• Jian-Feng Liang, Xiao-Dan Qin, Xue-Hong Huang, Zi-Ping Fan, Yong-Ying Zhi, Jia-Wei Xu, Fangmei Chen, Zhi-Li Pan, Yi-Fei Chen, Chang-Bo Zheng, and Jun Lu.
• Guangxi Key Laboratory of Drug Discovery and Optimization, School of Pharmacy, Guilin Medical University, Guilin 541199, China; Lushan Rehabilitation and Recuperation Center, Jiujiang 332000, China.
• Neuroscience. 2024 Aug 30; 554: 9610696-106.

AbstractCerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18β-GA) in ameliorates CIRI. Our results showed that 18β-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18β-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18β-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18β-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18β-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18β-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18β-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.

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