Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain Injury via Inhibition of Inflammatory Mediators and Down-regulation of JNK/p38 MAPK Activation

Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 (D10). On D10, the rats were subjected to HI brain injury. Following HI injury, infarct size, weight and volume of the brain were measured. Apoptosis was assessed by Fluoro-Jade C staining. Expression of caspases (caspase-3, 8 and 9), apoptotic pathway proteins (Bax, Bad, Bcl-2 and Bcl-xL), MAPKs, NF κB(p65) and p-IK-Bα were assessed by western blotting. mRNA levels of inflammatory mediators (TNF-α, IL-1α, IL-1β, iNOS, COX-2) were analyzed. Results: Ellagic acidmarkedly (p < 0.05) reduced infarct size, volume and tissue loss. Significant (p < 0.05) reduction in neuroapoptosis was observed on pre treatment with ellagic acid. Expression levels of caspases, apoptotic pathway proteins and MAPK proteins were down-regulated with marked (p < 0.05) suppression of inflammatory mediators, NF-κB(p65) and p-IK-Bα. Conclusion: Ellagic acid affords neuroprotection in HI brain injury by inhibiting apoptosis, inflammatory responses and modulating the proteins of apoptotic and MAPK pathways. Thus, ellagic acid may be a potent candidate for the treatment of HI injury. Keywords: Brain injury, Ellagic acid, Hypoxia, Inflammatory mediators, Mitogen activated protein kinases, Neuroprotective

• Publication year

  2016

• Venue

  Tropical Journal of Pharmaceutical Research

• Publication date

  2016-03-04

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.4314/TJPR.V15I2.4
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Neuroprotective effects of bilobalide on cerebral ischemia and reperfusion injury are associated with inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation

  2014cited by this paper
• Ellagic acid inhibits VEGF/VEGFR2, PI3K/Akt and MAPK signaling cascades in the hamster cheek pouch carcinogenesis model.

  2014cited by this paper
• Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

  2013cited by this paper
• Anti-Inflammatory Effects of Ellagic Acid on Acute Lung Injury Induced by Acid in Mice

  2013cited by this paper
• The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

  2013cited by this paper
• N-3 Fatty Acid Rich Triglyceride Emulsions Are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice

  2013cited by this paper
• Neuroprotective and Anti-Inflammatory Effects of the Flavonoid-Enriched Fraction AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury

  2012cited by this paper
• Intracellular Signaling MAPK Pathway After Cerebral Ischemia–Reperfusion Injury

  2012cited by this paper
• Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats

  2012cited by this paper
• Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.

  2012cited by this paper
• Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes.

  2012cited by this paper
• Expression of N‐methyl D‐aspartate receptor subunits in amoeboid microglia mediates production of nitric oxide via NF‐κB signaling pathway and oligodendrocyte cell death in hypoxic postnatal rats

  2011cited by this paper
• Mechanisms underlying inflammation in neurodegeneration.

  2010cited by this paper
• Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms.

  2010cited by this paper
• Lipopolysaccharide Sensitizes Neonatal Hypoxic-Ischemic Brain Injury in a MyD88-Dependent Manner1

  2009cited by this paper
• A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy.

  2008cited by this paper
• p38 MAP-kinases pathway regulation, function and role in human diseases.

  2007cited by this paper
• Preconditioning Suppresses Inflammation in Neonatal Hypoxic Ischemia Via Akt Activation

  2007cited by this paper
• Effects of fetal exposure to isoflurane on postnatal memory and learning in rats.

  2007cited by this paper
• Apoptosis-inducing factor is a major contributor to neuronal loss induced by neonatal cerebral hypoxia-ischemia

  2007cited by this paper
• Free radicals, mitochondria, and hypoxia-ischemia in the developing brain.

  2006cited by this paper
• Perinatal brain injury and regulation of transcription

  2006cited by this paper
• Neonatal brain injury.

  2004cited by this paper
• Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid--extensive binding to protein and DNA.

  2003cited by this paper
• NF-kappaB regulation in the immune system.

  2002cited by this paper
• Role of Mitogen- and Stress-Activated Kinases in Ischemic Injury

  2002cited by this paper
• Interleukin-18 Involvement in Hypoxic–Ischemic Brain Injury

  2002cited by this paper
• Synergistic Activation of Caspase-3 by m-Calpain after Neonatal Hypoxia-Ischemia

  2001cited by this paper
• BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia.

  2000cited by this paper
• Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury.

  1998cited by this paper
• A quantitative review of mortality and developmental disability in extremely premature newborns.

  1998cited by this paper
• Guide for the Care and Use of Laboratory Animals

  1996cited by this paper

• Clinical and Mechanistic Exploration of Ellagic Acid in Neurodegenerative Diseases: Targeted Neuroprotection Through Cellular and Molecular Mechanisms

  2025cites this paper
• Ellagic acid improves the symptoms of early-onset Alzheimer's disease: Behavioral and physiological correlates

  2024cites this paper
• Nutraceuticals: A Complementary Approach in the Management of Alzheimer’s Disease

  2023cites this paper
• Phenolic Acids and Prevention of Cognitive Decline: Polyphenols with a Neuroprotective Role in Cognitive Disorders and Alzheimer’s Disease

  2022influential citation
• Potential implications of polyphenolic compounds in neurodegenerative diseases

  2022cites this paper
• Protective activities of ellagic acid and urolithins against kidney toxicity of environmental pollutants: A review.

  2022cites this paper
• The Role of the NMDA Receptor in the Anticonvulsant Effect of Ellagic Acid in Pentylenetetrazole-Induced Seizures in Male Mice

  2022cites this paper
• Understanding Abnormal c-JNK/p38MAPK Signaling Overactivation Involved in the Progression of Multiple Sclerosis: Possible Therapeutic Targets and Impact on Neurodegenerative Diseases

  2021cites this paper
• Ellagic Acid ameliorates Streptozotocin-Induced Diabetic Hyperalgesia in Rat: Involvement of Oxidative Stress

  2021cites this paper
• The Anti-nociceptive Effect of Ellagic Acid in Streptozotocin-induced Hyperglycemic Rats by Oxidative Stress Involvement

  2021cites this paper
• Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

  2020cites this paper
• Pomegranate as a natural source of phenolic antioxidants

  2020cites this paper
• Neuroprotective effects of urolithin A on H2O2-induced oxidative stress-mediated apoptosis in SK-N-MC cells

  2019cites this paper
• Determination of Ellagic Acid Compound Activity as Anti Breast Cancer

  2019cites this paper
• Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis

  2017cites this paper
• The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action

  2017cites this paper
• Ellagic acid in strawberry (Fragaria spp.): Biological, technological, stability, and human health aspects

  2017cites this paper
• Ellagic acid protects against neuron damage in ischemic stroke through regulating the ratio of Bcl-2/Bax expression.

  2017cites this paper
• Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines.

  2016cites this paper