%0 Journal Article
%T Farrerol Alleviates Cerebral Ischemia-Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation.
%A Zhao R
%A Zhou X
%A Zhao Z
%A Liu W
%A Lv M
%A Zhang Z
%A Wang C
%A Li T
%A Yang Z
%A Wan Q
%A Xu R
%A Cui Y
%J Mol Neurobiol
%V 0
%N 0
%D 2024 Feb 20
%M 38376762
%F 5.682
%R 10.1007/s12035-024-04031-9
%X Ischemia-reperfusion (I/R) injury is a key influencing factor in the outcome of stroke. Inflammatory response, oxidative stress, and neuronal apoptosis are among the main factors that affect the progression of I/R injury. Farrerol (FAR) is a natural compound that can effectively inhibit the inflammatory response and oxidative stress. However, the role of FAR in cerebral I/R injury remains unknown. In this study, we found that FAR reduced brain injury and neuronal viability after cerebral I/R injury. Meanwhile, administration of FAR also reduced the inflammatory response of microglia after brain injury. Mechanistically, FAR treatment directly reduced neuronal death after oxygen glucose deprivation/re-oxygenation (OGD/R) through enhancing cAMP-response element binding protein (CREB) activation to increase the expression of downstream neurotrophic factors and anti-apoptotic genes. Moreover, FAR decreased the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, inhibited microglia activation, and reduced the production of inflammatory cytokines in microglia after OGD/R treatment or LPS stimulation. The compromised inflammatory response by FAR directly promoted the survival of neurons after OGD/R. In conclusion, FAR exerted a protective effect on cerebral I/R injury by directly decreasing neuronal death through upregulating CREB expression and attenuating neuroinflammation. Therefore, FAR could be a potentially effective drug for the treatment of cerebral I/R injury.