β-Caryophyllene Pretreatment Alleviates Focal Cerebral Ischemia-Reperfusion Injury by Activating PI3K/Akt Signaling Pathway
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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.
Keywordsβ-Caryophyllene Ischemic-reperfusion injury Neuroprotection Apoptosis PI3K/Akt signaling pathway
Funding was provided by Chongqing Research Program of Basic Research and Frontier Technology (No. cstc2016jcyjA0373).
- 6.Li X, Wu C, Chen N, Gu H, Yen A, Cao L, Wang E, Wang L (2016) PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma. Oncotarget 7:33440–33450Google Scholar
- 7.Terragni J, Graham JR, Adams KW, Schaffer ME, Tullai JW, Cooper GM (2008) Phosphatidylinositol 3-kinase signaling in proliferating cells maintains an anti-apoptotic transcriptional program mediated by inhibition of FOXO and non-canonical activation of NFkappaB transcription factors. BMC Cell Biol 9:6CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Zhang L, Ravipati AS, Koyyalamudi SR, Jeong SC, Reddy N, Bartlett J, Smith PT, de la Cruz M, Monteiro MC, Melguizo Á, Jiménez E, Vicente F (2013) Anti-fungal and anti-bacterial activities of ethanol extracts of selected traditional Chinese medicinal herbs. Asian Pacific. J Trop Med 6:673–681Google Scholar
- 19.Ljubisavljevic MR, Javid A, Oommen J, Parekh K, Nagelkerke N, Shehab S, Adrian TE (2015) The effects of different repetitive transcranial magnetic stimulation (rTMS) protocols on cortical gene expression in a rat model of cerebral ischemic-reperfusion Injury. PLoS One 10:e0139892Google Scholar
- 20.Walker TL, Kempermann G (2014) One mouse, two cultures: isolation and culture of adult neural stem cells from the two neurogenic zones of individual mice. J Vis Exp 84:e51225Google Scholar
- 50.Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT (2008) An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 68:6084–6091CrossRefPubMedPubMedCentralGoogle Scholar