Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

Oxid Med Cell Longev. 2021 Mar 11:2021:6660193. doi: 10.1155/2021/6660193. eCollection 2021.

Abstract

Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Cerebrovascular Disorders* / metabolism
  • Cerebrovascular Disorders* / pathology
  • Cerebrovascular Disorders* / prevention & control
  • NF-E2-Related Factor 2 / metabolism*
  • Palmitates / pharmacology*
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / pathology
  • Reperfusion Injury* / prevention & control
  • Signal Transduction / drug effects*
  • omega-Chloroacetophenone

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Palmitates
  • omega-Chloroacetophenone
  • AMP-Activated Protein Kinases