title: β-Caryophyllene Attenuates Focal Cerebral Ischemia-Reperfusion Injury by Nrf2/HO-1 Pathway in Rats.
abstract: This study aimed to identify the effect of β-caryophyllene (BCP) pretreatment and elucidate the Nrf2/HO-1 signaling mechanism after focal cerebral ischemia-reperfusion (I-R) injury in rats. Adult male Sprague-Dawley rats were randomly assigned to the sham-operated group, I-R group and BCP pretreated I-R group. At 24 h after reperfusion, neurological deficits and infarct volume were evaluated. Pathological changes of neuron in hippocampuses were observed by Nissil staining and transmission electron microscopy (TEM). Oxidative stress was assessed by malondialdehyde (MDA) level, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD) and Catalase (CAT) activity. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were analysed by Western blotting and real-time quantitative polymerase chain reaction (Q-PCR). The protein expression of Bcl-2 and Bax was determined by immunohistochemistry. Apoptotic cells were detected using TUNEL staining. In I-R group, neurological deficit scores, cerebral infarct volume, MDA levels, LPO content, NO level, expression of Bax and TUNEL-positive cells were found to be increased at 24 h after I-R injury, while SOD activity, CAT activity and expression of Bcl-2 were decreased. However, results in the BCP pretreatment groups were reversed. And the protein and mRNA expressions of Nrf2 and HO-1 were significantly up-regulated in the BCP pretreated I-R group. Results of Nissil staining and TEM scan manifested that BCP remarkablely improved neuronal injury after I-R in rats. All the above suggested that BCP pretreatment played a neuroprotective role in cerebral I-R injury, which might be exerted by upregulating the expression of Nrf2 and HO-1 to ameliorate oxidative damage and neuronal apoptosis.
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, District of Yuzhong, 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, District of Yuzhong, Chongqing, 400016, China.
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Cao
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, District of Yuzhong, Chongqing, 400016, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, District of Yuzhong, Chongqing, 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, District of Yuzhong, Chongqing, 400016, China. dongzhidyx@163.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, District of Yuzhong, Chongqing, 400016, China. xulu62@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D000081223:Polycyclic Sesquiterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C024714:caryophyllene; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: HO-1; Ischemia-reperfusion injury; Neuroprotection; Nrf2; β-Caryophyllene