Ellagic Acid Inhibits Neuroinflammation and Cognitive Impairment Induced by Lipopolysaccharides

Neurochem Res. 2020 Oct;45(10):2456-2473. doi: 10.1007/s11064-020-03105-z. Epub 2020 Aug 10.

Abstract

Neuroinflammation is a predisposing factor for the development of cognitive impairment and dementia. Among the new molecules that are currently being studied, ellagic acid (EA) has stood out for its neuroprotective properties. The present study investigated the effects of ellagic acid in the object recognition test, oxidative stress, cholinergic neurotransmission, glial cell expression, and phosphorylated Tau protein expression. For this, 32 male Wistar rats received an intraperitoneal (IP) application of lipopolysaccharides (LPS) at a dose of 250 µg/kg or 0.9% saline solution (SAL) for 8 days. Two hours after the IP injections, the animals received 100 mg/kg of EA or SAL via intragastric gavage. Behavioral parameters (open field test and object recognition) were performed on days 5, 6, and 7 of the experimental periods. The results showed that the treatment with EA in the LPS group was able to inhibit cognitive impairment, modulate the immune system response by significantly reducing glial cell expression, attenuating phosphorylated Tau and oxidative damage with consequent improvement in the antioxidant system, as well as preventing the increase of acetylcholinesterase activity. Thus, the neuroprotective effects of EA and its therapeutic potential in cognitive disorders secondary to neuroinflammation were demonstrated.

Keywords: Acetylcholinesterase; Astrocytes; Ellagic acid; Microglia; Oxidative stress; Rats.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Body Weight / drug effects
  • Cerebral Cortex / drug effects
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Ellagic Acid / therapeutic use*
  • Hippocampus / drug effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Lipopolysaccharides
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Open Field Test / drug effects
  • Oxidative Stress / drug effects
  • Phosphorylation / drug effects
  • Rats, Wistar
  • tau Proteins / chemistry
  • tau Proteins / metabolism

Substances

  • Lipopolysaccharides
  • Mapt protein, rat
  • Neuroprotective Agents
  • tau Proteins
  • Ellagic Acid
  • Acetylcholinesterase