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Pseudoginsenoside-F11 promotes functional recovery after transient cerebral ischemia by regulating the microglia/macrophage polarization in rats.

Abstract
The polarization of microglia/macrophages after cerebral ischemia is critical for post-stroke damage/recovery. Previously, we found that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has neuroprotective effects on permanent and transient cerebral ischemia in rats. This study aimed to investigate the effects and potential mechanisms of PF11 on microglia/macrophage polarization following transient cerebral ischemia in rats. In vivo data showed that oral administration of PF11 (12 mg/kg) significantly attenuated cognitive deficits and sensorimotor dysfunction, infarct volume and brain edema in transient middle cerebral artery occlusion (tMCAO)-treated rats, as well as reduced the loss of neurons and the over-activation of microglia in penumbra of ipsilateral striatum and cortex. Notably, the proportion of M2 microglia/macrophages in the total activated microglia/macrophages peaked on day 14 after tMCAO in rats, while PF11 promoted its peak advancing to day 3 post-tMCAO, which allowing the damaged brain to enter the repair period more quickly. Furthermore, PF11 increased the expression of anti-inflammatory markers and decreased the expression of pro-inflammatory markers in ipsilateral striatum and cortex. In addition, in vitro data showed that PF11 inhibited the induction of M1 microglia by oxygen glucose deprivation/re-oxygenation (OGD/R)-induced neurons, and promoted the polarization of microglia to M2 phenotype in a Jumonji domain-containing protein 3 (Jmjd3)-dependent manner. Moreover, PF11 promoted the protection of M2 microglia and attenuated the exacerbation of M1 microglia on OGD/R-induced neuronal damage. Taken together, these results indicate that PF11 protects ischemic neurons by promoting M2 microglia/macrophage polarization in a Jmjd3-dependent manner, ultimately facilitating the functional recovery following transient cerebral ischemia.
AuthorsYing Hou, Depeng Yang, Xianshi Wang, Huiyang Wang, Haotian Zhang, Pengwei Wang, Yinglu Liu, Xiaoyun Gao, Jingyu Yang, Chunfu Wu
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 99 Pg. 107896 (Oct 2021) ISSN: 1878-1705 [Electronic] Netherlands
PMID34246061 (Publication Type: Journal Article)
CopyrightCopyright © 2021. Published by Elsevier B.V.
Chemical References
  • Cytokines
  • Ginsenosides
  • Neuroprotective Agents
  • pseudoginsenoside F11
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm6b protein, rat
  • Glucose
Topics
  • Animals
  • Brain (drug effects, immunology)
  • Cell Hypoxia (drug effects)
  • Cells, Cultured
  • Cytokines (genetics)
  • Ginsenosides (pharmacology, therapeutic use)
  • Glucose (deficiency)
  • Infarction, Middle Cerebral Artery (drug therapy, genetics, immunology)
  • Ischemic Attack, Transient (drug therapy, genetics, immunology)
  • Jumonji Domain-Containing Histone Demethylases (genetics)
  • Macrophages (cytology, drug effects)
  • Male
  • Microglia (cytology, drug effects)
  • Neurons (drug effects)
  • Neuroprotective Agents (pharmacology, therapeutic use)
  • Rats, Sprague-Dawley
  • Rats

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