Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage.
Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage.
Jiang
Jun
J
Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 210029, China.
Wang
Wei
W
Sun
Yong Jun
YJ
Hu
Mei
M
Li
Fei
F
Zhu
Dong Ya
DY
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D027343:Rhizome; D014409:Tumor Necrosis Factor-alpha
D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D030421:Peroxynitrous Acid; D052247:Nitric Oxide Synthase Type II; D003474:Curcumin