Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review.
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ABSTRACT:
SUBMITTER: Akyol S
PROVIDER: S-EPMC4065767 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.
| S-EPMC6381107 | biostudies-literature
Project description:AIM:Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. RESULTS:CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability. The CED-10(Rac-1)/PAK1 pathway was essential for immunomodulation by CAPE and was a critical component involved in the immune response to fungal pathogens. CONCLUSION:Caenorhabditis elegans is an efficient heterologous host to evaluate immunomodulatory compounds and identify components of the pathway(s) involved in the mode of action of compounds.
| S-EPMC6161127 | biostudies-literature
Project description:BackgroundSeveral studies have suggested that caffeic acid phenethyl ester (CAPE) can induce the expression of hypoxia inducible factor-1α (HIF-1α) protein. We determined whether CAPE has a novel function in improving the homing and engraftment of haematopoietic stem/progenitor cells (HSPCs) by regulating HIF-1α gene expression in the bone marrow (BM) niche.MethodsFor survival experiments, lethally irradiated C57BL/6 mice were injected with a low number of BM mononuclear cells (MNCs) and CAPE according to the indicated schedule. Homing efficiency analysis was conducted using flow cytometry and colony-forming unit (CFU) assays. The influence of intraperitoneal injection of CAPE on short-term and long-term engraftment of HSPCs was evaluated using competitive and non-competitive mouse transplantation models. To investigate the mechanism by which CAPE enhanced HSPC homing, we performed these experiments including Q-PCR, western blot, immunohistochemistry and CFU assays after in-vivo HIF-1α activity blockade.ResultsCAPE injection significantly increased the survival rate of recipient mice after lethal irradiation and transplantation of a low number of BM MNCs. Using HSPC homing assays, we found that CAPE notably increased donor HSPC homing to recipient BM. The subsequent short-term and long-term engraftment of transplanted HSPCs was also improved by the optimal schedule of CAPE administration. Mechanistically, we found that CAPE upregulated the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A) and stromal cell-derived factor 1α (SDF-1α). The HIF-1α inhibitor PX-478 blocked CAPE-enhanced HSPC homing, which supported the idea that HIF-1α is a key target of CAPE.ConclusionsOur results showed that CAPE administration facilitated HSPC homing and engraftment, and this effect was primarily dependent on HIF-1α activation and upregulation of SDF-1α and VEGF-A expression in the BM niche.
| S-EPMC5678809 | biostudies-literature
Project description:Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.
| S-EPMC4365380 | biostudies-literature
Project description:We report the elaboration of redox-responsive functional micellar nanocarriers designed for triggered release of caffeic acid phenethyl ester (CAPE) in cancer therapy. Three-layered micelles, comprising a poly(ε-caprolactone) (PCL) core, a middle poly(acrylic acid)/poly(ethylene oxide) (PAA/PEO) layer and a PEO outer corona, were prepared by co-assembly of PEO113-b-PCL35-b-PEO113 and PAA13-b-PCL35-b-PAA13 amphiphilic triblock copolymers in aqueous media. The preformed micelles were loaded with CAPE via hydrophobic interactions between the drug molecules and PCL core, and subsequently crosslinked by reaction of carboxyl groups from PAA and a disulfide crosslinking agent. The reaction of crosslinking took place in the middle layer of the nanocarriers without changing the encapsulation efficiency (EE~90%) of the system. The crosslinked polymeric micelles (CPMs) exhibited superior structural stability and did not release CAPE in phosphate buffer (pH 7.4). However, in weak acidic media and in the presence of 10 mM reducing agent (dithiothreitol, DTT), the payload was released at a high rate from CPMs due to the breakup of disulfide linkages. The physicochemical properties of the nanocarriers were investigated by dynamic and electrophoretic light scattering (DLS and ELS) and atomic force microscopy (AFM). The rapid release of CAPE under intracellular-like conditions and the lack of premature drug release in media resembling the blood stream (neutral pH) make the developed CPMs a promising candidate for controllable drug release in the microenvironment of tumors.
| S-EPMC8953340 | biostudies-literature
Project description:Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis, known for a variety of health promoting and therapeutic potentials. We investigated the molecular mechanism of anticancer and anti-metastasis activities of CAPE. cDNA array performed on the control and CAPE-treated breast cancer cells revealed activation of DNA damage signaling involving upregulation of GADD45? and p53 tumor suppressor proteins. Molecular docking analysis revealed that CAPE is capable of disrupting mortalin-p53 complexes. We provide experimental evidence and demonstrate that CAPE induced disruption of mortalin-p53 complexes led to nuclear translocation and activation of p53 resulting in growth arrest in cancer cells. Furthermore, CAPE-treated cells exhibited downregulation of mortalin and several other key regulators of cell migration accountable for its anti-metastasis activity. Of note, we found that whereas CAPE was unstable in the culture medium (as it gets degraded into caffeic acid by secreted esterases), its complex with gamma cyclodextrin (?CD) showed high efficacy in anti-tumor and anti-metastasis assays in vitro and in vivo (when administered through either intraperitoneal or oral route). The data proposes that CAPE-?CD complex is a potent anti-cancer and anti-metastasis reagent.
| S-EPMC5039358 | biostudies-literature
Project description:Caffeic acid phenethyl ester (CAPE) has been reported as a multifunctional compound. In this report, we tested the effect of CAPE and its derivatives on hepatitis C virus (HCV) replication in order to develop an effective anti-HCV compound. CAPE and CAPE derivatives exhibited anti-HCV activity against an HCV replicon cell line of genotype 1b with EC50 values in a range from 1.0 to 109.6 µM. Analyses of chemical structure and antiviral activity suggested that the length of the n-alkyl side chain and catechol moiety are responsible for the anti-HCV activity of these compounds. Caffeic acid n-octyl ester exhibited the highest anti-HCV activity among the tested derivatives with an EC50 value of 1.0 µM and an SI value of 63.1 by using the replicon cell line derived from genotype 1b strain Con1. Treatment with caffeic acid n-octyl ester inhibited HCV replication of genotype 2a at a similar level to that of genotype 1b irrespectively of interferon signaling. Caffeic acid n-octyl ester could synergistically enhance the anti-HCV activities of interferon-alpha 2b, daclatasvir, and VX-222, but neither telaprevir nor danoprevir. These results suggest that caffeic acid n-octyl ester is a potential candidate for novel anti-HCV chemotherapy drugs.
| S-EPMC3866116 | biostudies-literature
Project description:Melanoma is highly metastatic and resistant to chemotherapeutic drugs. Our previous studies have demonstrated that caffeic acid phenethyl ester (CAPE) suppresses the growth of melanoma cells and induces reactive oxygen species generation. However, the exact mechanism of the growth suppressive effects of CAPE was not clear. Here, we determined the potential mechanism of CAPE against melanoma in vivo and in vitro. Administration of 10 mg/kg/day CAPE substantially suppressed the growth of B16F0 tumor xenografts in C57BL/6 mice. Tumors from CAPE-treated mice showed reduced phosphorylation of phosphoinositide 3-kinase, AKT, mammalian target of rapamycin and protein level of X-linked inhibitor of apoptosis protein (XIAP) and enhanced the cleavage of caspase-3 and poly (ADP ribose) polymerase. In order to confirm the in vivo observations, melanoma cells were treated with CAPE. CAPE treatment suppressed the activating phosphorylation of phosphoinositide 3-kinase at Tyr 458, phosphoinositide-dependent kinase-1 at Ser 241, mammalian target of rapamycin at Ser 2448 and AKT at Ser 473 in B16F0 and SK-MEL-28 cells in a concentration and time-dependent study. Furthermore, the expression of XIAP, survivin and BCL-2 was downregulated by CAPE treatment in both cell lines. Significant apoptosis was observed by CAPE treatment as indicated by cleavage of caspase-3 and poly (ADP ribose) polymerase. AKT kinase activity was inhibited by CAPE in a concentration-dependent manner. CAPE treatment increased the nuclear translocation of XIAP, indicating increased apoptosis in melanoma cells. To confirm the involvement of reactive oxygen species in the inhibition of AKT/XIAP pathway, cells were treated with antioxidant N-acetyl-cysteine (NAC) prior to CAPE treatment. Our results indicate that NAC blocked CAPE-mediated AKT/XIAP inhibition and protected the cells from apoptosis. Because AKT regulates XIAP, their interaction was examined by immunoprecipitation studies. Our results show that CAPE treatment decreased the interaction of AKT with XIAP. To establish the involvement of AKT in the apoptosis-inducing effects of CAPE, cells were transfected with AKT. Our results revealed that AKT overexpression attenuated the decrease in XIAP and significantly blocked CAPE-mediated apoptosis. Similarly, overexpression of XIAP further decreased CAPE-induced apoptosis. Taken together, our results suggest that CAPE suppresses phosphoinositide 3-kinase/AKT/XIAP pathway leading to apoptosis in melanoma tumor cells in vitro and in vivo.
| S-EPMC3765043 | biostudies-literature
Project description:Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by progressive demyelination and disabling outcomes. CD4+ T cells are the most critical driving factor of relapsing MS, but little improvement has been noted upon deletion of the whole T cell population. Caffeic acid phenethyl ester (CAPE), one of the main active compounds of propolis, exhibits potent antitumour, anti-inflammatory, and antioxidant properties by suppressing nuclear factor-κB (NF-κB) transactivation. To investigate the therapeutic potential of CAPE in MS, we studied the effects of CAPE on cytokine levels, T cells, and NF-κB activities and in an experimental MS animal model. The results showed that cerebrospinal fluid (CSF) from patients with relapsing MS is characterized by increased levels of proinflammatory cytokines/chemokines that preferentially skew towards T helper 1 (Th1) cytokines. In vitro studies demonstrated that CAPE not only inhibited T cell proliferation and activation but also effectively modulated T cell subsets. Under both Th0- and Th1-polarizing conditions, the proportion of CD4+IFN-γ + cells was downregulated, while CD4+Foxp3+ cells were increased. Moreover, nuclear translocation of NF-κB p65 was inhibited by CAPE. In a murine experimental autoimmune encephalomyelitis model, prophylactic treatment with CAPE significantly decreased the disease incidence and severity. Compared to the vehicle group, mice pretreated with CAPE showed diminished inflammatory cell infiltration, microglia/macrophage activation, and demyelination injury. Additionally, CAPE pretreatment reduced the level of Th1 cells in both spleen and the CNS and increased regulatory T cells (Tregs) in the CNS. In conclusion, our results highlight the potential merit of CAPE in suppressing T cell activity mainly through targeting the pathogenic Th1 lineage, which may be beneficial for MS treatment.
| S-EPMC7568814 | biostudies-literature
Project description:This study investigated the effect of CAPE on planktonic growth, biofilm-forming abilities, mature biofilms, and cell death of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis strains. Our results showed a strain- and dose-dependent effect of CAPE on Candida, and the MIC values were between 12.5 and 100 µg/mL. Similarly, the MBIC values of CAPE ranging between 50 and 100 µg/mL highlighted the inhibition of the biofilm-forming abilities in a dose-dependent manner, as well. However, CAPE showed a weak to moderate biofilm eradication ability (19-49%) on different Candida strains mature biofilms. Both caspase-dependent and caspase-independent apoptosis after CAPE treatment were observed in certain tested Candida strains. Our study has displayed typical apoptotic hallmarks of CAPE-induced chromatin margination, nuclear blebs, nuclear condensation, plasma membrane detachment, enlarged lysosomes, cytoplasm fragmentation, cell wall distortion, whole-cell shrinkage, and necrosis. In conclusion, CAPE has a concentration and strain-dependent inhibitory activity on viability, biofilm formation ability, and cell death response in the different Candida species.
| S-EPMC8614700 | biostudies-literature