Effects of Epigallocatechin Gallate on Behavioral and Cognitive Impairments, Hypothalamic-Pituitary-Adrenal Axis Dysfunction, and Alternations in Hippocampal BDNF Expression Under Single Prolonged Stress

J Med Food. 2018 Oct;21(10):979-989. doi: 10.1089/jmf.2017.4161. Epub 2018 Sep 29.


Post-traumatic stress disorder (PTSD) is a traumatic stress-related psychiatric disorder stimulated by experience. Green tea has potent antioxidative properties, due, in part, to the catechin (-) epigallocatechin-3-gallate (EGCG). EGCG is an important polyphenol with advantageous effects on anxiety and depression. Nevertheless, the mechanism about the inhibition of PTSD-like symptoms of EGCG is still unidentified. We examined whether EGCG improved learning and memory deficit stimulated in rats after single prolonged stress (SPS). Rats were administrated intraperitoneally (i.p.) with EGCG for 14 successive days after the SPS process. The SPS procedure stimulated cognitive deficit in the Morris water maze test and the object recognition task, and this impairment was improved by EGCG (25 mg/kg, i.p.). Daily EGCG administration significantly decreased the freezing response to contextual fear conditioning. The administration of EGCG also significantly moderated memory-related decreases in the alternation of cAMP-response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Our results suggest that EGCG alleviated SPS-stimulated learning and memory deficit by inhibiting the increase of neuroinflammation in the rat brain. In addition, EGCG reversed the alternation of allopregnanolone and progesterone in the brain, and diminished simultaneously the hypothalamic-pituitary-adrenal axis dysfunction. Thus, EGCG reversed learning and memory-related behavioral dysfunction and molecular alternation accelerated by traumatic stress and may be a useful therapeutic material for PTSD.

Keywords: brain-derived neurotrophic factor; epigallocatechin gallate; hypothalamic–pituitary–adrenal axis; memory; post-traumatic stress disorder; proinflammatory.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Disease Models, Animal
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Humans
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiopathology
  • Rats
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / metabolism
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Physiological


  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Catechin
  • epigallocatechin gallate