The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic, linoleic, and other fatty acid epoxides, endogenous chemical mediators that play an important role in blood pressure regulation and inflammation. AUDA is a potent sEH inhibitor with IC50s of 18±1 and 69±2 nM for the mouse and human sEH, respectively[1]. AUDA (0.3 to 10 μg/mL) dose-dependently suppressed the proliferation of rat VSMCs (vascular smooth muscle cells) exposed to PDGF (platelet-derived growth factor) for 48 h. AUDA (1–30 μg/mL) dose-dependently inhibited the protein expression of Pin1 and increased HO-1 (heme oxygenase-1) protein levels in PDGF-treated VSMCs at a dose of 3 μg/mL, although potent induction was seen only at 30 μg/mL. PDGF increased COX-2 protein levels in rat VSMCs, and AUDA (1–30 μg/mL; 30 min) dose-dependently upregulated COX-2 expression[2]. Furthermore, in the mouse model of Kawasaki disease (KD), AUDA reduced the protein expression of MMP-9, IL-1β and TNF-α, indicating that AUDA may alleviate inflammatory reactions in the coronary arteries of KD model mice[3].
AUDA 细胞实验
Cell Line
Concentration
Treated Time
Description
References
prefrontal cortex neurons
1 μM, 5 μM, 10 μM
10 min
To evaluate the effect of AUDA on excitatory synaptic transmission in prefrontal cortex neurons. Results showed that AUDA significantly increased the amplitude of EPSCs and fEPSPs, indicating enhanced excitatory synaptic transmission.
J Biomed Sci. 2015 Oct 22;22:94
3T3-L1 preadipocytes
1 µM
12 h
To evaluate the effect of EETs combined with AUDA on PPARγ target gene expression. Results showed that EETs combined with AUDA increased the mRNA level of adipocyte P2.
Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16747-52
Human umbilical vein endothelial cells (HUVECs)
1 µM
12 h
To evaluate the effect of EETs combined with AUDA on PPARγ target gene expression. Results showed that EETs combined with AUDA increased the mRNA level of fatty acid-binding protein 4.
Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16747-52
Bovine aortic endothelial cells (BAECs)
1 µM
8 h
To evaluate the effect of EETs combined with AUDA on PPARγ transcriptional activity. Results showed that EETs significantly increased PPARγ transcriptional activity in the presence of AUDA.
Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16747-52
Rat VSMCs
0.3 to 30 µg/mL
24 h
To evaluate the effect of AUDA on HO-1 and Keap1 expression. AUDA dose-dependently reduced Keap1 levels and increased HO-1 protein levels.
Int J Mol Sci. 2017 Dec 11;18(12):2683
Rat VSMCs
0.3 to 10 µg/mL
48 h
To evaluate the effect of AUDA on PDGF-induced proliferation of rat VSMCs. AUDA significantly inhibited PDGF-induced rat VSMC proliferation.
Int J Mol Sci. 2017 Dec 11;18(12):2683
AUDA 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Male Sprague-Dawley rats
Angiotensin-dependent hypertensive model
Oral
25 mg/L
14 days
Lower blood pressure and ameliorate renal damage
Hypertension. 2005 Oct;46(4):975-81
Goto-Kakizaki rats
Hypertension and type II diabetes model
Drinking water
25 mg/L
14 days
AUDA treatment reduced renal damage in hypertensive Goto-Kakizaki rats, decreased urinary albumin excretion and monocyte/macrophage infiltration, and inhibited MCP-1 gene expression and urinary excretion.
Clin Sci (Lond). 2009 Jan;116(1):61-70
Rats
Spontaneously hypertensive stroke-prone (SHRSP) rats and normotensive Wistar-Kyoto (WKY) rats
Drinking water
2 mg/day
Daily administration for 6 weeks
To investigate the protective effects of AUDA against cerebral ischemia in normotension and hypertension. Results showed that AUDA reduced hemispheric infarct size and neurodeficit score in SHRSP rats via vascular and neural protection, while in WKY rats, it primarily provided neural protection.
Am J Pathol. 2009 Jun;174(6):2086-95
C57Bl/6 mice
Middle cerebral artery occlusion (MCAO) model
Intraperitoneal injection
10 mg/kg
Single injection, lasting 24 hours
To evaluate the protective effect of AUDA-BE on ischemic brain injury, results showed that AUDA-BE significantly reduced infarct size
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