Protection of salvianolic acid A on rat brain from ischemic damage via soluble epoxide hydrolase inhibition |
| |
| Authors: | Shou-Bao Wang Xiao-Bin Pang Yan Zhao Yue-Hua Wang Li Zhang Xiu-Ying Yang |
| |
| Affiliation: | 1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Beijing , 100050 , China;2. Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , 100050 , China;3. Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , 100050 , China;4. Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , 100050 , China;5. Qingdao Municipal Hospital , Qingdao , 266011 , China |
| |
| 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 (IC50 = 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. |
| |
| Keywords: | salvianolic acid A cerebral ischemic damage soluble epoxide hydrolase epoxyeicosatrienoic acids |
|
|
