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
Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH...Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH3CN. To better understand the struc^re-activity relationship of CAPE, phenylethyl-monobenzoylcinnamate and phenylethyl-dibenzoylcinnamate were prepared. Meanwhile, the structure of phenylethyl-monobenzoylcinnamate was confirmed by single-crystal X-ray diffiaction.展开更多
4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. ...4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC 12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.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
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
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
AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of ceruleaninduced acute pancreatitis (AP).METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute ede...AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of ceruleaninduced acute pancreatitis (AP).METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-α levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased signif icantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathologicalresults and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-α concentration was nearly the same in the CAPE and placebo groups.CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of benef icial effects of CAPE before clinical usage of this agent.展开更多
Aim： To show the oxidative stress after cigarette smoke exposure in rat testis and to evaluate the effects of caffeic acid phenethyl ester （CAPE）. Methods： Twenty-one rats were divided into three groups of seven. ...Aim： To show the oxidative stress after cigarette smoke exposure in rat testis and to evaluate the effects of caffeic acid phenethyl ester （CAPE）. Methods： Twenty-one rats were divided into three groups of seven. Animals in Group Ⅰ were used as control. Rats in Group Ⅱ were exposed to cigarette smoke only （4 × 30 min/d） and rats in Group Ⅲ were exposed to cigarette smoke and received daily intraperitoneal injections of CAPE （10 μmol/kg.d）. After 60 days all the rats were killed and the levels of nitric oxide （NO） and anti-oxidant enzymes such as superoxide-dismutase, catalase and glutathione peroxidase （GSH-Px） and the level of malondialdehyde were studied in the testicular tissues of rats with spectrophotometric analysis. Results： There was a significant increase in catalase and superoxide-dismutase activities in Group Ⅱ when compared to the controls, but the levels of both decreased after CAPE administration in Group Ⅲ. GSH-Px activity was decreased in Group Ⅱ but CAPE caused an elevation in GSH-Px activity in Group Ⅲ. The difference between the levels of GSH-Px in Group Ⅰ and Group Ⅱ was significant, but the difference between groups Ⅱ and Ⅲ was not significant. Elevation of malondialdehyde after smoke exposure was significant and CAPE caused a decrease to a level which was not statistically different to the control group. A significantly increased level of NO after exposure to smoke was reversed by CAPE administration and the difference between NO levels in groups Ⅰ and Ⅲ was statistically insignificant. Conclusion： Exposure to cigarette smoke causes changes in the oxidative enzyme levels in rat testis, but CAPE can reverse these harmful effects. （Asian J Andro12006 Mar; 8： 189-193）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 inhibiting oxidative stress.展开更多
Objective： To investigate the inhibitory effect of caffeic acid phenethyl ester（CAPE） on the proliferation of vascular smooth muscle cells （VSMC） activated by lipopolysaccharide （LPS） and to clarify its mechani...Objective： To investigate the inhibitory effect of caffeic acid phenethyl ester（CAPE） on the proliferation of vascular smooth muscle cells （VSMC） activated by lipopolysaccharide （LPS） and to clarify its mechanism. Methods： VSMC activated by LPS （1 mg-L^-1） were treated with CAPE at different concentrations. The inhibitory effecfs of CAPE on the proliferation of VSMC were determined by methabenzthiazuron（MTT） colorimetry. The effects of CAPE on the expression of proliferating cell nuclear antigen （PCNA） and Survivin protein in VSMC were evaluated by immunocytochemistry staining technique （SABC method）. Cell cycle was analyzed by flow cytometry（FCM） with propidiumiodide （PI） labeling method. The relative expression level of Survivin mRNA was measured with real-time quantified RT-PCR technique. Results. CAPE exerted significant inhibitory effects on. proliferation of VSMC at concentrations ranging from 5 mg·L^-1 to 80 mg·L^-1, decreased the rate of cells positive for PCNA and Survivin protein and repressed the expressioh of Survivin mRNA in a dose- and time-dependent manner （P 〈 0.05）. FCM analysis displayed that CAPE up-regulated the ratio of G0/G1 stages and reduced the percentage of VSMC in S stage （P 〈 0.05）. Conclusion： CAPE can significantly inhibit the proliferation of VSMC activated by LPS in a dose- and time-dependent manner, which may be carded out through regulating cell cycle and repressing the expression of PCNA and Survivin.展开更多
AIM： To study of the effect of caffeic acid phenethyl ester （CAPE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODS： Male Wistar rats were subjected to a carcinogenic treatment （CT...AIM： To study of the effect of caffeic acid phenethyl ester （CAPE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODS： Male Wistar rats were subjected to a carcinogenic treatment （CT） and sacrificed at 25^th d; altered hepatic foci （AHF） were generated efficiently. To a second group of rats a single 20 mg/kg doses of CAPE was given 12 h before initiation with CT and were sacrificed at 25^th d. We evaluated the expression of preneoplastic markers as Y-glutamyltranspeptidase （GGT） and glutathione S-transferase type pi protein （GSTp） by histochemistry, RT-PCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances （TBARS） in homogenates of liver and used Unscheduled DNA Synthesis （UDS） assay by incorporation of [^3H] thymidine （^3HdT） in primary hepatocyte cultures （PHC）. RESULTS： At 25^th d after CT CAPE reduced the observed increase of GGT^＋AHF by 84% and liver expression ofggt mRNA by 100%. In case of the GSTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine （DEN） 12 h after its administration, we detected a 68% increase of TBARS. When CAPE was administered before DEN, it completely protected from liver TBARS induction. To have an indication of the sole effect of CAPE on initiation, two carcinogens were tested in a UDS assay in PHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CAPE concentration. CONCLUSION： Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.展开更多
Caffeic acid phenethyl ester(CAPE) is a natural and rare ingredient with several biological activities, but its industrial production using lipase-catalyzed esterification of caffeic acid(CA) and 2-phenylethanol(PE) i...Caffeic acid phenethyl ester(CAPE) is a natural and rare ingredient with several biological activities, but its industrial production using lipase-catalyzed esterification of caffeic acid(CA) and 2-phenylethanol(PE) in ionic liquids(ILs) is hindered by low substrate concentrations and long reaction time. To set up a high-efficiency bioprocess for production of CAPE, a novel dimethyl sulfoxide(DMSO)–IL co-solvent system was established in this study.The 2%(by volume) DMSO–[Bmim][Tf2N] system was found to be the best medium with higher substrate solubility and conversion of CA. Under the optimum conditions, the substrate concentration of CA was raised 8-fold,the reaction time was reduced by half, and the conversion reached 96.23%. The kinetics follows a ping-pong bi-bi mechanism with inhibition by PE, with kinetic parameters as follows: Vmax= 0.89 mmol · min-1· g-1, Km,CA=42.9 mmol · L-1, Km,PE= 165.7 mmol · L-1, and Ki,PE= 146.2 mmol · L-1. The results suggest that the DMSO cosolvent effect has great potential to enhance the enzymatic synthesis efficiency of CAPE in ILs.展开更多
Enhancing the ability of fish to consume a high-carbohydrate diet(HCD)is a key focus of aquaculture research.The propolis extract,caffeic acid phenethyl ester(CAPE)has anti-inflammatory,hepatoprotective,and glycolytic...Enhancing the ability of fish to consume a high-carbohydrate diet(HCD)is a key focus of aquaculture research.The propolis extract,caffeic acid phenethyl ester(CAPE)has anti-inflammatory,hepatoprotective,and glycolytic-promoting properties,but its potential to mitigate metabolic disorders in fish fed a HCD remains uncertain.This study investigated the effects of CAPE on the adaptability and utilization of a HCD in the herbivorous grass carp(Ctenopharyngodon idellus),focusing on growth performance,tissue and organ health,and nutrient metabolism.A total of 270 grass carp with an initial body weight of 12.69±0.05 g were divided into five groups(Control,HCD,HCD+C200[200 mg/kg CAPE],HCD+C500[500 mg/kg CAPE],and HCD+C800[800 mg/kg CAPE],respectively)with three replicates per group and fed for 8 weeks.Compared with Control group,the HCD reduced the final body weight,weight gain rate,specific growth rate,protein deposition rate,and crude protein in whole body and muscle(P<0.05),and increased the feed conversion ratio,intraperitoneal fat index,and hepatosomatic index of grass carp(P<0.05),whereas the addition of CAPE reduced these adverse effects(P<0.05).Peroxisome proliferator-activated receptorγ(PPARγ)was activated by CAPE in adipose tissue(P<0.05),but not in the hepatopancreas or muscle.These changes resulted in adipocyte hyperplasia(a smaller and more uniform distribution of adipocytes)and decreased immune cell penetration and inflammation.CAPE promoted the lipolysis and fatty acidβ-oxidation in the adipose tissue,hepatopancreas,and muscle.CAPE improved glucose uptake and utilization-related gene expression in the hepatopancreas and muscle,alleviated hepatic steatosis,and promoted mammalian target of rapamycin(mtor)gene expression in muscle for grass carp on the HCD(P=0.034).The addition of CAPE to the HCD inhibited inflammatory response in the adipose tissue,hepatopancreas,and muscle,and reduced the levels of alanine aminotransferase,aspartate aminotransferase,glucose,lactic dehydrogenase,low-density lipoprotein cholesterol,and triglycerides in the serum(P<0.05).In summary,CAPE altered the pattern of adipose tissue expansion by promoting adipocyte hyperplasia,thereby promoting glucose and lipid metabolism,and ameliorated the adverse effects of a HCD on inflammation and growth performance in grass carp.展开更多
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National Natural Science Foundation of China (Grant No. 20672008, 20972011)
文摘Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH3CN. To better understand the struc^re-activity relationship of CAPE, phenylethyl-monobenzoylcinnamate and phenylethyl-dibenzoylcinnamate were prepared. Meanwhile, the structure of phenylethyl-monobenzoylcinnamate was confirmed by single-crystal X-ray diffiaction.
基金National Natural Science Foundation of China(Grant No.201310061931.8)
文摘4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC 12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.
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.
文摘AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of ceruleaninduced acute pancreatitis (AP).METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-α levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased signif icantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathologicalresults and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-α concentration was nearly the same in the CAPE and placebo groups.CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of benef icial effects of CAPE before clinical usage of this agent.
文摘Aim： To show the oxidative stress after cigarette smoke exposure in rat testis and to evaluate the effects of caffeic acid phenethyl ester （CAPE）. Methods： Twenty-one rats were divided into three groups of seven. Animals in Group Ⅰ were used as control. Rats in Group Ⅱ were exposed to cigarette smoke only （4 × 30 min/d） and rats in Group Ⅲ were exposed to cigarette smoke and received daily intraperitoneal injections of CAPE （10 μmol/kg.d）. After 60 days all the rats were killed and the levels of nitric oxide （NO） and anti-oxidant enzymes such as superoxide-dismutase, catalase and glutathione peroxidase （GSH-Px） and the level of malondialdehyde were studied in the testicular tissues of rats with spectrophotometric analysis. Results： There was a significant increase in catalase and superoxide-dismutase activities in Group Ⅱ when compared to the controls, but the levels of both decreased after CAPE administration in Group Ⅲ. GSH-Px activity was decreased in Group Ⅱ but CAPE caused an elevation in GSH-Px activity in Group Ⅲ. The difference between the levels of GSH-Px in Group Ⅰ and Group Ⅱ was significant, but the difference between groups Ⅱ and Ⅲ was not significant. Elevation of malondialdehyde after smoke exposure was significant and CAPE caused a decrease to a level which was not statistically different to the control group. A significantly increased level of NO after exposure to smoke was reversed by CAPE administration and the difference between NO levels in groups Ⅰ and Ⅲ was statistically insignificant. Conclusion： Exposure to cigarette smoke causes changes in the oxidative enzyme levels in rat testis, but CAPE can reverse these harmful effects. （Asian J Andro12006 Mar; 8： 189-193）
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 inhibiting oxidative stress.
文摘Objective： To investigate the inhibitory effect of caffeic acid phenethyl ester（CAPE） on the proliferation of vascular smooth muscle cells （VSMC） activated by lipopolysaccharide （LPS） and to clarify its mechanism. Methods： VSMC activated by LPS （1 mg-L^-1） were treated with CAPE at different concentrations. The inhibitory effecfs of CAPE on the proliferation of VSMC were determined by methabenzthiazuron（MTT） colorimetry. The effects of CAPE on the expression of proliferating cell nuclear antigen （PCNA） and Survivin protein in VSMC were evaluated by immunocytochemistry staining technique （SABC method）. Cell cycle was analyzed by flow cytometry（FCM） with propidiumiodide （PI） labeling method. The relative expression level of Survivin mRNA was measured with real-time quantified RT-PCR technique. Results. CAPE exerted significant inhibitory effects on. proliferation of VSMC at concentrations ranging from 5 mg·L^-1 to 80 mg·L^-1, decreased the rate of cells positive for PCNA and Survivin protein and repressed the expressioh of Survivin mRNA in a dose- and time-dependent manner （P 〈 0.05）. FCM analysis displayed that CAPE up-regulated the ratio of G0/G1 stages and reduced the percentage of VSMC in S stage （P 〈 0.05）. Conclusion： CAPE can significantly inhibit the proliferation of VSMC activated by LPS in a dose- and time-dependent manner, which may be carded out through regulating cell cycle and repressing the expression of PCNA and Survivin.
基金Supported by grant 31665-N from Conacyt, Mexico City, Mexico. One of us, CECL, is a recipient of a fellowship from Conacyt 1996-2001 (112857), México City, México
文摘AIM： To study of the effect of caffeic acid phenethyl ester （CAPE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODS： Male Wistar rats were subjected to a carcinogenic treatment （CT） and sacrificed at 25^th d; altered hepatic foci （AHF） were generated efficiently. To a second group of rats a single 20 mg/kg doses of CAPE was given 12 h before initiation with CT and were sacrificed at 25^th d. We evaluated the expression of preneoplastic markers as Y-glutamyltranspeptidase （GGT） and glutathione S-transferase type pi protein （GSTp） by histochemistry, RT-PCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances （TBARS） in homogenates of liver and used Unscheduled DNA Synthesis （UDS） assay by incorporation of [^3H] thymidine （^3HdT） in primary hepatocyte cultures （PHC）. RESULTS： At 25^th d after CT CAPE reduced the observed increase of GGT^＋AHF by 84% and liver expression ofggt mRNA by 100%. In case of the GSTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine （DEN） 12 h after its administration, we detected a 68% increase of TBARS. When CAPE was administered before DEN, it completely protected from liver TBARS induction. To have an indication of the sole effect of CAPE on initiation, two carcinogens were tested in a UDS assay in PHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CAPE concentration. CONCLUSION： Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.
基金Supported by the National Natural Science Foundation of China(21206061)the China Postdoctoral Science Foundation funded project(2012M510124,2013T60505)+4 种基金the Natural Science Foundation of Jiangsu Province(BK2009213)the Qing Lan Project of Jiangsu Province(2014)the Graduate Innovation Project of Jiangsu Province(CXZZ13_0713)the Graduate Innovation Project of Jiangsu University of Science and Technology(2013)the Postdoctoral Science Foundation funded project of Jiangsu University(1143002085)
文摘Caffeic acid phenethyl ester(CAPE) is a natural and rare ingredient with several biological activities, but its industrial production using lipase-catalyzed esterification of caffeic acid(CA) and 2-phenylethanol(PE) in ionic liquids(ILs) is hindered by low substrate concentrations and long reaction time. To set up a high-efficiency bioprocess for production of CAPE, a novel dimethyl sulfoxide(DMSO)–IL co-solvent system was established in this study.The 2%(by volume) DMSO–[Bmim][Tf2N] system was found to be the best medium with higher substrate solubility and conversion of CA. Under the optimum conditions, the substrate concentration of CA was raised 8-fold,the reaction time was reduced by half, and the conversion reached 96.23%. The kinetics follows a ping-pong bi-bi mechanism with inhibition by PE, with kinetic parameters as follows: Vmax= 0.89 mmol · min-1· g-1, Km,CA=42.9 mmol · L-1, Km,PE= 165.7 mmol · L-1, and Ki,PE= 146.2 mmol · L-1. The results suggest that the DMSO cosolvent effect has great potential to enhance the enzymatic synthesis efficiency of CAPE in ILs.
基金supported by the National Natural Science Foundation of China(NSFC)(32002403).
文摘Enhancing the ability of fish to consume a high-carbohydrate diet(HCD)is a key focus of aquaculture research.The propolis extract,caffeic acid phenethyl ester(CAPE)has anti-inflammatory,hepatoprotective,and glycolytic-promoting properties,but its potential to mitigate metabolic disorders in fish fed a HCD remains uncertain.This study investigated the effects of CAPE on the adaptability and utilization of a HCD in the herbivorous grass carp(Ctenopharyngodon idellus),focusing on growth performance,tissue and organ health,and nutrient metabolism.A total of 270 grass carp with an initial body weight of 12.69±0.05 g were divided into five groups(Control,HCD,HCD+C200[200 mg/kg CAPE],HCD+C500[500 mg/kg CAPE],and HCD+C800[800 mg/kg CAPE],respectively)with three replicates per group and fed for 8 weeks.Compared with Control group,the HCD reduced the final body weight,weight gain rate,specific growth rate,protein deposition rate,and crude protein in whole body and muscle(P<0.05),and increased the feed conversion ratio,intraperitoneal fat index,and hepatosomatic index of grass carp(P<0.05),whereas the addition of CAPE reduced these adverse effects(P<0.05).Peroxisome proliferator-activated receptorγ(PPARγ)was activated by CAPE in adipose tissue(P<0.05),but not in the hepatopancreas or muscle.These changes resulted in adipocyte hyperplasia(a smaller and more uniform distribution of adipocytes)and decreased immune cell penetration and inflammation.CAPE promoted the lipolysis and fatty acidβ-oxidation in the adipose tissue,hepatopancreas,and muscle.CAPE improved glucose uptake and utilization-related gene expression in the hepatopancreas and muscle,alleviated hepatic steatosis,and promoted mammalian target of rapamycin(mtor)gene expression in muscle for grass carp on the HCD(P=0.034).The addition of CAPE to the HCD inhibited inflammatory response in the adipose tissue,hepatopancreas,and muscle,and reduced the levels of alanine aminotransferase,aspartate aminotransferase,glucose,lactic dehydrogenase,low-density lipoprotein cholesterol,and triglycerides in the serum(P<0.05).In summary,CAPE altered the pattern of adipose tissue expansion by promoting adipocyte hyperplasia,thereby promoting glucose and lipid metabolism,and ameliorated the adverse effects of a HCD on inflammation and growth performance in grass carp.
