title: Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling.
abstract: The effects of curcumin (CCM) on cerebral ischemia/reperfusion injury are not well understood. The aim of this study was to investigate whether CCM attenuates inflammation and mitochondrial dysfunction in a rat model of cerebral ischemia/reperfusion injury and whether Sirt1 is involved in these potential protective effects. Sirtinol, a Sirt1 inhibitor, was used to elucidate the underlying mechanism. Rats were subjected to 2h of transient middle cerebral artery occlusion (MCAO), followed by reperfusion for 24h. Brain magnetic resonance imaging (MRI) was used to detect infarct volumes. Neurological scores and brain water content were also assessed. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in the brain were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Expression of SIRT1, acetylated p53 (Ac-p53), Bcl-2, and Bax was measured by western blotting. Our results suggested that CCM exerted a neuroprotective effect, as shown by reduced infarct volumes and brain edema and improved neurological scores. CCM also exerted anti-inflammatory effects, as indicated by decreased TNF-α and IL-6 levels in the brain. CCM elevated mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial cytochrome c levels, but reduced cytosolic cytochrome c levels. Moreover, CCM upregulated SIRT1 and Bcl-2 expression and downregulated Ac-p53 and Bax expression. These effects of CCM were abolished by sirtinol. In conclusion, our results demonstrate that CCM treatment attenuates ischemic stroke-induced brain injury via activation of SIRT1.
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, China.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: ltyradiology@sina.com.
authors.forename: Tianyou
authors.initials: T
authors.lastname: Luo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D003474:Curcumin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015395:Histocompatibility Antigens Class I; D017382:Reactive Oxygen Species; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D003474:Curcumin
keywords: Cerebral ischemia; Curcumin; Mitochondrial dysfunction; Sirt1 signaling