Inhibitory Effect Of Ellagic Acid Research Articles

Controlled Formation of Pyrazines: Inhibition by Ellagic Acid Interaction with N-(1-Deoxy-d-xylulos-1-yl)-glycine and Promotion through Ellagic Acid Oxidation.

The effect of ellagic acid on the formation of pyrazine, methylpyrazine, 2,3-methylpyrazine, 2,6-methylpyrazine, 2,5-methylpyrazine, and trimethylpyrazine in the xylose-glycine Maillard reaction model was researched. Ellagic acid could either inhibit or promote pyrazine formation, depending on its addition time point and the pH of the system. The addition of ellagic acid during the accumulation period of an Amadori compound inhibited pyrazine formation by capturing the Amadori compound in the xylose-glycine Maillard system and decreasing the pyrazine precursors. The inhibitory effect of ellagic acid on pyrazine formation got more obvious with an increase in the pH of the system. However, when ellagic acid was added at the beginning of the xylose and glycine Maillard system and when the oxidizing substances such as glyoxal and methylglyoxal were significantly formed in the Maillard system, its oxidation could promote the formation of pyrazines.

Ellagic acid can act as a chaperone and suppress the heat-induced amyloid-like aggregation of ovalbumin

Ovalbumin (OVA) is the most abundant protein component present in egg white which has a well-balanced amino acid composition and can be used as an excellent protein source for many food products. The amyloid-like aggregation of ovalbumin induced by heating has been described by previous works, which influences its functional properties and should be avoided especially for beverages industry. The present work investigated the specific interaction between ellagic acid (EA) and ovalbumin by fluorescence quenching and molecular docking methods. The binding of ellagic acid to ovalbumin could suppress the heat-induced amyloid-like aggregation detected by thioflavin T (ThT) binding assays. Compared with the heat-induced amyloid-like aggregates of ovalbumin, the exposed hydrophobic interface of ellagic acid-bound ovalbumin after heating was significantly reduced as probed by 1-anilinonaphthalene-8-sulfonate (ANS) fluorescence. We further studied the particle size distribution and morphology of the heated ovalbumin with or without ellagic acid by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results showed that the heated ovalbumin formed large amyloid-like aggregates with an average size of approximately 660 nm, whereas the heated ovalbumin with ellagic acid at a molar ratio 1:30 maintained a soluble multimer structure with a hydrodynamic diameter of approximately 35 nm. In summary, this work reported the inhibitory effect of ellagic acid on the heat-induced amyloid-like aggregation of ovalbumin, which might provide some useful information for ovalbumin-related processing.

Ellagic acid microspheres restrict the growth of Babesia and Theileria in vitro and Babesia microti in vivo

BackgroundThere are no effective vaccines against Babesia and Theileria parasites; therefore, therapy depends heavily on antiprotozoal drugs. Treatment options for piroplasmosis are limited; thus, the need for new antiprotozoal agents is becoming increasingly urgent. Ellagic acid (EA) is a polyphenol found in various plant products and has antioxidant, antibacterial and effective antimalarial activity in vitro and in vivo without toxicity. The present study documents the efficacy of EA and EA-loaded nanoparticles (EA-NPs) on the growth of Babesia and Theileria.MethodsIn this study, the inhibitory effect of EA, β-cyclodextrin ellagic acid (β-CD EA) and antisolvent precipitation with a syringe pump prepared ellagic acid (APSP EA) was evaluated on four Babesia species and Theileria equi in vitro, and on the multiplication of B. microti in mice. The cytotoxicity assay was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3) and human foreskin fibroblast (HFF) cell lines.ResultsThe half-maximal inhibitory concentration (IC50) values of EA and β-CD EA on B. bovis, B. bigemina, B. divergens, B. caballi and T. equi were 9.58 ± 1.47, 7.87 ± 5.8, 5.41 ± 2.8, 3.29 ± 0.42 and 7.46 ± 0.6 µM and 8.8 ± 0.53, 18.9 ± 0.025, 11 ± 0.37, 4.4 ± 0.6 and 9.1 ± 1.72 µM, respectively. The IC50 values of APSP EA on B. bovis, B. bigemina, B. divergens, B. caballi and T. equi were 4.2 ± 0.42, 9.6 ± 0.6, 2.6 ± 1.47, 0.92 ± 5.8 and 7.3 ± 0.54 µM, respectively. A toxicity assay showed that EA, β-CD EA and APSP EA affected the viability of cells with a half-maximal effective concentration (EC50) higher than 800 µM. In the experiments on mice, APSP EA at a concentration of 70 mg/kg reduced the peak parasitemia of B. microti by 68.1%. Furthermore, the APSP EA-atovaquone (AQ) combination showed a higher chemotherapeutic effect than that of APSP EA monotherapy.ConclusionsTo our knowledge, this is the first study to demonstrate the in vitro and in vivo antibabesial action of EA-NPs and thus supports the use of nanoparticles as an alternative antiparasitic agent.

Photoelectrochemical determination of the activity of protein kinase A by using g-C3N4 and CdS quantum dots.

A sensitive and selective photoelectrochemical (PEC) method is described for the detection of protein kinase A (PKA) activity based on the use of graphite-like carbon nitride (g-C3N4) and the CdS quantum dots (QDs). Firstly, a complex was synthesized from g-C3N4 and gold nanoparticles (AuNPs). It was employed as both the PEC-active material and as a support for immobilization of peptides. The latter were assembled on an ITO electrode modified with g-C3N4-AuNPs and subsequently phosphorylated by PKA in the presence of adenosine 5'-[γ-thio]triphosphate (ATP-S). Finally, CdS quantum dots (QDs) were introduced on the ITO in order to increase the PEC response of g-C3N4 based on the Cd-S binding between the QDs and thiol groups. Under the optimal conditions and a typical working voltage of -0.3V, the method has a dynamic range that extends from 0.05 to 50 unit·mL-1, with a 0.017 unit·mL-1 lower detection limit. The method was successfully applied to the quantification of the inhibitory effect of ellagic acid on the activity of PKA, and to monitor enzyme activity in cell lysates. Graphical abstract Schematic of a sensitive and selective photoelectrochemical biosensor for the detection of protein kinase A activity. It is based on the use of graphite-like carbon nitride and CdS quantum dots.

Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum

BackgroundPunica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells.MethodsThe compounds ellagic acid, gallic acid and punicalagin A&B were isolated from EtOAc by high performance liquid chromatography (HPLC) and further identified by mass spectrometry (MS). The inhibitory effect of ellagic acid, gallic acid and punicalagin A&B were evaluated on the production of LPS-induced NO by Griess reagent, PGE-2 and IL-6 by immunoassay kit and prostaglandin E2 competitive ELISA kit, and COX-2 by Western blotting.ResultsEllagic acid, gallic acid and punicalagin A&B potentially inhibited LPS-induced NO, PGE-2 and IL-6 production.ConclusionThe results indicate that ellagic acid, gallic acid and punicalagin may be the compounds responsible for the anti-inflammatory potential of P. granatum.

Chemopreventive effects of ellagic acid against genotoxicity induced by benzo(a)pyrene

Benzo(a)pyrene (B(a)P) is a commonly used indicator for polycyclic aromatic hydrocarbons (PAHs) contamination. The use of certain phytochemicals and some polyphenolic compounds proved to be effective in blocking PAH-induced effects. The aim of the present study was to examine the possible inhibitory effects of ellagic acid (EA), present in berries and nuts, against B(a)P-mediated toxicity using in vitro and in vivo test systems. In vitro method included the Ames test, using Salmonella typhimurium tester strain TA100. In vivo experiments were based on mouse bone marrow micronucleus (MN) assay and immunoblotting. EA produced a decrease in the number of revertant colonies against B(a)P in the Ames assay. Further, there was a reduction in the mean number of micronucleated polychromatic erythrocytes in the presence of EA in the co-treatment protocol of the MN test. Western blotting results showed downregulation of CYP450 isoform CYP1A1 which prevented bioactivation of B(a)P. Thus, the present study demonstrates antimutagenic role played by EA against the mutagenic activity of B(a)P in both in vitro and in vivo systems.

In vivo, In vitro anti-arthritic studies of Ellagic acid from Kirganelia reticulata Baill and its molecular docking

Article history: Kirganelia reticulata is a useful shrub having various medicinal properties. In vivo, in vitro and in silico antiarthritic activity of a phytoconstituent, ellagic acid (EA) isolated from the leaves of K. reticulata was screened. EA is a naturally occurring plant polyphenol found at high concentrations that act as potential protectors against variety of human diseases. Formaldehyde induced paw edema, assumed to be one of the most suitable test procedures to screen chronic anti-inflammatory agents as it closely resembles human arthritis, and was employed for this study. The course of treatment was followed for over and 4 weeks post inoculation period using health, clinical and behavioural methods of study. Estimation of change in body weight was considered as health parameters and clinical observations included paw edema volume, change in the movements was studied in behavioural observations. The effect of EA was compared with standard drug aspirin. Various in vitro models such as inhibition of protein denaturation, effect of membrane stabilization and proteinase inhibitory actions were studied. EA with two different concentrations (100 µg/ml and 250 µg/ml) was used and results were compared with acetyl salicylic acid. Hypoxia-inducible factor (HIF-2α) promotes degradative pathways that foster osteoarthritis. The inhibitory effect of EA was studied using automated docking and efficiency was compared with standard drug in terms of interaction and binding. The isolated compound EA showed anti-arthritic activity which was found to be significant to that of the standard drugs and supports the traditional use of plant for rheumatism.

The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

Ellagic acid (EA) is able to inhibit the growth of several cancer cells; however, its effect on human ovarian carcinoma cells has not yet been investigated. Ovarian carcinoma ES-2 and PA-1 cells were treated with EA (10~100 μM) and assessed for viability, cell cycle, apoptosis, anoikis, autophagy, and chemosensitivity to doxorubicin and their molecular mechanisms. EA inhibited cell proliferation in a dose- and time-dependent manner by arresting both cell lines at the G1 phase of the cell cycle, which were from elevating p53 and Cip1/p21 and decreasing cyclin D1 and E levels. EA also induced caspase-3-mediated apoptosis by increasing the Bax : Bcl-2 ratio and restored anoikis in both cell lines. The enhancement of apoptosis and/or inhibition of autophagy in these cells by EA assisted the chemotherapy efficacy. The results indicated that EA is a potential novel chemoprevention and treatment assistant agent for human ovarian carcinoma.

Ellagic acid inhibits lipopolysaccharide-induced expression of enzymes involved in the synthesis of prostaglandin E2in human monocytes

Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has in recent years been the subject of intense research within the fields of cancer and inflammation. Pain, fever and swelling, all typical symptoms of inflammation, are ascribed to elevated levels of PGE2. In the present study, we have investigated the effects of ellagic acid on PGE2 release and on prostaglandin-synthesising enzymes in human monocytes. Ellagic acid was found to inhibit Ca ionophore A23187-, phorbol myristate acetate- and opsonised zymosan-induced release of PGE2 from monocytes pre-treated with the inflammatory agent lipopolysaccharide. Ellagic acid suppressed the lipopolysaccharide-induced increase in protein expression of cyclo-oxygenase-2 (COX-2), microsomal PGE synthase-1 (mPGEs-1) and cytosolic phospholipase A2alpha (cPLA2alpha), while it had no effect on the constitutively expressed COX-1 protein. Ellagic acid had no apparent inhibitory effect on these enzymes when the activities were determined in cell-free assays. We conclude that the inhibitory effect of ellagic acid on PGE2 release from monocytes is due to a suppressed expression of COX-2, mPGEs-1 and cPLA2alpha, rather than a direct effect on the activities of these enzymes.

Ellagic Acid Attenuates Immunoglobulin E-Mediated Allergic Response in Mast Cells

Ellagic acid is known to have anti-oxidant, anti-carcinogenic and anti-mutagenic effects. However, roles of ellagic acid in the immediate-type allergic reactions have not yet been investigated. In the present study, we have demonstrated that ellagic acid attenuates immunoglobulin (Ig)E-mediated allergic response in mast cells and in vivo. Oral administration of ellagic acid inhibited anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. Ellagic acid dose-dependently reduced histamine release and the expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in rat peritoneal mast cells (RPMC) activated by anti-DNP IgE. Moreover, ellagic acid suppressed an increase in intracellular calcium ion concentration ([Ca(2+)](i)) in RPMC. Furthermore, ellagic acid decreased the activation of nuclear factor-kappa B (NF-kappaB). Decreased NF-kappaB activity as well as reduced [Ca(2+)](i) might be involved in the inhibitory effect of ellagic acid on the secretory response. Our findings provide possibility that ellagic acid may serve as an effective therapeutic agent for allergic diseases.

Inhibitory effects of ellagic acid on the direct-acting mutagenicity of aflatoxin B 1 in the Salmonella microsuspension assay

Ellagic acid (EA) is a phenolic compound that exhibits both antimutagenic and anticarcinogenic activity in a wide range of assays in vitro and in vivo. It occurs naturally in some foods such as strawberries, raspberries, and grapes. In the previous work, we used the Salmonella microsuspension assay to examine the antimutagenicity of EA against the potent mutagen aflatoxin B 1 (AFB 1) using tester strains TA98 and TA100. Briefly, the microsuspension assay was approximately 10 times more sensitive than the standard Salmonella/microsome (Ames) test in detecting AFB 1 mutagenicity, and EA significantly inhibited mutagenicity of all AFB 1 doses in both tester strains with the addition of S9. The greatest inhibitory effect of EA on AFB 1 mutagenicity occurred when EA and AFB 1 were incubated together (with metabolic enzymes). Lower inhibition was apparent when the cells were first incubated with EA followed by a second incubation with AFB 1, or when the cells were first incubated with AFB 1 followed by a second incubation with EA alone, all with metabolic enzymes. The result of these sequential incubation studies indicates that one mechanism of inhibition could involve the formation of an AFB 1-EA chemical complex. In the present study, we further examine the effect of EA on AFB 1 mutagenicity, but without the addition of exogenous metabolic enzymes. We report the mutagenicity of AFB 1 in the microsuspension assay using TA98 and TA100 without the addition of S9. Neither the concentrations of AFB 1 (0.6, 1.2, and 2.4 μg/tube) nor the concentrations of EA (0.3, 1.5, 3, 10, and 20 μg/tube) were toxic to the bacteria. The results indicate that AFB 1 is a direct-acting mutagen, and that EA inhibits AFB 1 direct-acting mutagenicity.

Antimutagenicity of ellagic acid towards the food mutagen IQ: Investigation into possible mechanisms of action

The ability of the plant phenol ellagic acid to inhibit the mutagenicity of the food mutagen IQ was evaluated using Salmonella typhimurium strain TA98 in the Ames mutagenicity test. Ellagic acid caused a concentration-dependent decrease in the S-9- and microsome-mediated mutagenicity of IQ. The plant phenol did not interact directly with the IQ-derived mutagenic species and did not modify the cytosol-mediated activation of the promutagen. At the concentrations used in the mutagenicity studies, ellagic acid failed to inhibit microsomal mixed-function oxidase activity, including that mediated by the P450I family responsible for the bioactivation of IQ, despite being an essentially planar molecule as indicated by computer-graphic analysis. The inhibitory effect of ellagic acid was independent of its ability to chelate Mg 2+. However, pre-incubation of ellagic acid with the bacteria, followed by removal of the plant phenol, did not completely prevent the inhibitory effect of the phenol on the mutagenicity of IQ. Intraperitoneal administration of ellagic acid to rats caused a decrease in total cytochrome P-450 levels and related activities as well as in cytosolic glutathione S-transferase activity. Finally, the possibility that the reported anticarcinogenic action of ellagic acid reflects nothing more than non-selective destruction of hepatic cytochromes P-450, and thus reduced chemical activation, is considered.

Inhibitory Effects of Ellagic Acid on Glucosyltransferases from Mutans Streptococci.

Ellagic acid and its derivatives were found to abrogate the enzymatic activity of the glucosyltransferases (GTases) of mutans streptococci. These compounds preferentially inhibited the water-soluble glucan synthesis by GTase of Streptococcus mutans MT8148 and inhibited the water-insoluble glucan synthesis by GTase of Streptococcus sobrinus 6715. This inhibition resulted in a reduction of cellular adherence of mutans streptococci to a glass surface.

Inhibitory effect of ellagic acid on N-2-fluorenylacetamide-induced liver carcinogenesis in male ACI/N rats.

The effect of ellagic acid (EA) on the hepatocarcinogenesis induced by N‐2‐fluorenylacetamide (FAA) was investigated in male ACI/N rats. Rats were fed diet containing 200 ppm FAA and 400 ppm EA for 16 weeks, and diet containing 400 ppm EA alone was fed to the animals for one week before FAA exposure and one week after the carcinogen treatment. Animals were killed at intervals up to 20 weeks after cessation of the carcinogen. Liver altered foci and neoplasms were quantified using γ‐glutamyl transpeptidase reaction as well as conventional staining for identification. Exposure to FAA alone induced a substantial number of altered foci and at the end of experiment (week 36), the incidence of hepatocellular neoplasms was 100%. In the group receiving EA together with FAA, the number of altered foci was decreased at all time points and at termination, the final incidence of hepatocellular neoplasms (30%) was also reduced. Thus, EA inhibited the hepatocarcinogenesis induced by FAA when it was administered concurrently with the carcinogen.

Inhibitory effects of ellagic acid on genotoxicity induced by N-nitroso compounds

Inhibitory effects of ellagic acid on genotoxicity induced by N-nitroso compounds