title: β-Caryophyllene Pretreatment Alleviates Focal Cerebral Ischemia-Reperfusion Injury by Activating PI3K/Akt Signaling Pathway.
abstract: β-Caryophyllene (BCP) has been reported to be protective against focal cerebral ischemia-reperfusion (I/R) injury by its anti-oxidative and anti-inflammatory features. Recent study demonstrates that the BCP exhibits potential neuroprotection against I/R injury induced apoptosis, however, the mechanism remains unknown. Therefore, we investigate the underlying anti-apoptotic mechanism of BCP pretreatment in I/R injury. Sprague-Dawley rats (pretreated with BCP suspensions or solvent orally for 7 days) were subjected to transient Middle Cerebral Artery Occlusion (MCAO) for 90 min, followed by 24 h reperfusion. Results showed that BCP pretreatment improved the neurologic deficit score, lowered the infarct volume and decreased number of apoptotic cells in the hippocampus. Moreover, in western blot and RT-qPCR detections, BCP pretreatment down-regulated the expressions of Bax and p53, up-regulated the expression of Bcl-2, and enhanced the phosphorylation of Akt on Ser473. Blockage of PI3K activity by wortmannin not only abolished the BCP-induced decreases in infarct volume and neurologic deficit score, but also dramatically abrogated the enhancement of AKt phosphorylation. Our results suggested that BCP pre-treatment protects against I/R injury partly by suppressing apoptosis via PI3K/AKt signaling pathway activation.
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China.
authors.forename: Ruidi
authors.initials: R
authors.lastname: An
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Tian
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China.
authors.forename: Minghang
authors.initials: M
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lou
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China. xulu62@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, 400016, China. dongzhidyx@163.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C024714:caryophyllene
keywords: Apoptosis; Ischemic-reperfusion injury; Neuroprotection; PI3K/Akt signaling pathway; β-Caryophyllene