Ginkgetin Promotes M2 Polarization of Microglia and Exert Neuroprotection in Ischemic Stroke via Modulation of PPARγ Pathway

Neurochem Res. 2022 Oct;47(10):2963-2974. doi: 10.1007/s11064-022-03583-3. Epub 2022 May 20.

Abstract

Neuroinflammation plays an important role in the pathophysiological process of acute cerebral infarction, which may aggravate brain injury and hinder neuro-repair. Microglia are innate immune cells in the brain. Ginkgetin has anti-inflammatory and neuroprotective effects, but the mechanism remains unclear. This study aims to explore the regulatory effects of ginkgetin on microglia polarization in brain ischemia. Oxygen glucose deprivation (OGD) cellular model and middle cerebral artery occlusion (MCAO) animal model was used in this study. We first observed the dynamic process of microglia polarization in ischemic stroke, and then investigated the effect of ginkgetin treatment on microglia polarization. Finally, we studied the role of PPARγ signaling pathway and the blocking effect of PPARγ antagonist GW9662 in this process. OGD and cerebral ischemia polarized microglia mainly to M1 type. However, ginkgetin treatment converted microglia from M1 type to M2 type, inhibited neuroinflammation, and exerted neuronal protective effects. PPARγ signaling pathway was activated during this process. The above effects could be blocked by GW9662. Ginkgetin can promote M2 polarization of microglia through PPARγ signaling pathway, thereby inhibiting neuroinflammation and promoting recovery of neurological functions in ischemic stroke.

Keywords: Ginkgetin; Ischemic stroke; Microglia; Neuroinflammation; Polarization.

MeSH terms

  • Anilides
  • Animals
  • Biflavonoids
  • Brain Ischemia* / metabolism
  • Infarction, Middle Cerebral Artery / metabolism
  • Ischemic Stroke*
  • Microglia / metabolism
  • Neuroprotection
  • PPAR gamma / metabolism
  • Stroke* / drug therapy
  • Stroke* / metabolism

Substances

  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Biflavonoids
  • PPAR gamma
  • ginkgetin