Inhibitory Effect of <i>n</i>‐Butylidenephthalide on Neointimal Hyperplasia in Balloon Injured Rat Carotid Artery

Liu, Wei-Shin; Lin, Po Ting; Chang, Li-Fu; Harn, Horng‐Jyh; Shiuan, David; Chiou, Tzyy‐Wen; Jeng, Jing-Ren

doi:10.1002/ptr.3377

Cited by 22 publications

(12 citation statements)

References 22 publications

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“…In vascular SMCs, expression of Nur77 is significantly induced by pathological stimuli, such as PDGF-BB, FBS, ox-LDL, and inflammatory cytokines[47]. Moreover, ectopic expression or pharmacological activation of Nur77 has been shown to inhibit VSMC proliferation in vitro and neointimal formation in vivo[22, 48, 49], suggesting potential therapeutic values of Nur77 activators for the treatment of occlusive vascular diseases, such as atherosclerosis and restenosis [20, 28, 33]. Therefore, identification of potent Nur77 agonist with lower toxicity is of great scientific and therapeutic interests.…”

Section: Discussionmentioning

confidence: 99%

Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation

Huo

Chen

et al. 2014

Biochemical Pharmacology

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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 ∼0.83μM. 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.

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Section: Discussionmentioning

confidence: 99%

Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation

Huo

Chen

et al. 2014

Biochemical Pharmacology

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“…For example, the volatile compounds such as ligustilide, butylidene phthalide and butyl phthalide are said to have antitumor (Kan et al, 2008;Harn et al, 2011;Liu et al, 2011), neuroprotective (Huang et al, 2008;Chen et al, 2011), immunomodulatory (Su et al, 2011) and cardiovascular protective (Yeh et al, 2011) effects. The ferulic acid, the most abundant phenolic non-volatile compound of AS, has been reported for its anti-inflammatory and antioxidant potency (Ozaki, 1992;Ronchetti et al, 2006;Su et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic and myeloprotective activities of an acidic Angelica sinensis polysaccharide on human CD34+ stem cells

Lee

Hsieh

Chen

et al. 2012

Journal of Ethnopharmacology

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“…N-butylidenephthalide (BP), a natural compound isolated from Angelica sinensis , has been investigated for a variety of pharmacological activities, such as antitumor growth, suppression of platelet aggregation, relaxation of vessels and inhibition of VSMCs proliferation [ 4 , 5 ]. In our previous study, we have proved that BP inhibited neointimal hyperplasia in a balloon-injured rat carotid artery due to its dual effects of anti-proliferative and apoptotic induction on VSMCs [ 6 ]. However, little is known about whether BP inhibits the PDGF-induced phenotypic switch of VSMCs as well as inhibiting the formation of stenosis in an arteriovenous fistula.…”

Section: Introductionmentioning

confidence: 99%

N-Butylidenephthalide Inhibits the Phenotypic Switch of VSMCs through Activation of AMPK and Prevents Stenosis in an Arteriovenous Fistula Rat Model

Yang

Chen

et al. 2020

IJMS

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The phenotypic switch of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of vascular disorders, such as atherosclerosis, stenosis and restenosis, after vascular intervention. In our previous study, n-butylidenephthalide (BP) was reported to have anti-proliferating and apoptotic effects on VSMCs. The purpose of the current study is to further investigate its role in platelet-derived growth factor (PDGF)-induced VSMC phenotypic modulation in an arteriovenous fistula model. In vitro, we observed that BP inhibited the PDGF-induced cytoskeleton reorganization of the VSMCs. The enhanced expression of vimentin and collagen, as well as the migration ability induced by PDGF, were also inhibited by BP. By cell cycle analysis, we found that BP inhibited the PDGF-induced VSMCs proliferation and arrested the VSMCs in the G0/G1 phase. In an arteriovenous fistula rat model, the formation of stenosis, which was coupled with a thrombus, and the expression of vimentin and collagen in VSMCs, were also inhibited by administration of BP, indicating that BP inhibited the PDGF-induced phenotypic switch and the migration of VSMCs. Besides, the inhibitory effects of BP on the phenotypic switch were found to accompany the activated 5’ AMP-activated protein kinase (AMPK) as well as the inhibited phosphorylation of mTOR. Knockdown of AMPK by gene silencing conflicted the effects of BP and further exacerbated the PDGF-induced VSMCs phenotypic switch, confirming the modulating effect that BP exerted on the VSMCs by this pathway. These findings suggest that BP may contribute to the vasculoprotective potential in vasculature.

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Inhibitory Effect of n‐Butylidenephthalide on Neointimal Hyperplasia in Balloon Injured Rat Carotid Artery

Cited by 22 publications

References 22 publications

Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation

Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation

Hematopoietic and myeloprotective activities of an acidic Angelica sinensis polysaccharide on human CD34+ stem cells

N-Butylidenephthalide Inhibits the Phenotypic Switch of VSMCs through Activation of AMPK and Prevents Stenosis in an Arteriovenous Fistula Rat Model

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