Doses Of Ellagic Acid Research Articles

Investigating the Protective Effect of Ellagic Acid on Cholemic Nephropathy in Cholestatic Rats

Background: Cholemic nephropathy (CN), a renal dysfunction caused by bile acids, is a severe complication of chronic liver damage and bile duct ligation (BDL), which may lead to complete kidney failure. Objectives: This study investigated the protective effect of ellagic acid on CN in cholestatic rats. Methods: Sixty male Wistar rats weighing about 180 - 200 g were randomly divided into 6 groups for in vivo investigation. The rats were randomly divided into 5 groups of 10. Cholestasis was induced in rats by closing the bile ducts; then, the animals were treated with different doses of ellagic acid (10, 25, and 50 mg/kg). Then, the induction effect of cholestasis and the protective effects of ellagic acid on serum and urinary factors, oxidative stress indices, and histopathological changes in liver and kidney tissue were investigated. Results: Bile duct ligation in rats led to an increase in serum and urinary factors. It was also associated with increased reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) oxide form, decrease in antioxidant systems, GSH and severe histopathological changes, and fibrosis of the liver and kidney tissues. Another finding of this research was the beneficial effect of ellagic acid in improving serum and urinary factors, oxidative stress indices, and histopathological changes. Conclusions: Due to its antioxidant properties, ellagic acid can potentially serve as a novel therapeutic approach for treating kidney damage caused by increased serum levels of bile acids.

Renal protection by ellagic acid in a rat model of glycerol-induced acute kidney injury.

Studies conducted on animal models have shown that the administration of glycerol can lead to kidney tissue damage and impaired renal function. This is believed to be caused by oxidative stress and inflammation, which in turn can result in elevated levels of blood urea nitrogen (BUN) and creatinine. These metabolites are commonly used as indicators of renal function. The aim of the current experimental research was to investigate the protective efficacy of ellagic acid in a rat model of rhabdomyolysis induced by glycerol. Sixty healthy adult male Wistar rats weighing between 250 - 300 g were divided into five equal groups including control, rhabdomyolysis (administered 8.00 mL kg-1 of glycerol), and three rhabdomyolysis plus various doses of ellagic acid (25.00, 50.00 and 100 mg kg-1 per day; 72 hr after receiving glycerol for 14 days successively) groups. Serum levels of BUN, creatinine, lactate dehydrogenase, alkaline phosphatase, electrolytes and inflammatory cytokines were evaluated in all rats. Histopathological studies were also performed on kidney tissues from all groups. The administration of ellagic acid resulted in a significant increase in renal function biomarkers compared to the rats with acute kidney injury. This increase was consistent with notable reductions in tumor necrosis factor-α levels and increases in interleukin-10 levels observed in blood samples. Furthermore, the improvement in histopathological indices observed in rats received ellagic acid confirmed its nephroprotective role. The results of the current experimental study suggest that ellagic acid can improve kidney damage following glycerol injection, potentially by modulating the inflammatory process.

ELAJİK ASİDİN İNSAN KOLON KANSERİ HÜCRELERİNDE İNCELENMESİ

Cancer is seen as one of the most important and deadly diseases of our time. Colon cancer, which is one of the cancer types and ranks second in cancer-related deaths, is the second most common cancer type in men and the fourth most common cancer type in women. Ellagic acid is a plant phytochemical that can be obtained from fruits and vegetables such as strawberries, raspberries, and hazelnuts and is very important for human health. In order to understand the effects of ellagic acid on human colon cancer, different doses of ellagic acid were applied. In the proliferation study, ellagic acid was applied to CCL-233 cells at concentrations of 5 µM, 10 µM, 25 µM, 50 µM and 100 µM. Cell death was observed with an increase in applied ellagic acid concentration. The semi-lethal dose (LD50) was determined to be 40 µM. For PARP and VEGF studies, different doses of ellagic acid were applied to human colon cancer cells, which consequently showed a decrease in both values.

Ellagic Acid Prevented Dextran-Sodium-Sulfate-Induced Colitis, Liver, and Brain Injury through Gut Microbiome Changes.

Inflammatory bowel disease (IBD) affects millions of people worldwide and is considered a significant risk factor for colorectal cancer. Recent in vivo and in vitro studies reported that ellagic acid (EA) exhibits important antioxidant and anti-inflammatory properties. In this study, we investigated the preventive effects of EA against dextran sulfate sodium (DSS)-induced acute colitis, liver, and brain injury in mice through the gut-liver-brain axis. Acute colitis, liver, and brain injury were induced by treatment with 5% (w/v) DSS in the drinking water for 7 days. Freshly prepared EA (60 mg/kg/day) was orally administered, while control (CON) group mice were treated similarly by daily oral administrations with a vehicle (water). All the mice were euthanized 24 h after the final treatment with EA. The blood, liver, colon, and brain samples were collected for further histological and biochemical analyses. Co-treatment with a physiologically relevant dose (60 mg/kg/day) of EA for 7 days significantly reduced the DSS-induced gut barrier dysfunction; endotoxemia; and inflammatory gut, liver, and brain injury in mice by modulating gut microbiota composition and inhibiting the elevated oxidative and nitrative stress marker proteins. Our results further demonstrated that the preventive effect of EA on the DSS-induced IBD mouse model was mediated by blocking the NF-κB and mitogen-activated protein kinase (MAPK) pathway. Therefore, EA co-treatment significantly attenuated the pro-inflammatory and oxidative stress markers by suppressing the activation of NF-κB/MAPK pathways in gut, liver, and brain injury. These results suggest that EA, effective in attenuating IBD in a mouse model, deserves further consideration as a potential therapeutic for the treatment of inflammatory diseases.

The Nephroprotective Effects of Hibiscus sabdariffa Leaf and Ellagic Acid in Vitro and in Vivo Models of Hyperuricemic Nephropathy

Hyperuricemic nephropathy (HN) is caused by urate crystals that get deposited in the kidney and contribute to renal fibrosis. Uric acid (UA) has been proven to directly cause renal mesangial cell oxidative stress and fibrosis in the pathogenesis of HN. Some antioxidants can be used as chemopreventive agents of HN. Hibiscus sabdariffa leaf extracts (HLE), rich in polyphenol, have been shown to possess hypoglycemic, antioxidant, hypolipidemic, antiatherosclerotic, and anticancer effects. The aim of the study is to examine the inhibitory effect of HLE and its main component ellagic acid (EA) on renal fibrosis. In vitro, mouse renal glomerular mesangial SV40MES13 cells pretreated with UA were demonstrated to trigger obvious morphological changes and viability loss, as well as affect matrix metalloproteinases (MMPs) activities. Noncytotoxic doses of HLE and EA abolished the UA-induced cell injury and MMP-2/9 secretion. In addition, HLE and EA exhibited antioxidant and anti-inflammatory effects on the UA-treated cells with a reduction in transforming growth factor-beta (TGF-β) production. Next, the UA-activated pro-fibrotic factors, extracellular matrix (ECM) deposition, and epithelial-mesenchymal-transition (EMT) were inhibited by HLE or EA. Mechanistic assays indicated that antifibrotic effects of HLE might be mediated via TGF-β/Smad signaling, as confirmed by the transfection of Smad7 siRNA. In vivo, HLE and EA supplementations significantly alleviated HN development, which may result from inhibiting adenine-induced TGF-β production accompanying oxidative stress and inflammation, as well as fibrogenesis. Our data imply that EA-enriched HLE regulates the TGF-β/Smad signaling, which in turn led to reduced renal mesangial cell injury and fibrosis in HN and provided a new mechanism for its nephroprotective activity.

Anti-inflammatory effects of ellagic acid and vanillic acid against quinolinic acid-induced rat model of Huntington's disease by targeting IKK-NF-κB pathway

Huntington disease (HD), an autosomal dominant neurodegenerative disorder characterized by involuntary choreatic movements with cognitive and behavioral disturbances. HD striatum has increased conversion of kynurenine to quinolinic acid (QA) which activates NMDA receptors leading to activation of microglia and increased levels of nuclear factor kappa B (NF-κB) leading to elevated transcription of inducible nitric oxide synthase (iNOS) and various cytokines causing neuronal death via neuroinflammation, oxidative stress, mitochondrial dysfunction and apoptosis. Therefore, inhibiting IKK-NF-κB pathway induced excitotoxicity, oxidative stress and neuroinflammation could be a potential intervention in slowing down the disease progression. QA injection intrastriatally (IS-QA) produce damage mimicking HD where neuroinflammation, oxidative stress and mitochondrial dysfunction play crucial role. Ellagic acid (EA) and vanillic acid (VA) are well reported to possess antioxidant and NF-κB inhibiting effect. Hence, in present study, rats administered IS-QA were treated with EA and VA for 21 days to explore their neuroprotective effects. Behavioral studies, biochemical estimations for oxidative stress and acetylcholinesterase assay were performed. Mitochondrial function was determined by estimating mitochondrial enzyme complexes; inflammatory markers like TNF-α, IL-6, NF-κB by ELISA and apoptosis by caspase-3 levels. Brain damage was determined by histopathology which revealed their neuroprotective effects. Various doses of EA and VA produced improved motor and cognitive functions, oxidative stress and neuroinflammation were also reduced and mitochondrial functioning was improved. In a nutshell, these results signify improved motor and cognitive functions by EA and VA in QA model of HD, along with declined oxidative stress, mitochondrial dysfunction and neuroinflammation.

Dietary supplementation ellagic acid on the growth, intestinal immune response, microbiota, and inflammation in weaned piglets.

Piglets are susceptible to weaning stress, which weakens the barrier and immune function of the intestinal mucosa, causes inflammation, and ultimately affects animal growth and development. Ellagic acid (EA) is a natural polyphenol dilactone with various biological functions. However, The mechanisms underlying the effects of EA on animal health are still poorly known. Herein, we examined whether dietary supplementation with EA has a positive effect on growth performance, intestinal health, immune response, microbiota, or inflammation in weaned piglets. Sixty weaned piglets (age, 30 days) were randomly divided into two groups: the control group (basic diet) and the test group (basic diet + 500 g/t EA). The pigs were fed for 40 days under the same feeding and management conditions, and the growth performance of each individual was measured. At the end of the feeding period, samples were collected from the small intestinal mucosa for further analysis. Using these tissues, the transcriptome sequences and intestinal microbial diversity were analyzed in both groups. An inflammation model using small intestinal mucosal epithelial cells (IPEC-J2) was also constructed. Dietary EA supplementation significantly increased the average daily weight gain (ADG) and reduced diarrhea rate and serum diamine oxidase (DAO) levels of weaned piglets. Transcriptome sequencing results revealed 401 differentially expressed genes in the jejunum mucosal tissue of pigs in the control and test groups. Of these, 163 genes were up-regulated and 238 were down-regulated. The down-regulated genes were significantly enriched in 10 pathways (false discovery rate < 0.05), including seven pathways related to immune response. The results of bacterial 16s rDNA sequencing show that EA affects the composition of the intestinal microbiota in the cecum and rectum, and reveal significant differences in the abundances of Prevotella_9, Lactobacillus delbrueckii, and Lactobacillus reuteri between the test and control groups (P < 0.05). Experiments using the inflammation model showed that certain doses of EA promote the proliferation of IPEC-J2 cells, increase the relative mRNA expression levels of tight junction-related proteins (ZO-1 and Occludin), improve the compactness of the intestine, reduce the expression of inflammatory factors TNF-α and IL-6, and significantly reduce LPS-induced inflammation in IPEC-J2 cells. In conclusion, we found for the first time that dietary supplementation of EA affects the gut immune response and promotes the beneficial gut microbiota in weaned piglets, reduces the occurrence of inflammatory responses, and thereby promotes the growth and intestinal health of piglets.

The Role of the NMDA Receptor in the Anticonvulsant Effect of Ellagic Acid in Pentylenetetrazole-Induced Seizures in Male Mice.

Methods In this experimental study, 64 mice were divided into 8 groups and received the following: normal saline; EA at doses of 6.25, 12.5, and 25 mg/kg; NMDA agonist at a dose of 75 mg/kg; NMDA antagonist (ketamine) at a dose of 0.5 mg/kg; an effective dose of EA plus NMDA agonist; and a subeffective dose of EA plus ketamine. We induced seizure using intravenous administration of PTZ. 60 minutes before induction of seizure, drugs were administrated. Duration lasts to seizure-induced was measured. Finally, the gene expression of NMDA receptor subunits (Nr2a and Nr2b) was assessed in the prefrontal cortex. Results Results showed that EA increased the seizure threshold and decreased the expression of Nr2a and Nr2b. We determined that ketamine potentiated and NMDA attenuated the effects of subeffective and effective doses of EA. Conclusion EA probably via attenuation of the NMDA-R pathway possesses an anticonvulsant effect in PTZ-induced seizure in mice.

Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress.

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.

Ellagic acid restored lead-induced nephrotoxicity by anti-inflammatory, anti-apoptotic and free radical scavenging activities

Introductionlong-term environmental and occupational exposure to lead, which is a ubiquitous industrial pollutant, causes significant damage to tissues of kidney. This report aims to address this debilitating issue. A natural polyphenolic compound, Ellagic acid (EA) is having numerous potential medicinal properties. In this present study nephroprotective effects of EA has been evaluated in a rodent model with lead-induced toxicity. MethodsRats were treated with EA doses of 50 mg/kg and 25 mg/kg and simultaneously co-administered with lead acetate (60 mg/kg) for 2 months through oral route. The extent to which EA treatment provides nephroprotective effect was estimated by measurement of serum biomarkers, tissue antioxidants, inflammatory mediators, apoptosis, autophagy pathway and histological examination. ResultsEA treatment caused significant restoration in the level of serum biomarkers, tissue antioxidants and histological architecture of renal tissue. Treatment with either of the doses of EA causes restoration of pro-inflammatory mediators to approximately pre-exposure concentration. This phenomena is caused by suppression of expression levels of inflammatory molecules like tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β), as well as functional expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it was also observed that EA suppressed apoptotic and autophagic pathway by reduction of expression of light chain 3B (LC3B) level which are the oxidative DNA damage markers of renal tissue. ConclusionIt can be safely concluded that EA provides protection against lead-induced nephrotoxicity to a significant degree.

Kemoterapi Kaynaklı Hepatotoksisiteye Karşı Ellajik Asitin Koruyucu Etkileri

Aim: Cyclophosphamide (CP) is a commonly used chemotherapeutic agent despite its toxic adverse effects, including hepatotoxicity. Ellagic acid (EA) is an antioxidant agent and exhibits free radical scavenging activities. In this experimental study, the effects of EA on CP-induced liver injury were investigated.Material and Methods: Twenty-four Sprague-Dawley rats (180-220 gr) were separated into four equal groups. A single dose of 150 mg/kg CP was given intraperitoneally to generate hepatotoxicity. Different doses (50 and 75 mg/kg) of EA were administered orally 20 minutes before, 4 and 8 hours after CP administration. The histopathological evaluation of kidney tissues and immunohistochemical evaluation for caspase-3 were conducted as well as the serum biochemical analyses.Results: CP treated group exhibited a significant increase in serum hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), compared to the control group. Similarly, the total triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) levels increased significantly. Additionally, the high-density lipoprotein cholesterol (HDL-C) levels decreased, which was not significant, compared to the control group. At both EA doses, VLDL-C, AST, ALT levels decreased significantly while HDL-C level revealed a significant increase. 75 mg/kg EA treatment caused a non-significant elevation in total cholesterol (TC) concentration. Microscopic analysis showed a significant congestion, edema, degeneration and necrosis in the livers of CP administered group. However, edema, degeneration, and necrosis were significantly reduced in animals treated with EA-75. In addition, caspase-3 expression significantly decreased in EA-75 group.Conclusion: These results indicate the protective effects of EA in CP-induced hepatotoxicity in rats.

Ellagic Acid Ameliorates Renal Ischemic-Reperfusion Injury Through NOX4/JAK/STAT Signaling Pathway.

Ellagic acid (EA), a natural polyphenolic compound, has been proved to possess multiple biological activities including alleviating ischemic-reperfusion (I/R) injury. The aim of this current study was to investigate whether EA alleviates I/R injury via regulating inflammatory signaling pathway. Rats were subjected to ischemic-reperfusion (I/R) injury and given orally with different doses of EA before surgery. H&E staining, ELISA assay, and biochemical index analysis were performed to evaluate renal injury and inflammatory factors. Oxidative stress level was detected by DCFH-DA staining and corresponding assay kits. In addition, TUNEL assay and flow cytometric assay were applied for exploring the apoptosis of tissue and cells, respectively. Western blot assay was used to assess protein expressions in tissue and cells. The results showed that EA attenuated the renal I/R injury and reserved renal cell function in vivo. The levels of TNF-a, IL-1β, IL-6, and MCP-1, oxidative stress level, and apoptosis were suppressed in EA-treated rats. Mechanistic studies showed that EA suppressed the phosphorylation of JAK1, JAK2, and STAT1 and reduced the NOX4 level. EA reduced apoptosis, hypoxia-induced inflammatory response, and ROS levels. Moreover, overexpression of NOX4 reversed the protective function with NOX4 inhibition, indicating that the effect of EA against renal IRI or cell hypoxia/reoxygenation might mainly depend on NOX4. The results suggest that EA exerts the renoprotective effect via suppressing NOX4/JAK/STAT signaling pathway, which may be a novel potential therapy for the treatment of acute kidney injury in clinic.

Pharmacodynamic Effect of Ellagic Acid on Ameliorating Cerebral Ischemia/Reperfusion Injury

Cerebral ischemia/reperfusion (I/R) injury causes a larger population of disable patients and deaths annually. Three Tibetan prescriptions have been applied in alleviating the I/R injury for a 1,000 years. Interestingly, ellagic acid (EA) is one of the commonly dominated phytochemicals in these 3 prescriptions. Therefore, it is noteworthy to evaluate the association between the pharmacodynamics effects of EA and I/R injury alleviation. In this study, we reveal that the EA can effectively reduce the infarction area, and prevent the neuron from apoptosis and damage in permanent middle cerebral artery occlusion rat model. The results of the histopathological study indicate that alleviation of brain damage is positively correlated with the EA dose. Further by biochemical analysis, it indicates that the EA can alleviate the brain damage by the anti-inflammatory and anti-oxidative response mediated by EA. The upregulation of zonula occludens-1 and down-regulation of Aquaporin 4 and matrix metalloprotein 9 (MMP-9) in injured brain tissues after being treated with EA suggested that the reconstruction of brain-blood-barrier (BBB), which can further prevent the brain from further injury by the other xenobiotics. In addition, EA will not activate the coagulation factors XII to induce coagulation formation during the treatment process. Therefore, EA is a promising candidate oral drug for I/R injury therapy.

Ellagic acid dose and time-dependently abrogates d-galactose-induced animal model of aging: Investigating the role of PPAR-γ

AimsThe world's population is becoming aged and the proportion of older persons is growing in almost every country in the world. Ellagic acid (EA) shows abundant pharmacological properties. Therefore, we aimed to determine the mechanism of anti-aging effects of low and high doses of EA. Main methodsAging model was induced by d-galactose (DG), and the anti-aging effect of EA alone or in the presence of PPAR-γ antagonist GW9662, and in combination with metformin were evaluated. The activities of ALT, AST, and AChE, the levels of FBS, HbA1c, testosterone and DHEA-SO4, MDA, GSH, TNF-α, IL-6, advanced glycation end products (AGEs), and BDNF were measured in serum, liver or brain. Key findingsDG led to increasing in the levels of IL-6, TNF-α, MDA, AChE, AGEs, ALT, AST, FBS, and HbA1c, in which decrease in the levels of body weight, GSH, BDNF, DHEA-SO4 and testosterone. Metformin (300 mg/kg) abrogated the effects of DG-induced aging model. We also found that the low dose of EA (30 mg/kg) decreases the deteriorative effects of DG-induced aging at 10 weeks of treatment only, however, high dose of EA (100 mg/kg) was effective at both 6 and 10 weeks of treatment. The addition of GW9662 completely reversed the effects of the low dose of EA, but not for the high dose, on DG-induced aging model. SignificanceWe revealed that daily and oral administration of EA provides anti-aging effects at low dose in a PPAR-γ receptor-dependent fashion, but not at the high dose.

Implication of NMDA-NO pathway in the antidepressant-like effect of ellagic acid in male mice

Depression is one the common psychiatric disorders through the world. Nitric oxide (NO) and N-methyl-d-aspartate receptor (NMDA-R) are involved in the pathophysiology of depression. Previous studies have been reported various pharmacological properties for ellagic acid (EA). We aimed to evaluate possible involvement of NMDA-NO pathway in the antidepressant-like effect of EA. To do this, we used relevant behavioral tests to evaluate depressive-like behavior. In order to find effective and sub-effective doses of agents, mice treated with EA (6.25, 12.5, 25, 50 and 100 mg/kg), L-NAME (5 and 10 mg/kg), L-arg (25 and 50 mg/kg), NMDA (75 and 150 mg/kg) and ketamine (0.25 and 0.5 mg/kg). Furthermore, mice were treated with combination of sub-effective dose of EA plus sub-effective doses of L-NAME and/or ketamine as well as treated with effective dose of EA in combination of effective doses of L-arg and/or NMDA. Level of NO and gene expression of NR2A and NR2B subunits of NMDA-R were assessed in the hippocampus. Results showed that EA dose dependently provoked antidepressant-like effects and also decreased the hippocampal NO level as well as expression of NMDA-Rs. Co-administration of sub-effective doses of L-NAME or ketamine with sub-effective dose of EA potentiated the effect of EA on behaviors, NO level as well as NMDA-Rs gene expression in the hippocampus. However, co-treatment of effective dose of EA with effective doses of L-arg or NMDA mitigated effects of EA. In conclusion, our data suggested that NMDA-NO, partially at least, are involved in the antidepressant-like effect of EA.

Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study

Failure of treatment for cancer in clinic by radio/chemotherapy is generally attributed to tumour resistance. Therefore, it is important to develop strategies to increase the cytotoxicity of tumour cells by radiation in combination with unique tumour selective cytotoxic agents. We evaluated the potential of ellagic acid (EA) as an enhancer of oxidative stress in cancer cells. HepG2 cells were treated with EA (10 µM) for 12 h prior to exposure of single 7.5 Gy dose of irradiation. Treatment of HepG2 cells with EA and gamma radiation showed increased reactive oxygen species generation, up regulation of p53 protein expression, decreased survival markers level like p-Akt, p-NF-kB and p-STAT3 which were significantly higher after radiation treatment alone. We also found that combination treatment increased G2/M phase cell population, decreased IL-6, COX–2 and TNF-α expression and caused a loss in mitochondrial membrane potential with decreased level of angiogenesis marker MMP-9. Over expression of Bax and activation of caspase 3 indicated the apoptosis of the cells. The results provided a strong unique strategy to kill cancer cells HepG2, using less radiation dose along with effective pro-oxidant dose of EA.

Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments

Context In a previous study, it has been shown that ellagic acid (EA), a polyphenolic compound found in pomegranate and different berries, prevents cognitive and hippocampal long-term potentiation (LTP) impairments induced by traumatic brain injury in rats through antioxidant and anti-inflammatory mechanisms.Objective The present study was conducted to assess the potential of EA as a memory enhancer.Materials and methods The elevated plus maze (EPM) and passive avoidance (PA) paradigm were used to evaluate learning and memory parameters. Three doses (10, 30 and 100 mg/kg, i.p.) of EA were administered to animals. Memory impairment was induced by scopolamine treatment (0.4 mg/kg, i.p.) and/or diazepam (1 mg/kg, i.p.). Acquisition trials were carried out 30 min after scopolamine treatment and retention trials were performed for 5 min 24 h after the acquisition trials.Results EA at doses 30 and 100 mg/kg significantly reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) in the EPM and PA tests in mice. Also, EA at doses 30 and 100 mg/kg significantly antagonized the amnesia induced by diazepam (1 mg/kg, i.p.) in EPM test in rats. Moreover, chronic administration of EA at dose 30 mg/kg ameliorated the memory deficit induced by diazepam (1 mg/kg, i.p.) in rats.Discussion and conclusion This study demonstrates that ellagic acid is effective in preventing scopolamine- and diazepam-induced cognitive impairments without altering the animals’ locomotion. This suggests the potential of EA application as a useful memory restorative agent in the treatment of dementia seen in elderly persons.

Role of ellagic acid in regulation of apoptosis by modulating novel and atypical PKC in lymphoma bearing mice.

BackgroundProtein kinase C regulates various cellular processes including cell proliferation, cell adhesion, apoptosis, angiogenesis, invasion, and metastasis. Activation of different PKC isozymes results in distinct cellular responses. Novel PKCs are mainly involved in apoptotic process. Atypical PKC subfamily plays a critical role in cell proliferation and apoptosis, cell differentiation and motility. However, Atypical PKCs show contradictory regulation in different tissues or cancer cells. The mechanism of diversified effects is not well explored. Antioxidant ellagic acid shows hepatoprotective, anti-carcinogenic and anti-mutagenic properties. Present study is focused to analyze the effect of ellagic acid on novel and atypical isozymes of PKC in regulation of PKC-mediated apoptosis in liver of lymphoma bearing mice. Implication of ellagic acid treatment to DL mice was analyzed on caspase-3 mediated apoptosis via PKCδ induced activation; and on maintenance of adequate supply of energy during cancer growth.Methods15–20 weeks old adult DL mice were divided into four groups (n = 6). Group 2, 3, 4 were treated with different doses of ellagic acid (40 mg/kg, 60 mg/kg and 80 mg/kg bw). The mice were sacrificed after 19 days of treatment and liver was used for study. The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes. Apoptotic potentiality of ellagic acid was checked on activities of caspase-3 and PKCδ in terms of their catalytic fragments. Aerobic glycolysis was monitored by LDH activity, especially activity of LDH A.ResultsEllagic acid treatment caused up regulation of expression of almost all novel and atypical PKC isozymes. Activities of PKCδ and caspase-3 were enhanced by ellagic acid, however activities of total LDH and LDH-A were inhibited.ConclusionThe results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCδ induced caspase-3 activation; and inhibition of glycolytic pathway.

Erratum to “A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat”

Erratum to “A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat”

Ellagic acid enhances the antinociceptive action of venlafaxine in mouse acetic acid-induced pain: An isobolographic analysis

BackgroundSeveral antidepressants have been used to treat severe pain in clinics. Recently, it has been shown that ellagic acid (EA), a major constituent of pomegranate juice, produced antinociceptive and anti-inflammatory effect through the central and peripheral sites of action. Materials and methodsIn this study, we examined the interaction between EA and venlafaxine (VLF) on pain induced by intraperitoneal acetic acid in mice using isobolographic analysis. ResultsEA (0.3–10mg/kg, ip) and VLF (3–60mg/kg, ip) produced a dose-dependent inhibition of the writhing response evoked by acetic acid. Fifty percent effective dose (ED50) values against writhing behaviors were 1.02 (0.86–1.19)mg/kg and 12.37 (9.74–15.37)mg/kg for EA and VLF, respectively, and also with higher potency than that of VLF. Co-administration of increasing fractional increments of ED50 doses of EA and VLF produced synergistic interaction against writhing behaviors, as revealed by isobolographic analysis. ConclusionThe synergistic action of EA and VLF provides valuable tool referring to the management of visceral pain.