. CAPE treatment was associated with decreased cytoplasmic β-catenin, nuclear p-catenin and a concurrent increase in β-catenin protein expression at cell-cell junctions. CONCLUSION: CAPE could inhibit HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased β-catenin protein expression may mediate the anti-proliferative effects of CAPE.
基金Supported by the Liver Fibrosis Foundation of Wang BaoEn of China,No.20100033the Science and Technology Foundation of Shaanxi Province of China,No.2010K01-199
文摘AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively. RESULTS CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors. CONCLUSION CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.
基金the Ministry of Science and Technology of China (2014CB745100)the National Natural Science Foundation of China (21390203 and 21706186).
文摘Engineering the biosynthesis of plant-derived natural products in microbes presents several challenges, especially when the expression and activation of the plant cytochrome P450 enzyme is required. By recruiting two enzymes—HpaB and HpaC—from several bacteria, we constructed functional 4- hydroxyphenylacetate 3-hydroxylase (4HPA3H) in Saccharomyces cerevisiae to take on a role similar to that of the plant-derived cytochrome P450 enzyme and produce caffeic acid. Along with a common tyrosine ammonia lyase (TAL), the different combinations of HpaB and HpaC presented varied capabilities in producing the target product, caffeic acid, from the substrate, L-tyrosine. The highest production of caffeic acid was obtained with the enzyme combination of HpaB from Pseudomonas aeruginosa and HpaC from Salmonella enterica, which yielded up to (289.4 ± 4.6) mg-L1 in shake-flask cultivation. The compatibility of heterologous enzymes within a yeast chassis was effectively improved, as the caffeic acid production was increased by 40 times from the initial yield. Six key amino acid residues around the flavin adenine dinucleotide (FAD) binding domain in HpaB from Pseudomonas aeruginosa were differentiate from those other HpaBs, and might play critical roles in affecting enzyme activity. We have thus established an effective approach to construct a highly efficient yeast system to synthesize non-native hydroxylated phenylpropanoids.
文摘Salvianolic acid G,a caffeic acid dimer with a novel tetracyclic skeleton was isolated from the roots of Salvia miltiorrhiza.Its structure was elucidated by chemical and spectral analysis,especially by 2D NMR analysis.
基金Supported by National Natural Science Foundation of China No.30872466 and No.30801096the Natural Science Foundation of Chongqing No.2011BB5032PLA Logistics Science Research during the 12th Five-Year Plan Period No.BWS11J041
文摘AIM: To investigate the molecular mechanisms of the anti-cancer activity of caffeic acid phenethyl ester (CAPE).
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Liver Fibrosis Foundation of Wang Bao-En,China,No.20100033Science and Technology Foundation of Shaanxi Province,China,No.2010K01-199
文摘AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester(CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group(n = 10), a vehicle group(n = 10), a model group(n = 15), a vitamin E group(n = 10), and three CAPE groups(CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE(3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin(TBil), aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde(MDA), glutathione(GSH) levels, catalase(CAT) and superoxide dismutase(SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin(α-SMA), a characteristic hallmark of activated hepatic stellate cells(HSCs), and NF-E2-related factor 2(Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats(P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group(P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group(P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group(P < 0.01). CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by in
基金Project (No. GBTA2009-04) supported by Technology Development Program for Agriculture and Fishery, Gyeongsangbuk-Do, Korea
文摘The effects of process variables such as enzyme types, enzyme ratio, reaction temperature, pH, time, and ethanol concentration on the extraction of unripe apple polyphenol were investigated. The results indicated that Viscozyme L had the strongest effect on polyphenols extraction and was selected to study the polyphenol composition. The ratio of enzyme （Viscozyme L） to sobstrate （2 fungal beta-glucanase units （FBG）） at 0.02, reaction at pH 3.7, 50℃ for 12 h, and ethanol concentration of 70% were chosen as the most favorable extraction condition. Total phenolic content （TPC）, reducing sugar content （RSC）, and extraction yield increased by about 3, 1.5, and 2 times, respectively, compared with control. The contents ofp-coumaric acid, ferulic acid, and caffeic acid increased to 8, 4, and 32 times, respectively. The enzyme-aided polyphenol extraction process from unripe apples might be applied to food industry for enhancing bioactive compound production.
文摘In the present work, for the first time, the main details of the electronic mechanism of the synergistic antioxidant interaction between different pairs: phenolic food acid and glutathione and the stable radical cation ABTS<sup>+·</sup> were revealed on the basis of a rigorous analysis of the DFT calculated data. It was shown that among all the studied food acids, only caffeic acid exhibits a clear-cut significant synergistic effect with glutathione. It established the electronic and structural factors underlying the mechanism of the synergistic interaction of the mixture caffeic acid and glutathione in its reaction with ABTS<sup>+·</sup>. The main causes of this considered synergistic effect are, firstly, the presence of the 3-OH and 4-OH hydroxyl groups in the structure of caffeic acid, secondly, the greater stability of its anion which contains the deprotonated 4-OH hydroxyl group. All other phenolic food acids under study do not possess the given structural particularity and therefore do not show such synergistic effects with glutathione.
基金supported by pharmacy school of Chongqing Medical University.This research work was financially supported by Research Fund of Chongqing Science&Technology Commission(No:cstc2013jcyjA10040)Research Start-up Fund of Pharmacy School of Chongqing Medical University.
文摘Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.
基金National Natural Science Foundation of China Project:the Investigation of Anti-tumor Target System of Traditional Chinese Medicine(No.81274137,to Stimulate Research Targeted the Energy Metabolism Network of Tumor Cells)。
文摘OBJECTIVE:To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester(CADPE)molecule,which can prevent colorectal cancer(CRC)in the 1,2-Dimethylhydrazine(DMH)/dextran sodium sulphate(DSS)-induced mouse model.METHODS:Institute of cancer research(ICR)male mice were injected with 20 mg/kg DMH for a week.After that,2%DSS was administered in the drinking water for another 7 d.The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice.Histopathological examination was used for observing the CRC development at colonic mucosa.Immunohistochemistry(IHC),blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC.The reversing targets searching method was applied with artificial intelligence(AI),computeraided drug designing(CADD)and Ingenuity Pathway Analysis(IPA)techniques for predicting the potential targets and mechanism of CADPE highly related to CRC.RESULTS:The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment.CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development.Finally,our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor(EGFR),extracellular signal-regulated kinase(ERK)and mammalian target of rapamycin(m TOR)in two major cancer development pathways.CONCLUSIONS:CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR,ERK and m TOR activities in two highly related CRC developing pathways.
基金Supported by the National Natural Science Foundation of China, No. 30100228
文摘AIM： To study the anti-tumor effect of caffeic acid phenethyl ester （CAPE） and the influence of CAPE on β-catenin associated signaling pathway in SW480 colorectal cancer （CRC） cells. METHODS： SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron （MTT） assay. Cell cycle and cell apoptosis were analyzed using flow cytometry （FCM）. Western blotting assay was used to evaluate the protein level of β-catenin, c-myc and cyclinD1. β-catenin localization was determined by indirect immunofluorescence. RESULTS： CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed β-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of β-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane. CONCLUSION： CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased β-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.
基金Project supported by the Zhejiang Provincial Qianjiang Talents for Science and Technology (No.2011R10026)the Education Department of Zhejiang Province (No.Y201016563)+1 种基金the Research Funds from State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering (No.2009490711)the Fundamental Research Funds for the Central Universities,China
文摘In the current study,caffeic acid was an important metabolite in the highly copper-tolerant plant Elsholtzia splendens.Preparation and purification of caffeic acid were performed on the dried biomass of the plants by means of sonication/ethanol extraction,followed by purification using a macroporous resin (D101 type) column and silica gel chromatography.The faint-yellow caffeic acid product was yielded with a purity of 98.46%,and it was chemically identified from spectra of Fourier transform infrared spectroscopy (FTIR),proton nuclear magnetic resonance (1 H NMR)/carbon nuclear magnetic resonance (13 C NMR),and electrospray ionization mass spectrometry (ESI-MS).Caffeic acid is a possible product from the post-harvest processing of Elsholtzia splendens biomass.
基金financial support from University Grants Commission/Council of Scientific and Industrial Research,New Delhi,India in the form of UGC/CSIR-Senior Research Fellowships.Shiv Vardan Singh acknowledges UGC for Dr DS Kothani Fellowship.Kntika Jaiswal acknowledges financial support from University Grants Commission,New Dellhi,India in the form of UGC-CRET Fellowship.
文摘Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,nephropathy,retinopathy,cardiovascular disorders,and diabetic foot ulcers.Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications.Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase,heme oxygenase-1,superoxide dismutase,and catalase that are essential in maintaining redox balance,and ameliorate oxidative stress.Caffeic acid(CA)is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties including antioxidant,anti-inflammatory,anti-atherosclerotic,immune-stimulatory,cardioprotective,antiproliferative,and hepatoprotective activities.CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets.These include various transcription factors such as nuclear factor-B,tumor necrosis factor-α,interleukin-6,cyclooxygenase-2,and nuclear factor erythroid 2-related factor 2.Therefore,this review summarizes the pharmacological properties,molecular mechanisms,and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications.The bioavailability,drug delivery,and clinical trials of CA have also been discussed.
基金supported by the National Natural Science Foundation of China(20962002,20662001)
文摘The title compound, （E）-4-（3-oxo-3-（（4-（N-（pyrimidin-2-yl）sulfamoyl）-phenyl）ami- no）prop- 1-en- 1-yl）- 1,2-phenylene diacetate dimethanol, was synthesized by the reaction of caffeic acid with sulfadiazine and characterized by FT-IR, 1H-NMR spectroscopy, ESI-MS and X-ray single-crystal diffraction. It crystallizes in triclinic, space group P1 with a = 10.302（7）, b = 11.621（8）, c = 12.107（8）A, a = 100.904（9）, β = 102.624（8）, y = 95.501（9）°, V= 1374.5（15）A3, Z= 2, F（000） = 588, D,= 1.354 Mg/m3, Mr = 560.57,μ= 0.176 mm-1, 2 = 0.71073 A, the final R = 0.0666 and wR = 0.1950 for 4774 observed reflections with I 〉 2σ（I）.
基金financially supported by the National Natural Science Foundation of China (Nos. 81303291,81373506, 81473403)
文摘In this study,the protective effects of Cimicifugae Rhizoma（CR） was demonstrated in Pseudomonas aeruginosa-induced pneumonia mouse model.To identify the anti-inflammatory ingredients,an ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）integrated nuclear factor κB（NF-κB） luciferase reporter assay screening system was carried out.As a result,some caffeic acid derivatives,including caffeic acid,ferulic acid/isoferulic acid,fukinolic acid,and cimicifugic acid ingredients were identified as the potential effective compounds from CR.For testing the anti-inflammatory capacity,caffeic acid was demonstrated to inhibit NF-kB and reduce the levels of IL-6 and IL-8 in TNF-α-treated BEAS-2B cells in a dose-dependent manner.Hence,CR preparations and its cinnamic acid derivatives have the possibility to be developed as a complementary therapy in the treatment of respiratory system infection in clinics.
基金Supported by the Natural Science Foundation of Jiangsu Province（BK2009213） China Postdoctoral Science Foundation funded Project（2012M510124）+2 种基金 Qing Lan Project of Jiangsu Province,National Natural Science Foundation of China（21206061） Research Project of Jiangsu University of Science and Technology（35211002） Modern Agro-industry Technology Research System of China（CARS-22）
文摘Caffeic acid phenethyl ester(CAPE)is a rare,naturally occurring phenolic food additive.This work systematically reported fundamental data on conversion of caffeic acid(CA),yield of CAPE,and reactive selectivity during the lipase-catalyzed esterification process of CA and phenylethanol(PE)in ionic liquids(ILs).Sixteen ILs were selected as the reaction media,and the relative lipase-catalyzed synthesis properties of CAPE were measured in an effort to enhance the yield of CAPE with high selectivity.The results indicated that ILs containing weakly coordinating anions and cations with adequate alkyl chain length improved the synthesis of CAPE.[Emim][Tf2N]was selected as the optimal reaction media.The optimal parameters were as follows by response surface methodology(RSM):reaction temperature,84.0°C;mass ratio of Novozym 435 to CA,14︰1;and molar ratio of PE to CA,16︰1.The highest reactive selectivity of CAPE catalyzed by Novozym 435 in[Emim][Tf2N]reached 64.55%(CA conversion 98.76%and CAPE yield 63.75%,respectively).Thus,lipase-catalyzed esterification in ILs is a promising method suitable for CAPE production.
