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PubMed2005

A novel antioxidant agent caffeic acid phenethyl ester prevents shock wave-induced renal tubular oxidative stress.

The aim of this study was to evaluate the effects of the novel free radical scavenger caffeic acid phenethyl ester (CAPE) on extracorporeal shock wave lithotripsy (ESWL) induced renal impairment. The study was performed using 30 rabbits which were divided into two groups, each exposed to 3,000 shock waves at 18 kV: (1) control group, (2) ESWL+CAPE treated group. Malodialdehyde (MDA), urine N-acetyl-beta-glucosaminidase (NAG) activity, uric acid and white cell counts were used as markers of oxidative stress. Following shock wave exposure there was a significant rise in MDA, NAG and uric acid and white cell counts. CAPE reduced the rise in MDA, NAG, uric acid and white cell counts. Thus CAPE treatment to a great extent prevented the induction of these renal changes. Our results suggest that the antioxidant capacity of the kidney tissue was reduced after ESWL treatment and that the tissue was exposed to oxidant stress. We conclude that CAPE treatment provided significant protection against ESWL induced free radical damage.

Acetylglucosaminidase↗
PubMed2003

The dietary hydroxycinnamate caffeic acid and its conjugate chlorogenic acid increase vitamin e and cholesterol concentrations in Sprague-Dawley rats.

Vegetarian diets are correlated with a reduced risk of developing cardiovascular disease and comprise a great variety of bioactive compounds, including hydroxycinnamic acid derivatives. Therefore, this study aimed to identify dietary hydroxycinnamic acid derivatives that may alter two important factors related to the development of cardiovascular disease, namely, tocopherol (T) and cholesterol (C) concentrations in the body. The effects of caffeic acid (CA), chlorogenic acid (CGA), and ferulic acid (FA) on alpha-T, gamma-T, and C levels in blood plasma, liver, and lungs were investigated after these compounds had been fed to rats for 4 weeks at concentrations of 2 g/kg in semisynthetic diets. None of the regimens affected weight gain, feed intake, or absolute weights of livers and lungs, although CA increased the liver weight relative to the body weight (P < 0.05). CA- and CGA-fed animals showed a tendency toward sparing vitamin E in all tissues, but statistical significance was obtained only for gamma-T in the liver of CA-fed animals (P < 0.005) and for alpha-T in the lungs of CGA-treated rats (P < 0.05). CGA supplementation reduced concentrations of lipids in the lung tissue (P < 0.05). CA and CGA elevated the concentrations of C in liver tissue and lipids to a similar extent, but only CA decreased the ratio of high-density lipoprotein C to total C in blood plasma (P < 0.05 for all effects). Animals eating FA showed T and C values comparable to those in the control group. In conclusion, this study demonstrates that dietary caffeic and chlorogenic acid may elevate tocopherols and cholesterol in vivo.

Administration, Oral↗
PubMedDate not supplied

The effects of the caffeic acid phenethyl ester (CAPE) on erythrocyte membrane damage after hind limb ischaemia-reperfusion.

Reactive oxygen species have been implicated in pathogenesis injury after ischaemia-reperfusion (I/R). Caffeic Acid Phenethyl Ester (CAPE), an active component of honeybee propolis extract, exhibits antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of CAPE on erythrocyte membrane damage after hind limb I/R. Rats were divided into two groups: I/R and I/R with CAPE pre-treatment. They were anaesthetized with intramuscular ketamine 100 mg kg(-1). A 4-h I/R period was performed on the right hind limb of all animals. In the CAPE-treated group, animals received CAPE 10 microm by intraperitoneal injection 1 h before the reperfusion. At the end of the reperfusion period, a midsternotomy was performed. A 5-ml blood sample was withdrawn from the ascending aorta for biochemical assays. Serum and erythrocyte membrane MDA levels were significantly lower in the CAPE-treated group when compared to the I/R group ( p = 0.001 and p<0.001, respectively). Erythrocyte membrane Na(+)-K(+) ATPases activity in the CAPE-treated group was significantly higher than the I/R group ( p<0.001). In conclusion, CAPE seems to be effective in protecting against oxidative stress. Therefore, we suggest that in order to decrease I/R injury, pre-administration of CAPE may be a promising agent for a variety of conditions associated with I/R.

Animals↗
PubMed2006

Caffeic acid derivatives production by hairy root cultures of Echinacea purpurea.

Inoculation of leaf explants of Echinacea purpurea (Moench) with Agrobacterium rhizogenes induced hairy roots with the capacity to produce biologically active caffeic acid derivatives (CADs), especially cichoric acid. The kinetics of growth, the uptake of macronutrients, and the accumulation of CADs were investigated in heterotrophically cultured hairy roots for a 50 day period. A maximum of 12.2 g L(-1) dry biomass was achieved in MS nutrients supplemented with 30 g L(-1) sucrose on day 40. The mathematical relationship between hairy root growth and conductivity was established during the exponential phase in Erlenmeyer flasks. HPLC analyses of methanolic (0.1% phosphoric acid; 70:30, v/v) extracts from hairy roots revealed the presence of important CADs: cichoric acid (19.21 mg g(-1) dry biomass), caftaric acid (3.56 mg g(-1) dry biomass), and chlorogenic acid (0.93 mg g(-1) dry biomass). These results demonstrate that biotechnological production of CADs in hairy roots of E. purpurea is possible. Furthermore, these hairy root cultures offer, for the very first time, an excellent biological model to study the biosynthetic pathway of medicinally important CADs.

Butylamines↗
PubMed2006

Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involves beta-catenin associated signaling pathway down-regulation.

AIM: To study the anti-tumor effect of caffeic acid phenethyl ester (CAPE) and the influence of CAPE on beta-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 beta-catenin, c-myc and cyclinD1. Beta-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 beta-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of beta-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 beta-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.

Animals↗
PubMed2004

Protective role of alpha-tocopherol and caffeic acid phenethyl ester on ischemia-reperfusion injury via nitric oxide and myeloperoxidase in rat kidneys.

BACKGROUND: The aim of this study was to determine the acute effects of antioxidant caffeic acid phenethyl ester (CAPE) and alpha-tocopherol (vitamin E) on nitric oxide (NO) production, neutrophil infiltration, and antioxidant enzyme activities on an in vivo model of renal ischemia-reperfusion injury. METHODS: Rats were divided into five equal groups each consisting six rats: sham operation, ischemia, ischemia-reperfusion (I/R), I/R plus CAPE, and I/R plus vitamin E groups. CAPE or vitamin E was administered intraperitoneally before reperfusion. After experimental procedure, rats were sacrificed and both ipsilateral and contralateral kidneys were removed and prepared for NO concentrations, myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) activities. RESULTS: Acute administration of vitamin E decreased NO concentrations in both ipsilateral and contralateral renal tissues compared to I/R group. SOD activity was increased in I/R and I/R + CAPE groups compared to sham operation group. The most prominent results were encountered in MPO activities, which did not change in contralateral kidneys in both ischemia and I/R groups. There was a significant decrease in ipsilateral MPO activity in ischemia group and a significant increase in I/R group compared to sham operation group. Pretreatment with intraperitoneal CAPE significantly diminished the tissue MPO activity indicating the prevention of the neutrophil sequestration into the kidney. CONCLUSION: There is a role for CAPE in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration.

Animals↗
PubMed2005

Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester.

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 microM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.

Acetylglucosaminidase↗
PubMed2005

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Prognostic value of malondialdehyde, N-acetyl-beta-D-glucosaminidase and nitric oxide determination.

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.

Acetylglucosaminidase↗
PubMed2003

Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain.

Oxygen-derived free radicals have been implicated in the pathogenesis of cerebral injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. The purpose of the present study was to investigate the effects of ischaemia and subsequent reperfusion on rat brain and to investigate the effects of two free radical scavengers, CAPE and alpha-tocopherol, on this in vivo model of cerebral injury. Ischaemia was induced by bilateral occlusion of the carotid arteries for 20 min and reperfusion was achieved by releasing the occlusion to restore the circulation for 20 min. Control rats underwent a sham operation. CAPE at 10 micromol kg(-1) or alpha-tocopherol at 25 micromol kg(-1) was administered intraperitoneally before reperfusion. Reperfusion led to significant increase in the activity of xanthine oxidase and higher malondialdehyde levels in the brain. Acute administration of both CAPE and alpha-tocopherol suppressed ischaemia-reperfusion-induced cerebral lipid peroxidation and injury, but CAPE seems to offer a better therapeutic advantage over alpha-tocopherol.

Adenosine Deaminase↗
PubMed2007

Reaction pathways involved in the mechanism of AlIII chelation with caffeic acid: catechol and carboxylic functions competition.

Density functional theory calculations on the AlIII-caffeic acid system are carried out to investigate the fixing mechanism of this metal ion to the two competing complexing sites in the ligand. This theoretical study was performed to explain the complex formation of 1:1 stoichiometry observed in aqueous medium at low pH values. Both complexation with the catechol and carboxylic functions are envisaged. The reaction pathways for the formation of these two chelates are calculated at the B3LYP/6-31G** level of theory. The complexation on the more acidic group is relatively straightforward and shows the intermediate formation of a monodentate complex followed by a chelation process. The complexation reaction pathway with the catechol function is more sophisticated, and several pathways are explored. Once more, the formation of a monodentate complex is achieved and the most favorable pathway for chelation involves the successive steps: 1) coordination of AlIII on the oxygen atom of a hydroxyl group, 2) deprotonation of this hydroxyl group, 3) ring closure with the other oxygen atom, and 4) deprotonation of the second hydroxyl. From an energetic point of view, this second pathway is more favorable. Notably the energy barrier necessary to form the chelate is lower for the catechol function than that calculated for the carboxylic group. The results of this purely theoretical study are in complete agreement with spectroscopic investigations performed on this system.

Journal Article↗
PubMed2004

Caffeic acid phenethyl ester-induced PC-3 cell apoptosis is caspase-dependent and mediated through the loss of inhibitors of apoptosis proteins.

OBJECTIVE: To investigate the effects of a novel agent, caffeic acid phethyl ester (CAPE) on nuclear factor (NF)-kappaB activation and apoptosis in the androgen-independent PC3 prostate cancer cell line. MATERIALS AND METHODS: PC-3 cells were assessed for NF-kappaB activation induced by paclitaxel and tumour necrosis factor-alpha (TNF-alpha), using a p65 enzyme-linked immunosorbent assay, with or without CAPE treatment. The corresponding apoptosis was assessed with propidium iodide DNA staining using flow cytometry. The pan-caspase inhibitor Z-VAD-FMK was used to investigate the mechanism of apoptosis. Alterations in the expression of inhibitor of apoptosis proteins (IAP), cIAP-1, cIAP-2 and XIAP, were detected using western blot analysis. RESULTS: CAPE prevented paclitaxel and TNFalpha-mediated NF-kappaB activation. Its ability to induce apoptosis in a dose-dependent manner was associated with the loss of cIAP-1, cIAP-2 and XIAP expression. Pretreatment with Z-VAD-FMK prevented CAPE-induced apoptosis and the loss of the IAPs. CONCLUSIONS: CAPE is an effective inhibitor of NF-kappaB activation in PC-3 cells, but the mechanism of apoptosis, and the corresponding loss of IAP expression, is caspase-dependent.

Apoptosis↗
PubMed2001

Arylisothiocyanate-containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase.

Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems, yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAPE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAPE. The preparation of these CAPE isothiocyanates, required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta-mercaptoethanol (beta-ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAPE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta-ME for catalytic activity. Although in these latter enzymes, CAPE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies, is that upon binding of CAPE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands.

Amino Acid Substitution↗
PubMed2005

In vivo effects of caffeic acid phenethyl ester on myocardial ischemia-reperfusion injury and apoptotic changes in rats.

Ischemia/reperfusion (I/R) has been reported to induce apoptotic cellular death in myocardium. This study tested the hypothesis that caffeic acid phenethyl ester (CAPE), one of the active components of propolis, may ameliorate myocardial apoptosis and oxidative myocardial injury. Wistar rats were divided into 4 groups: (i) sham operated, (ii) I/R, (iii) I/R+CAPE, and (iv) I/R+glutathione (GSH). CAPE (10 micromol/kg) was infused iv 10 min before occlusion of the left anterior descending coronary artery (30 min) followed by reperfusion (120 min). GSH (5 mg/kg) was infused iv after the occlusion and immediately before reperfusion. The TdT-mediated in situ nick end-labeling (TUNEL) method was used to evaluate apoptotic activity. I/R resulted in myocardial apoptosis, alterations of antioxidant status, elevation of serum creatine kinase (CK) and aspartate aminotransferase (AST) activities, evidence of lipid peroxidation, and elevated nitric oxide levels, compared to the sham-operation group. No apoptotic cells were found in the myocardial tissue of sham-operated rats. The TUNEL-positive myocardial cells averaged 60%, 30%, and 40% in the I/R, I/R+CAPE, and I/R+GSH groups, respectively. This study demonstrates that pretreatment with CAPE provides cardio-protection from I/R injury. The I/R+CAPE group showed reduced apoptosis, attenuated NO production, elevated myocardial superoxide dismutase (SOD) activity, and diminished serum CK and AST activities, compared to the I/R group.

Animals↗
PubMed2000

Testicular nitric oxide levels after unilateral testicular torsion/detorsion in rats pretreated with caffeic acid phenethyl ester.

Nitric oxide (NO) plays an important role in modulating blood flow in normal and in several pathological conditions, and its levels seem to change with ischemia-reperfusion injuries. Caffeic acid phenethyl ester (CAPE), an active component of propolis, exhibits antioxidant properties. This experimental study was designed to determine the changes in NO levels and the effect of CAPE on NO levels after testicular torsion/ detorsion in rats. Thirty-five adult male albino rats were divided into four groups: sham operation (n = 8), torsion (n = 9), saline/detorsion (n = 9), and CAPE/detorsion (n = 9). Rats in the sham operation group were killed after the testes were handled without torsion. Rats in the torsion group were killed after 720 degrees clockwise testicular torsion for 2 h. CAPE was administered 30 min before detorsion in the CAPE/detorsion group and saline was administered in the saline/detorsion group. After 4 h of testicular detorsion in both of these groups, the rats were killed and bilateral orchiectomy was performed to determine the tissue levels of NO. The level of NO in the torsion group (113.77 +/- 33.18 nmol/g protein) was significantly higher than that of the sham operation group (64.53 +/- 29.64 nmol/g protein). In the saline/detorsion group, the NO level (31.26 +/- 12.58 nmol/g protein) was significantly lower than in the torsion and sham operation groups. CAPE administration in the CAPE/detorsion group seemed to raise the NO level (72.63 +/- 23.87 nmol/g protein) above the level of the sham operation group. Contralateral testes were not affected by the torsion/detorsion processes performed on the ipsilateral testes. These results show that NO levels increase with torsion and decrease with detorsion. CAPE administration seems to increase tissue NO levels and this may be important for protecting the testes from torsion/detorsion injuries.

Animals↗
PubMed2005

Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats.

The toxicity of gentamicin (GEN) in the kidney seems to relate to the generation of reactive oxygen species (ROS). Caffeic acid phenethyl ester (CAPE) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. It has been proposed that antioxidant maintain the concentration of reduced glutathione (GSH) may restore the cellular defense mechanisms and block lipid peroxidation thus protect against the toxicity of wide variety of nephrotoxic chemicals. We investigated the effects of CAPE on GEN-induced changes in renal malondialdehyde (MDA), a lipid peroxidation product, nitric oxide (NO) generation, superoxide dismutase (SOD), catalase (CAT) activities, GSH content, blood urea nitrogen (BUN) and serum creatinine (Cr) levels. Morphological changes in the kidney were also examined. A total of 32 rats were equally divided into four groups which were: (1) control, (2) injected with intraperitoneally (i.p.) GEN, (3) injected with i.p. GEN+CAPE and (4) injected with i.p. CAPE. GEN administration to control rats increased renal MDA and NO generation but decreased SOD and CAT activities, and GSH content. CAPE administration with GEN injections caused significantly decreased MDA, NO generation and increased SOD, CAT activities and GSH content when compared with GEN alone. Serum level of BUN and Cr significantly increased as a result of nephrotoxicity. CAPE also, significantly decreased serum BUN and Cr levels. Morphological changes in the kidney due to GEN, including tubular necrosis, were evaluated qualitatively. In addition, CAPE reduced the degree of kidney tissue damage induced by GEN. Both biochemical findings and histopathological evidence showed that administration of CAPE reduced the GEN-induced kidney damage. Our results indicated that CAPE acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level. Thus, CAPE could be effectively combined with GEN treatment.

Animals↗
PubMed1996

Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells.

Topical application of caffeic acid phenethyl ester (CAPE), a constituent of the propolis of honeybee hives, to the backs of CD-1 mice previously initiated with 7,12-dimethylbenz[a]anthracene (DMBA) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion and the formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in epidermal DNA. Topical application of 5 nmol TPA twice weekly for 20 weeks to mice previously initiated with 200 nmol of DMBA resulted in 18.8 skin papillomas per mouse. Topical application of 1, 10, 100 or 3000 nmol of CAPE together with 5 nmol of TPA twice a week for 20 weeks inhibited the number of skin papillomas per mouse by 24, 30, 45 or 70%, respectively, and tumor size per mouse was decreased by 42, 66, 53 or 74%, respectively. Topical application of 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with DMBA produced an average of 12.6 HMdU residues per 10(4) normal bases in epidermal DNA. Topical application of 1, 10, 100 or 3000 nmol of CAPE with 5 nmol of TPA twice weekly for 20 weeks to DMBA-initiated mice decreased the level of HMdU in epidermal DNA by 40-93%. The in vitro addition of 1.25, 2.5, 5, 10 or 20 microM CAPE to cultured HeLa cells inhibited the synthesis of DNA by 32, 44, 66, 79 or 95%, respectively, the synthesis of RNA was inhibited by 39, 43, 58, 64 or 75%, respectively, and the synthesis of protein was inhibited by 29, 30, 37, 32 or 47%, respectively. The results indicate a potent inhibitory effect of CAPE on TPA-induced tumor promotion and TPA-induced formation of HMdU in DNA of mouse skin as well as an inhibitory effect of CAPE on the synthesis of DNA, RNA and protein in culture HeLa cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Product analysis of caffeic acid oxidation by on-line electrochemistry/electrospray ionization mass spectrometry.

On-line electrochemistry/electrospray ionization mass spectrometry (EC/ESI-MS) was developed using a microflow electrolytic cell. This technique was applied to electrochemical oxidation of caffeic acid (CAF) which is known to be a highly antioxidative agent. Effects of electrolytic potentials on ion intensities of product ions and on electrolytic currents were examined at different pHs. Dimer products were detected at electrolytic potentials of E = 0.7 V (vs. Ag/AgCl) and trimer products at 1.0 V at pH 9. Dimer products were distinguished from hydrogen-bonded complexes by MS/MS experiments. Hydrogen/deuterium exchange experiments determined the number of hydroxyl and carboxyl groups in the Dimers formed by electrolysis. The mechanism of oxidative polymerization of CAF is discussed with speculation as to the structure of the dimer product.

Antioxidants↗
PubMed2006

Effect of caffeic acid phenethyl ester on survival of axial pattern flaps in rats with ischaemia-reperfusion injuries.

Oxygen-derived free radicals have been implicated in the pathogenesis of tissue injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having potent antioxidant and anti-inflammatory properties. We evaluated the ability of CAPE applied intraperitoneally in reducing tissue injury after ischaemia-reperfusion. To investigate whether treatment with CAPE modifies the concentrations of the endogenous indices of oxidant stress, we examined its effects on a model of flap ischaemia-reperfusion injury in rats. CAPE (10 micromol/kg) was given through the peritoneum before reperfusion. CAPE given intraperitoneally had an inhibitory effect on tissue injury after ischaemia-reperfusion comparable to that of a control group. The anti-inflammatory and antioxidant properties of CAPE may contribute to its suppression of tissue injury.

Animals↗