Erianin alleviates cerebral ischemia-reperfusion injury by inhibiting microglial cell polarization and inflammation via the PI3K/AKT and NF-κB pathways.
Int Immunopharmacol
; 141: 112915, 2024 Nov 15.
Article
in En
| MEDLINE
| ID: mdl-39146784
ABSTRACT
Cerebral ischemia-reperfusion injury (CI/RI) is a leading cause of disability and mortality worldwide, with limited therapeutic options available. Erianin, a natural compound derived from traditional Chinese medicine, has been reported to possess anti-inflammatory and neuroprotective properties. This study aimed to investigate the therapeutic potential of Erianin in CI/RI and elucidate its underlying mechanisms. Network pharmacology analysis predicted that Erianin could target the PI3K/AKT pathway, which are closely associated with CI/RI. In vivo experiments using a rat model of CI/RI demonstrated that Erianin treatment significantly alleviated neurological deficits, reduced infarct volume, and attenuated neuronal damage. Mechanistically, Erianin inhibited microglial cell polarization towards the pro-inflammatory M1 phenotype, as evidenced by the modulation of specific markers. Furthermore, Erianin suppressed the expression of pro-inflammatory cytokines and mediators, such as TNF-α, IL-6, and COX-2, while enhancing the production of anti-inflammatory factors, including Arg1, CD206, IL-4 and IL-10. In vitro studies using oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated microglial cells corroborated the anti-inflammatory and anti-apoptotic effects of Erianin. Notably, Erianin inhibited the NF-κB signaling pathway by inhibiting p65 phosphorylation and preventing the nuclear translocation of the p65 subunit. Collectively, these findings suggest that Erianin represents a promising therapeutic candidate for CI/RI by targeting microglial cell polarization and inflammation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
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Signal Transduction
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NF-kappa B
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Rats, Sprague-Dawley
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Microglia
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Anti-Inflammatory Agents
Limits:
Animals
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
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FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: