Pinocembrin protects rats against cerebral ischemic damage through soluble epoxide hydrolase and epoxyeicosatrienoic acids / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
;
(6): 207-213, 2013.
Article
in English
| WPRIM
| ID: wpr-812703
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Brain
/
Brain Ischemia
/
Arachidonic Acids
/
Rats, Sprague-Dawley
/
Protective Agents
/
Flavanones
/
Disease Models, Animal
/
Drug Therapy
/
Epoxide Hydrolases
/
Genetics
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Chinese Journal of Natural Medicines (English Ed.)
Year:
2013
Type:
Article
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