Pinocembrin protects rats against cerebral ischemic damage through soluble epoxide hydrolase and epoxyeicosatrienoic acids.
10.1016/S1875-5364(13)60018-7
- Author:
Shou-Bao WANG
1
;
Xiao-Bin PANG
;
Mei GAO
;
Lian-Hua FANG
;
Guan-Hua DU
Author Information
1. Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Arachidonic Acids;
metabolism;
Brain;
drug effects;
enzymology;
metabolism;
Brain Ischemia;
drug therapy;
enzymology;
genetics;
metabolism;
prevention & control;
Disease Models, Animal;
Epoxide Hydrolases;
genetics;
metabolism;
Flavanones;
administration & dosage;
Humans;
Male;
Protective Agents;
administration & dosage;
Rats;
Rats, Sprague-Dawley
- From:
Chinese Journal of Natural Medicines (English Ed.)
2013;11(3):207-213
- CountryChina
- Language:English
-
Abstract:
AIM:To investigate the relationship between cerebroprotection of pinocembrin and epoxyeicosatrienoic acids (EETs) and their regulating enzyme soluble epoxide hydrolase (sEH).
METHODS:Rats underwent middle cerebral artery occlusion (MCAO) to mimic permanent focal ischemia, and pinocembrin was administrated via tail vein injection at 10 min, 4 h, 8 h and 23 h after MCAO. After 24 MCAO, rats were re-anesthetized, and the blood and brain were harvested and analyzed.
RESULTS:Pinocembrin displayed significant protective effects on MCAO rats indicated by reduced neurological deficits and infarct volume. Importantly, co-administration of 0.2 mg·kg(-1) 14, 15-EEZE, a putative selective EET antagonist, weakened the beneficial effects of pinocembrin. 14, 15-EET levels in the blood and brain of rats after 24 h MCAO were elevated in the presence of pinocembrin. In an assay for hydrolase activity, pinocembrin significantly lowered brain sEH activity of MCAO rats and inhibited recombinant human sEH activity in a concentration-dependent manner (IC50, 2.58 μmol·L(-1)). In addition, Western blot and immunohistochemistry analysis showed that pinocembrin at doses of 10 mg·kg(-1) and 30 mg·kg(-1) significantly down-regulated sEH protein in rat brain, especially the hippocampus CA1 region of MCAO rats.
CONCLUSION:Inhibiting sEH and then increasing the potency of EETs may be one of the mechanisms through which pinocembrin provides cerebral protection.
