Myricetin suppresses traumatic brain injury-induced inflammatory response via EGFR/AKT/STAT pathway

Sci Rep. 2023 Dec 20;13(1):22764. doi: 10.1038/s41598-023-50144-x.

Abstract

Traumatic brain injury (TBI) is a common disease in neurosurgery with a high fatality and disability rate which imposes a huge burden on society and patient's family. Inhibition of neuroinflammation caused by microglia activation is a reasonable strategy to promote neurological recovery after TBI. Myricetin is a natural flavonoid that has shown good therapeutic effects in a variety of neurological disease models, but its therapeutic effect on TBI is not clear. We demonstrated that intraperitoneal injection of appropriate doses of myricetin significantly improved recovery of neurological function after TBI in Sprague Dawley rats and inhibited excessive inflammatory responses around the lesion site. Myricetin dramatically reduced the expression of toxic microglia markers generated by TBI and LPS, according to the outcomes of in vivo and in vitro tests. In particular, the expression of inducible nitric oxide synthase, cyclooxygenase 2, and some pro-inflammatory cytokines was reduced, which protected learning and memory functions in TBI rats. Through network pharmacological analysis, we found that myricetin may inhibit microglia hyperactivation through the EGFR-AKT/STAT pathway. These findings imply that myricetin is a promising treatment option for the management of neuroinflammation following TBI.

MeSH terms

  • Animals
  • Brain Injuries, Traumatic* / pathology
  • Disease Models, Animal
  • ErbB Receptors / metabolism
  • Flavonoids / metabolism
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Humans
  • Microglia / metabolism
  • Neuroinflammatory Diseases
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • myricetin
  • Proto-Oncogene Proteins c-akt
  • Flavonoids
  • ErbB Receptors
  • EGFR protein, human