Cestric acid,a caffeic acid ester from Cestrum euanthes

Cestric acid, a new phenolic ester was isolated from leaves of Cestrum euanthes. By means of GC, HPLC, mass spectroscopy, GC/MS, and ¹³C NMR, it was shown to be an ester of caffeic acid with glucaric acid. The ester occurs as an equilibrium mixture of four isomers.     

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.     

A new flavone glycoside from the leaves of Agastache rugosa (Fisch. & C.A.Mey.) Kuntze

Agastache rugosa (Fisch. & C.A.Mey.) Kuntze has been widely used as a food spice and a remedy for colds in Korea, China and Japan. In this study, one new flavone glycoside (1) along with six flavonoids (2–7), nine phenyl glycosides (8–16) and three megastigmane glycosides (17–19) were isolated from the leaves of A. rugosa. By extensive spectroscopic methods including 1D and 2D NMR, and MS data, the structure of the new compound (1) was elucidated as acacetin 7-O-β-(6″-(E)-crotonylglucopyranoside). From present investigation, compound 1 and 7–19 were isolated for the first time from the genus Agastache and 1, 16, 18 and 19 in the Lamiaceae family.     

Protective effects of caffeic acid phenethyl ester (CAPE) on amikacin-induced nephrotoxicity in rats

Amikacin (AK) has nephrotoxic side effects. AK-induced nephrotoxicity may be the consequence of oxidative stress and so anti-oxidant agents could be useful in reducing AK toxicity. Caffeic acid phenethyl ester (CAPE) was recently shown to have free radical scavenging ability and it reduces lipid peroxidation. For this purpose, the rats were distributed into three groups: (I) injected with vehicle (control); (II) injected (i.p.) with 1.2 g kg(-1) AK at a single dose; (III) injected (i.p.) with AK plus 10 micromol kg(-1) CAPE. Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN) and creatinine (Cr) levels. MDA production was found to be higher in rats given AK than among control rats. CAPE administration before AK injection caused a significant decrease in MDA production. Morphological tubule damage in rats given AK was severe in the renal cortex, whereas in rats given AK plus CAPE, no histological changes occurred. It is concluded that CAPE could be useful for reducing the nephrotoxic effects of AK. Copyright (c) 2005 John Wiley & Sons, Ltd.     

Teupolin III,a furanoid diterpene from Teucrium polium

A new clerodane derivative was isolated from Teucrium polium var. polium. The structure and stereochemistry have been established by detailed studies of the ¹H NMR spectra.     

Interaction between caffeic acid phenethyl ester and protease: monitoring by spectroscopic and molecular docking approaches

The interaction of one anticancer drug (caffeic acid phenethyl ester; CAPE) with three proteases (trypsin, pepsin and α-chymotrypsin) has been investigated with multispectral methods and molecular docking. As an active components in propolis, the findings are of great benefit to metabolism, design, and structural modification of drugs. The results show that CAPE has an obvious ability to quench the trypsin, pepsin, or α-chymotrypsin fluorescence mainly through a static quenching procedure. Trypsin has the largest binding affinity to CAPE, and α-chymotrypsin has the smallest binding affinity to CAPE. The data obtained from thermodynamic parameters and molecular docking prove that the spontaneously interaction between CAPE and each protease is mainly due to a combination of van der Waals (vdW) force and hydrogen bond (H-bond), controlled by an enthalpy-driven process. The binding force, strength, position, and the number of H-bond are further obtained from the results of molecular docking. Through ultraviolet spectroscopy, dynamic light scattering and circular dichroism experiments, the change in the protease secondary structure induced by CAPE was observed. Additionally, the addition of protease had a positive effect on the antioxidative activity of CAPE, and α-chymotrypsin has the greatest effect on the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals by CAPE.     

Effect of caffeic acid phenethyl ester on treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis endophthalmitis in a rabbit model

This study investigated the anti-inflammatory effects of caffeic acid phenethyl ester (CAPE), a natural bee-produced compound, and compared it with corticosteroids in the treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis (MRSE) endophthalmitis in addition to intravitreal antibiotics. An experimental endophthalmitis model was produced in 24 New Zealand albino rabbits by unilateral intravitreal injection of 0.1 ml of 4.7 x 10(4) colony-forming units (CFU) methicillin-resistant S. epidermidis. The animals were then divided randomly into three treatment groups and a control group, group 1 (six rabbits), received only intravitreal vancomycin (1.0 mg/0.1 ml); group 2 (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and intravitreal dexamethasone (400 microg/0.1 ml) and group 3 (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and subtenon CAPE (10 mg/0.3 ml) after 24 h post-infection. No treatment was given to the control group. Treatment efficacy was assessed by clinical examination, vitreous culture and histopathology. There were no statististically significant differences between clinical scores of all groups in examinations at 24 and 48 h post-infection (p = 0.915 and p = 0.067 respectively), but in examinations at 72 h post-infection and after 7 days post-infection, although the clinical scores of treatment groups were not significantly different from each other, they were significantly lower than the control group (p < 0.05). The culture results of all groups were sterile. As a result, CAPE was found to be as effective as dexamethasone in reducing inflammation in the treatment of experimental MRSE endophthalmitis when used with antibiotics. More studies are needed to determine the optimal administration route and effective dosage of this compound.     

A sugar ester and an iridoid glycoside from Scrophularia ningpoensis

From cytotoxic extracts of the roots of Scrophularia ningpoensis Hemsl. (Scrophulariaceae) a new sugar ester, ningposide D (3-O-acetyl-2-O-p-methoxycinnamoyl-alpha(beta)-L-rhamnopyranose) (1) and a new iridoid glycoside, scrophuloside B4 (6-O-(2'-O-acetyl-3'-O-cinnamoyl-4'-O-p-methoxycinnamoyl-alpha-L-rhamnopyranosyl) catalpol) (2) along with known compounds: oleanonic acid (3), ursolonic acid (4), cinnamic acid (5), 3-hydroxy-4-methoxy benzoic acid (6), 5-(hydroxymethyl)-2-furfural (7) and beta-sitosterol (8) were isolated. The structures of the new compounds were elucidated by spectral data (1, 2D NMR, EI, HRESI-MS and MS/MS). Oleanonic acid (3) and ursolonic acid (4) were found to be cytotoxic against a series of human cancer cell lines with IC50=4.6, 15.5 microM on MCF7; 4.2, 14.5 microM on K562; 14.8, 44.4 microM on Bowes; 24.9, 43.6 microM on T24S; 61.3, 151.5 microM on A549, respectively. Beta-sitosterol (8) inhibited Bowes cells growth at IC50=36.5 microM. Scrophuloside B4 (2) showed activity on K562 and Bowes cells at IC50=44.6, 90.2 microM, respectively.     

Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity. Several studies suggest that supplementation with an antioxidant can influence cisplatin-induced hepatotoxicity. The present study was designed to determine the effects of cisplatin on the liver oxidant/antioxidant system, and the possible protective effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by cisplatin. Twenty-four adult female Wistar albino rats were divided into four groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin and CAPE were injected intraperitoneally. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the other three groups. XO activity was lower in the cisplatin group than the control group. MPO activity was also increased in the cisplatin group compared to the control and CAPE groups. It can be concluded that CAPE may prevent cisplatin-induced oxidative changes in liver by strengthening the antioxidant defence system by reducing reactive oxygen species and increasing antioxidant enzyme activities.     

Taraxacoside,a type of acylated γ-butyrolactone glycoside from taraxacum officinale

In addition to the four new sesquiterpene lactones previously identified, a new acylated γ-butyrolactone glucoside, taraxacoside, was isolated from the roots of Taraxacum officinale. Its structure was elucidated mainly by ¹H and ¹³C NMR studies as β-O-[4-O-(p-hydroxyphenylacetyl]β-D-glucopyranosyl]-β-hydroxy-γ-butyrolactone. This seems to be the first instance of the detection of a monocyclic five-membered, saturated lactone O-glycoside. Additionally, p-hydroxyphenylacetic acid was identified for the first time as an acylating acid in a sugar ester.     

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat

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-β-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.     

The protective effects of caffeic acid phenethyl ester (CAPE) against liver damage induced by cigarette smoke inhalation in rats

The aim of this study was to investigate the histological and biochemical changes in liver of rats exposed to cigarette smoke and effects of caffeic acid phenetyl ester (CAPE) on these changes. For this purpose, 21 male Wistar rats were divided into three groups. Animals in Group I were used as control. Rats in Group II were exposed to cigarette smoke and rats in Group III were exposed to cigarette smoke and injected daily with CAPE. At the end of the 60-days experimental period, all rats were killed by decapitation and blood samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin levels and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px ), malondialdehyde (MDA) contents were determined. Following routine histological procedures, liver tissue specimens were examined under a light microscope. The levels of ALT, AST, total bilirubin, SOD, GSH-Px and MDA were significantly increased in rats exposed to cigarette smoke compared with those of the controls. Light microscopic examination of liver specimens from rats exposed to cigarette smoke revealed mononuclear cell infiltration and that some of the hepatocytes had a hyperchromatic nucleus and enlarged sinusoids. The rats which were treated with CAPE along with cigarettes had partially attenuated histological changes associated with cigarette exposure. In conclusion, the damage inflicted by cigarette in the rat liver can be partially prevented by CAPE administration.     

Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats

There is a great evidence that reactive oxygen species (ROS) play an important role in the pathophysiology of ischemia −reperfusion(I/R)injury in skeletal muscle.Caffeic acid phenethyl ester(CAPE)is a component of honeybeep ropolis.It has antioxidant, anti−inflammatory and free radical scavenger properties.The aim of this study is to determine the protective effects of CAPE against I/R injury in respect of protein oxidation, neutrophil in filtration, and the activities of xanthine oxidase(XO)and adenosine deaminase(AD)onan<invivomodel of skeletal muscle I/R injury.Rats were divided into three equal groups each consisting of sixrats:Sham operation, I/R, and I/R plus CAPE(I/R+CAPE)groups.CAPE was administered intraperitoneally 60 min before the beginning of the reperfusion.At the end of experimental procedure, blood and gastrocnemius muscle tissues were used for biochemical analyses.Tissue protein carbonyl(PC)levels and the activities of XO, myeloperoxidase(MPO) and AD in I/R group were significantly higher than that of control(p0.01, p0.05, p0.01, p0.005, respectively).Administration of CAPE significantly decreased tissue PC levels, MPO and XO activities in skeletal muscle compared to I/R group(p0.01, p0.05, p0.05, respectively).In addition, plasma creatine phosphokinase(CPK), XO and ADactivities were decreased in I/R+CAPE group compared to I/R group(p0.05, p0.05, p0.001). The results of this study revealed that free radical attacks may play an important role in the pathogenesis of skeletal muscle I/R injury. Also, the potent free radical scavenger compound, CAPE, may have protective potential in this process. Therefore, it can be speculated that CAPE or other antioxidant agents may be useful in the treatment of I/R injury as well as diffused traumatic injury of skeletal muscle.     

A new secoiridoid glycoside and a new sesquiterpenoid glycoside from Valeriana jatamansi with neuroprotective activity

A new secoiridoid glycoside, isopatrinioside (1) and a new sesquiterpenoid glycoside, valeriananoid F (2), together with nine known compounds, were isolated from the roots of Valeriana jatamansi. Their structures were elucidated on the basis of spectroscopic analysis. Compound 1 was an unusual monocyclic iridoid glycoside ring-opened between C-1 and C-2 produced by the cleavage of the pyran ring. Of the eleven isolates, compounds 1 and 4 exhibited moderate neuroprotective effects against CoCl₂-induced neuronal cell death in PC12 cells.     

Differential regulation of c-Jun N-terminal kinase and NF-kappaB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells

Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor κB (NF-κB) and subsequent anti-inflammatory activity. In this study, we report that (i) CAPE exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF-κB inhibition by two distinct molecular mechanisms in a cell-specific manner: CAPE inhibited downstream pathways of inhibitor κB (IκB) degradation in monocytic cells, while activation of upstream IκB kinase was suppressed by CAPE pre-treatment in astroglial cells; and (ii) CAPE paradoxically activates the c-Jun N-terminal kinase (JNK) pathway, which might be responsible for its pro-apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand-8.     

A pregnane ester glycoside from Periploca calophylla

A new pregnane ester genin, plocigenin, and a new pregnane ester diglycoside, plocin, have been isolated from the dried twigs of Periploca calophylla. The chemical and spectroscopic properties are consistent with the structures 12,20-di-O-benzoyl drevogenin-D and 12,20-di-O-benzoyl drevogenin-D-3-O-β-D-oleandropyranosyl (1 → 4)-O-β-oleandropyranoside, respectively.     

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 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-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.     

A pregnane ester diglycoside from Sarcostemma brevistigma

A pregnane ester diglycoside, brevinine, has been isolated from the dried twigs of Sarcostemma brevistigma. Its chemical and spectroscopic data are consistent with the structure 11-O-benzoyl-sarcogenin-3-O-α-L-diginopyranosyl-(1 → 4)-α-L-diginopyranoside.     

Protective effects of melatonin and caffeic acid phenethyl ester against retinal oxidative stress in long-term use of mobile phone: A comparative study

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the efficacy of the protective effects of melatonin and CAPE against retinal oxidative stress due to long-term exposure to 900 MHz EMR emitting mobile phones. Melatonin and CAPE were administered daily for 60 days to the rats prior to their EMR exposure during our study. Nitric oxide (NO, an oxidant product) levels and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of retinal oxidative stress in rats following to use of EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in retinal tissue. Retinal levels of NO and MDA increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of NO and MDA. Likewise, retinal SOD, GSH-Px and CAT activities decreased in EMR exposed animals while melatonin and CAPE caused a significant increase in the activities of these antioxidant enzymes. Treatment of EMR exposed rats with melatonin or CAPE increased the activities of SOD, GSH-Px and CAT to higher levels than those of control rats. In conclusion, melatonin and CAPE reduce retinal oxidative stress after long-term exposure to 900 MHz emitting mobile phone. Nevertheless, there was no statistically significant difference between the efficacies of these two antioxidants against to EMR induced oxidative stress in rat retina. The difference was in only GSH-Px activity in rat retina. Melatonin stimulated the retinal GSH-Px activity more efficiently than CAPE did.