Farrerol Alleviates Cerebral Ischemia–Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation

• DOI: 10.1007/s12035-024-04031-9
• Publication Date: 2024-02-20T08:02:26Z
• Authors: Rui Zhao; Xin Zhou; Zhiyuan Zhao; Wenhao Liu; Mengfei Lv; Zhaolong Zhang; Changxin Wang; Tianli Li; Zixiong Yang; Qi Wan; Rui Xu; Yu Cui
• Keywords: Neurons; Male; Cell Survival; NF-kappa B; Apoptosis; Brain Ischemia; Mice, Inbred C57BL; Mice; Glucose; Neuroprotective Agents; Reperfusion Injury; Neuroinflammatory Diseases; Animals; Microglia; Cyclic AMP Response Element-Binding Protein

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.