Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroi...

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Published in:Molecular medicine (Cambridge, Mass.) Vol. 30; no. 1; pp. 59 - 18
Main Authors: Kang, Chunyang, Sang, Qiuling, Liu, Dingxi, Wang, Libo, Li, Jia, Liu, Xiaoyang
Format: Journal Article
Language:English
Published: London BioMed Central 14.05.2024
Springer Nature B.V
BMC
Subjects:
Animals
Apoptosis
Autophagy
Autophagy - drug effects
Biomedical and Life Sciences
Biomedicine
Brain
Brain Ischemia - drug therapy
Brain Ischemia - metabolism
Cancer
Carotid arteries
Cell Polarity - drug effects
Cerebral ischemia
Cytokines
Diosgenin - analogs & derivatives
Diosgenin - pharmacology
Diosgenin - therapeutic use
Disease Models, Animal
Infarction, Middle Cerebral Artery - drug therapy
Inflammation
Ischemia
Male
Mice
Mice, Inbred C57BL
Microglia - drug effects
Microglia - metabolism
Microglial polarization
Molecular Medicine
Neuroinflammatory Diseases - drug therapy
Neuroinflammatory Diseases - etiology
Neuroinflammatory Diseases - metabolism
NLRP3 inflammasome
Polyphyllin I (PPI)
Reperfusion Injury - drug therapy
Reperfusion Injury - etiology
Reperfusion Injury - metabolism
Research Article
Signal Transduction - drug effects
Stroke
Surgery
Tissues
TOR Serine-Threonine Kinases - metabolism
Veins & arteries
United States > US
China
Japan
Cerebral ischemia
NLRP3 inflammasome
Microglial polarization
Polyphyllin I (PPI)
Autophagy
ISSN:1528-3658, 1076-1551, 1528-3658
Online Access:Get full text
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Summary:Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia–reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen–glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia–reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia–reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.
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ISSN:1528-3658
1076-1551
1528-3658
DOI:10.1186/s10020-024-00828-5