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2014 ; 92
(4
): 590-8
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Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell
proliferation and neointimal formation
#MMPMID25316569
Huo Y
; Yi B
; Chen M
; Wang N
; Chen P
; Guo C
; Sun J
Biochem Pharmacol
2014[Dec]; 92
(4
): 590-8
PMID25316569
show ga
Nur77 is an orphan nuclear receptor that belongs to the nuclear receptor 4A
(NR4A) subfamily, which has been implicated in a variety of biological events,
such as cell apoptosis, proliferation, inflammation, and metabolism. Activation
of Nur77 has recently been shown to be beneficial for the treatment of
cardiovascular and metabolic diseases. The purpose of this study is to identify
novel natural Nur77 activators and investigate their roles in preventing vascular
diseases. By measuring Nur77 expression using quantitative RT-PCR, we screened
active ingredients extracted from Chinese herb medicines with beneficial
cardiovascular effects. Hyperoside (quercetin 3-D-galactoside) was identified as
one of the potent activators for inducing Nur77 expression and activating its
transcriptional activity in vascular smooth muscle cells (VSMCs). We demonstrated
that hyperoside, in a time and dose dependent manner, markedly increased the
expression of Nur77 in rat VSMCs, with an EC50 of ?0.83 ?M. Mechanistically, we
found that hyperoside significantly increased the phosphorylation of ERK1/2 MAP
kinase and its downstream target cAMP response element-binding protein (CREB),
both of which contributed to the hyperoside-induced Nur77 expression in rat
VSMCs. Moreover, through activation of Nur77 receptor, hyperoside markedly
inhibited both vascular smooth muscle cell proliferation in vitro and the carotid
artery ligation-induced neointimal formation in vivo. These findings demonstrate
that hyperoside is a potent natural activator of Nur77 receptor, which can be
potentially used for prevention and treatment of occlusive vascular diseases.