Potential of Edaravone Dexborneol in the treatment of cerebral ischemia: focus on cell death-related signaling pathways

Mol Biol Rep. 2024 Sep 23;51(1):1007. doi: 10.1007/s11033-024-09952-1.

Abstract

Cerebral ischemia has the highest global rate of morbidity and mortality. It occurs when a sudden occlusion develops in the arterial system, and consequently some parts of the brain are deprived from glucose and oxygen due to the cessation of blood flow. The ensuing reperfusion of the ischemic area results in a cascade of pathological alternations like neuronal apoptosis by producing excessive reactive oxygen species (ROS), oxidative stress and neuroinflammation. Edaravone Dexborneol is a novel agent, comprised of Edaravone and Dexborneol in a 4:1 ratio. It has documented neuroprotective effects against cerebral ischemia injury. Edaravone Dexborneol improves neurobehavioral and sensorimotor function, cognitive function, brain edema, and blood-brain barrier (BBB) integrity in experimental models. It at dosages ranging between 0.375 and 15 mg/kg (from immediately after ischemia until the 28th post-ischemic days) has shown neuroprotective effects in experimental models of cerebral ischemia by inhibiting cell death-signaling pathways. For example, it inhibits apoptosis by increasing Bcl2, and reducing Bax and caspase-3 expression. Edaravone Dexborneol also inhibits pyroptosis by attenuating NF-κB/NLRP3/GSDMD signaling, as well as ferroptosis by activating the Nrf-2/HO-1/GPX4 signaling pathway. It also inhibits autophagy by targeting PI3K/Akt/mTOR signaling pathway. Here, we provide a review on the impacts of Edaravone Dexborneol on cerebral ischemia.

Keywords: Antioxidants; Brain ischemia; Cell death; Edaravone Dexborneol.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Cell Death / drug effects
  • Edaravone* / pharmacology
  • Edaravone* / therapeutic use
  • Humans
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects

Substances

  • Edaravone
  • Neuroprotective Agents
  • Reactive Oxygen Species