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Pinocembrin protects rats against cerebral ischemic damage through soluble epoxide hydrolase and epoxyeicosatrienoic acids
- Source :
- Chinese Journal of Natural Medicines. 11:207-213
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- To investigate the relationship between cerebroprotection of pinocembrin and epoxyeicosatrienoic acids (EETs) and their regulating enzyme soluble epoxide hydrolase (sEH).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.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.Inhibiting sEH and then increasing the potency of EETs may be one of the mechanisms through which pinocembrin provides cerebral protection.
- Subjects :
- Epoxide Hydrolases
Male
chemistry.chemical_classification
Epoxide hydrolase 2
Pinocembrin
Chemistry
Brain
Ischemic injury
Arachidonic Acids
General Medicine
Protective Agents
Brain Ischemia
Rats
Rats, Sprague-Dawley
Disease Models, Animal
chemistry.chemical_compound
Enzyme
Complementary and alternative medicine
Biochemistry
Flavanones
Drug Discovery
cardiovascular system
Animals
Humans
lipids (amino acids, peptides, and proteins)
Subjects
Details
- ISSN :
- 18755364
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Chinese Journal of Natural Medicines
- Accession number :
- edsair.doi.dedup.....684e94f5bb1eea20a9b42979cb56fce2