Improvement of cerebral ischemia/reperfusion injury by daucosterol palmitate-induced neuronal apoptosis inhibition via PI3K/Akt/mTOR signaling pathway

Metab Brain Dis. 2020 Aug;35(6):1035-1044. doi: 10.1007/s11011-020-00575-6. Epub 2020 May 4.

Abstract

Traditional Chinese medicine has growing importance in the treatment of ischemia stroke due to its abundance and low drug resistance. In this study, we aim to investigate the therapeutic potential of daucosterol palmitate against ischemia stroke, as well as its neuro-protective mechanism. The dose-response effects of daucosterol palmitate in the protection from brain damage were evaluated in a cerebral ischemia/reperfusion (I/R) rat model. The correlation of neuro-protective effects of daucosterol palmitate with apoptosis inhibition was examined and the possible signaling targets were identified. Our findings revealed that daucosterol palmitate treatment after 2 h' ischemia significantly lowered brain damage, and neuronal cell apoptosis caused by I/R injury in a dose-response mode (20, 40 and 80 mg/kg). Western blot analysis indicated that daucosterol palmitate could reverse the effects of I/R injury on protein expression of PI3K and mTOR, and phosphorylation of Akt. Contrarily, inactivation of PI3K using wortmannin dramatically antagonized the effect of daucosterol palmitate for I/R injury. With these findings, it supports the application potential of daucosterol palmitate in the treatment of ischemia stroke. Besides, the PI3K/Akt/mTOR pathway might be potential cellular targets for daucosterol palmitate.

Keywords: Anti-apoptosis; Cerebral ischemia/reperfusion; Daucosterol palmitate; Neuro-protection; PI3K/Akt/mTOR.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Dose-Response Relationship, Drug
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Palmitates / pharmacology
  • Palmitates / therapeutic use*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Sitosterols / pharmacology
  • Sitosterols / therapeutic use*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Palmitates
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts
  • Sitosterols
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • lyoniside