Alkaloid rich fraction from Nelumbo nucifera targets VSMC proliferation and migration to suppress restenosis in balloon-injured rat carotid artery

Jun, MY; Karki, R; Paudel, KR; Sharma, BR; Adhikari, D; Kim, DW

Alkaloid rich fraction from Nelumbo nucifera targets VSMC proliferation and migration to suppress restenosis in balloon-injured rat carotid artery

Jun, MY Karki, R Paudel, KR

Sharma, BR Adhikari, D Kim, DW

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Publication Type:: Journal Article
Citation:: Atherosclerosis, 2016, 248 pp. 179 - 189
Issue Date:: 2016-05-01

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Field	Value	Language
dc.contributor.author	Jun, MY	en_US
dc.contributor.author	Karki, R	en_US
dc.contributor.author	Paudel, KR https://orcid.org/0000-0002-3591-2080	en_US
dc.contributor.author	Sharma, BR	en_US
dc.contributor.author	Adhikari, D	en_US
dc.contributor.author	Kim, DW	en_US
dc.date.accessioned	2020-03-25T23:32:49Z
dc.date.available	2016-03-16	en_US
dc.date.available	2020-03-25T23:32:49Z
dc.date.issued	2016-05-01	en_US
dc.identifier.citation	Atherosclerosis, 2016, 248 pp. 179 - 189	en_US
dc.identifier.issn	0021-9150	en_US
dc.identifier.uri	http://hdl.handle.net/10453/139537
dc.description.abstract	© 2016 Elsevier Ireland Ltd. Aims: Restenosis- an adverse consequence following angioplasty, and atherosclerosis are characterized by abnormal vascular smooth muscle cell (VSMC) proliferation and migration leading to neo-intima formation. In the present study, we investigated the inhibitory effects of alkaloid rich fraction (ARF) from Nelumbo nucifera and isolated compound neferine on platelet-derived growth factor (PDGF-BB) induced VSMC proliferation and migration in vitro and neo-intima formation in a rat carotid artery injury model. Methods: PDGF-BB induced VSMC proliferation and migration was assessed using colorimetric assay and modified Boyden chamber method respectively. Gene expression of cell cycle associated molecules was determined by reverse transcription-polymerase chain reaction (RT-PCR). The signaling molecules such as PDGF-Rβ, extracellular regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), P38, metalloproteinase (MMP)-9 and nuclear factor-kappa B (NF-κB) were determined by western blot analysis. Stress fiber formation was evaluated using immunofluorescence microscopy. The rat carotid artery balloon injury model was performed to assess the effect of ARF on neo-intima formation. Results: ARF possessed the strongest anti-oxidant activities. The anti-proliferative activity of both ARF and neferine was due to suppression of cyclin D1, cyclin E and cyclin-dependent kinase (Cdk) gene expression. Moreover, ARF and neferine inhibited PDGF-Rβ, ERK1/2, JNK and P38 activations and NF-κB translocation. Also, ARF and neferine inhibited VSMC migration by inhibiting MMP-9 activity without affecting cytoskeleton remodeling. In a rat carotid artery injury model, ARF inhibited neo-intima formation. Conclusion: Our results indicate that ARF targets VSMC proliferation and migration to attenuate neo-intima formation by inhibition of PDGF-Rβ mediated signaling.	en_US
dc.relation.ispartof	Atherosclerosis	en_US
dc.relation.isbasedon	10.1016/j.atherosclerosis.2016.03.020	en_US
dc.subject.classification	Cardiovascular System & Hematology	en_US
dc.subject.mesh	Muscle, Smooth, Vascular	en_US
dc.subject.mesh	Carotid Arteries	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Rats, Sprague-Dawley	en_US
dc.subject.mesh	Nelumbo	en_US
dc.subject.mesh	Carotid Artery Injuries	en_US
dc.subject.mesh	Carotid Stenosis	en_US
dc.subject.mesh	Biphenyl Compounds	en_US
dc.subject.mesh	Picrates	en_US
dc.subject.mesh	Alkaloids	en_US
dc.subject.mesh	Receptor, Platelet-Derived Growth Factor beta	en_US
dc.subject.mesh	Proto-Oncogene Proteins c-sis	en_US
dc.subject.mesh	NF-kappa B	en_US
dc.subject.mesh	Plant Extracts	en_US
dc.subject.mesh	Chelating Agents	en_US
dc.subject.mesh	Free Radical Scavengers	en_US
dc.subject.mesh	Antioxidants	en_US
dc.subject.mesh	Angioplasty, Balloon	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	MAP Kinase Signaling System	en_US
dc.subject.mesh	Lipid Peroxidation	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Neointima	en_US
dc.subject.mesh	Becaplermin	en_US
dc.title	Alkaloid rich fraction from Nelumbo nucifera targets VSMC proliferation and migration to suppress restenosis in balloon-injured rat carotid artery	en_US
dc.type	Journal Article
utslib.citation.volume	248	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	248	en_US

Abstract:

© 2016 Elsevier Ireland Ltd. Aims: Restenosis- an adverse consequence following angioplasty, and atherosclerosis are characterized by abnormal vascular smooth muscle cell (VSMC) proliferation and migration leading to neo-intima formation. In the present study, we investigated the inhibitory effects of alkaloid rich fraction (ARF) from Nelumbo nucifera and isolated compound neferine on platelet-derived growth factor (PDGF-BB) induced VSMC proliferation and migration in vitro and neo-intima formation in a rat carotid artery injury model. Methods: PDGF-BB induced VSMC proliferation and migration was assessed using colorimetric assay and modified Boyden chamber method respectively. Gene expression of cell cycle associated molecules was determined by reverse transcription-polymerase chain reaction (RT-PCR). The signaling molecules such as PDGF-Rβ, extracellular regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), P38, metalloproteinase (MMP)-9 and nuclear factor-kappa B (NF-κB) were determined by western blot analysis. Stress fiber formation was evaluated using immunofluorescence microscopy. The rat carotid artery balloon injury model was performed to assess the effect of ARF on neo-intima formation. Results: ARF possessed the strongest anti-oxidant activities. The anti-proliferative activity of both ARF and neferine was due to suppression of cyclin D1, cyclin E and cyclin-dependent kinase (Cdk) gene expression. Moreover, ARF and neferine inhibited PDGF-Rβ, ERK1/2, JNK and P38 activations and NF-κB translocation. Also, ARF and neferine inhibited VSMC migration by inhibiting MMP-9 activity without affecting cytoskeleton remodeling. In a rat carotid artery injury model, ARF inhibited neo-intima formation. Conclusion: Our results indicate that ARF targets VSMC proliferation and migration to attenuate neo-intima formation by inhibition of PDGF-Rβ mediated signaling.

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http://hdl.handle.net/10453/139537