title: Protection of salvianolic acid A on rat brain from ischemic damage via soluble epoxide hydrolase inhibition.
abstract: Epoxyeicosatrienoic acids (EETs) and their regulating enzyme soluble epoxide hydrolase (sEH) have been associated with ischemic stroke. Salvianolic acid A (SAA) is proved to display potent cerebroprotection. However, little information is available about the link between them. This study aimed to investigate whether SAA exhibits its protective effects in rats subjected to middle cerebral artery occlusion (MCAO) through sEH and EETs. The results showed that SAA treatment ameliorated neurological deficits and reduced infarct volume. Notably, the beneficial effects of SAA were attenuated by co-administration of (14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE)), a putative selective EETs antagonist. Furthermore, SAA increased the 14,15-EET levels in the blood and brain of sham and MCAO rats. Assay for hydrolase activity showed that 1 and 3 mg/kg of SAA significantly diminished brain sEH activity of MCAO rats. A fluorescent assay in vitro indicated that SAA could inhibit recombinant human sEH activity in a concentration-dependent manner (IC(50) = 1.62 μmol/l). Immunohistochemical analysis showed that SAA at the doses of 1 and 3 mg/kg significantly decreased sEH protein expression in hippocampus CA1 region of MCAO rats. In conclusion, cerebral protection of SAA is mediated, at least in part, via inhibiting sEH to increase EETs levels.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China.
authors.forename: Shou-Bao
authors.initials: SB
authors.lastname: Wang
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Pang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Yang
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Fang
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000032:analysis / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002109:Caffeic Acids; D007773:Lactates; C066201:salvianolic acid A; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid