Neuroprotective effect of apigenin against cerebral ischemia/reperfusion injury

J Int Med Res. 2020 Sep;48(9):300060520945859. doi: 10.1177/0300060520945859.


Objective: The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain. The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury, both in vitro and in vivo.

Methods: We first treated PC12 cells with cobalt chloride (CoCl2) to create a model of oxidative stress injury. Cell viability was then determined using a multifunctional microplate reader. In addition, reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potentials (MMPs) were examined using high-content cytometer analysis. The efficacy of apigenin treatment was also analyzed in a rat middle cerebral artery occlusion (MCAO) model using TTC staining and neurological deficit scores.

Results: The half-inhibitory concentration of CoCl2 was 1.2 mM. Pretreatment with 10 µg ⋅ mL-1 apigenin significantly enhanced cell viability, reduced ROS levels, alleviated apoptosis, and improved MMP in PC12 cells with CoCl2-induced injury in vitro. In addition, apigenin treatment in vivo significantly improved neurological deficit scores and reduced infarct areas in MCAO rats. These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation.

Conclusions: Apigenin had excellent neuroprotective effects for the treatment of cerebral ischemia/reperfusion injury in vitro and in vivo.

Keywords: Cerebral ischemia/reperfusion; PC12 cell model; apigenin; flavonoids; middle cerebral artery occlusion rat model; mitochondria; neuropharmacology; oxidative stress.

MeSH terms

  • Animals
  • Apigenin / pharmacology
  • Apoptosis
  • Brain Ischemia* / drug therapy
  • Infarction, Middle Cerebral Artery / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress
  • Rats
  • Reperfusion Injury* / drug therapy


  • Neuroprotective Agents
  • Apigenin