1, 8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats. (20th April 2021)

• Record Type: Journal Article
• Authors: Meng, Chen; Zeng, Wenjing; Lv, Jing; Wang, Yu; Gao, Meiling; Chang, Ruijie; Li, Qing; Wang, Xianyu
• Is Part Of: Journal of pharmacy and pharmacology. Volume 73:Number 7(2021)
• Page Start: 979
• Page End: 985
• Publication Date: 2021-04-20
• Subjects: 1 -- 8-cineole -- stroke -- TRPC cation channels -- calpain -- apoptosis -- cyclic AMP response element-binding protein; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1093/jpp/rgab035
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: A previous in vitro study reported that the monoterpene oxide 1, 8-cineole (cineole) attenuates neuronal caused by oxygen–glucose deprivation/reoxygenation in culture. However, to date, there is no in vivo evidence showing neuroprotective effects of cineole against stroke. This study aimed to investigate whether cineole attenuates cerebral ischaemic damage in rats. Methods: A rat model of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion was applied. Male rats were treated with oral cineole (100 mg/kg) for 7 consecutive days, then subjected to MCAO surgery. Infarct volume, neurologic deficits, apoptosis and expression levels of all-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated CREB (p-CREB) were measured in ischaemic brain tissues. Key findings: Cineole treatment significantly reduced infarct volume, neurological dysfunction, neuronal apoptosis, SBDP145 formation and TRPC6 degradation and enhanced p-CREB expression in MCAO rats compared with vehicle treatment. These neuroprotective effects were markedly suppressed by pharmacological inhibition of MEK or CaMKIV signalling. Conclusions: Our study provides in vivo evidence demonstrating that cineole pretreatment attenuates ischaemic stroke-induced brain damage, mainly through blocking calpain-induced TRPC6 degradation and activating CREB via MEK/CREB and CaMKIV/CREB signalling pathways.