Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice.
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors which belong to the nuclear receptor family. We examined whether PPARalpha agonists and resveratrol, a polyphenol contained in grapes, protect the brain against ischemia. To investigate whether resveratrol activates PPARs, we performed a cell-based transfection activity assay using luciferase reporter plasmid. PPARalpha and PPARgamma were activated by resveratrol in primary cortical cultures and vascular endothelial cells. Resveratrol (20 mg/kg, 3 days) reduced infarct volume by 36% at 24 h after middle cerebral artery occlusion in wild-type mice. The PPARalpha agonists fenofibrate (30 mg/kg, 3 days) and Wy-14643 (30 mg/kg, days) exerted similar brain protection. However, resveratrol and fenofibrate failed to protect the brain in PPARalpha knockout mice. The data indicate that PPARalpha agonists protect the brain through PPARalpha.
Inoue
Hiroyasu
H
Department of Pharmacology, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, 565-8565, Osaka, Japan.
Jiang
Xiao Fan
XF
Katayama
Takahiro
T
Osada
Shiho
S
Umesono
Kazuhiko
K
Namura
Shobu
S
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D000882:Haplorhini; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000172:deficiency* / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D020521:Stroke / Q000378:metabolism / Q000517:prevention & control*; D014157:Transcription Factors / Q000819:agonists / Q000172:deficiency* / Q000235:genetics
D018160:Receptors, Cytoplasmic and Nuclear; D013267:Stilbenes; D014157:Transcription Factors; D000077185:Resveratrol; D011345:Fenofibrate