Targeting the AKT-P53/CREB pathway with epicatechin for improved prognosis of traumatic brain injury

CNS Neurosci Ther. 2024 Feb;30(2):e14364. doi: 10.1111/cns.14364. Epub 2023 Jul 18.

Abstract

Aims: The aim of this study was to evaluate the effect of epicatechin, on neurological recovery and neuroinflammation after traumatic brain injury (TBI) to investigate its potential value in clinical practice.

Methods: TBI model was established in adult rats by CCI method. The effect of epicatechin was evaluated after intraperitoneal injection. Neurological recovery after TBI was assessed by Morris Water Maze, mNSS score, Rotarod test and Adhesive removal test. Protein and gene expression was assessed by Western blot, ELISA, PCR and immunofluorescence. Furthermore, the use of AKT pathway inhibitors blocked the therapeutic effects of epicatechin clarifying AKT-P53/CREB as a potential pathway for the effects of epicatechin.

Results: Administering epicatechin after TBI prevented neuronal death, reduced neuroinflammation, and promoted neurological function restoration in TBI rats. Network pharmacology study suggested that epicatechin may exert its therapeutic benefits through the AKT-P53/CREB pathway CONCLUSION: These results indicate that epicatechin, a monomeric compound derived from tea polyphenols, possesses potent antioxidant and anti-inflammatory properties after TBI. The mechanism may be related to the regulation of the AKT-P53/CREB signal pathway.

Keywords: epicatechin; inflammation; microglia; neurological function; traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic* / drug therapy
  • Brain Injuries, Traumatic* / metabolism
  • Catechin* / pharmacology
  • Catechin* / therapeutic use
  • Disease Models, Animal
  • Neuroinflammatory Diseases
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Catechin
  • Proto-Oncogene Proteins c-akt
  • Tumor Suppressor Protein p53