Cepharanthine inhibits in vitro VSMC proliferation and migration and vascular inflammatory responses mediated by RAW264.7

Paudel, KR; Karki, R; Kim, DW

Cepharanthine inhibits in vitro VSMC proliferation and migration and vascular inflammatory responses mediated by RAW264.7

Paudel, KR

Karki, R Kim, DW

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Publication Type:: Journal Article
Citation:: Toxicology in Vitro, 2016, 34 pp. 16 - 25
Issue Date:: 2016-08-01

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Field	Value	Language
dc.contributor.author	Paudel, KR https://orcid.org/0000-0002-3591-2080	en_US
dc.contributor.author	Karki, R	en_US
dc.contributor.author	Kim, DW	en_US
dc.date.accessioned	2020-03-25T23:32:26Z
dc.date.available	2016-03-20	en_US
dc.date.available	2020-03-25T23:32:26Z
dc.date.issued	2016-08-01	en_US
dc.identifier.citation	Toxicology in Vitro, 2016, 34 pp. 16 - 25	en_US
dc.identifier.issn	0887-2333	en_US
dc.identifier.uri	http://hdl.handle.net/10453/139536
dc.description.abstract	© 2015 Elsevier B.V. Pathogenesis of atherosclerosis involves vascular smooth muscle cell (VSMC) migration and proliferation followed by an inflammation mediated by activated macrophages in the tunica intima of blood vessels. Cepharanthine (CEP) belongs to bisbenzylisoquinoline alkaloids found in the plant Stephania cepharantha, which has been used for various diseases like cancer, alopecia areata, venomous snakebites, and malaria. In this study, we investigated whether CEP suppresses VSMC migration and proliferation and inhibits inflammatory mediator production in macrophage (RAW264.7). Our results showed that CEP possessed significant DPPH scavenging and metal chelating activities. It also markedly inhibited lipid peroxidation. Similarly, CEP suppressed the nitric oxide (NO) production and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in RAW264.7 cells. Moreover, the level of prostaglandin E2 was also suppressed and the formation of macrophage derived foam cell was attenuated in RAW264.7 cells. Likewise, NO production in isolated peritoneal macrophage and VSMC migration in response to LPS stimulated RAW264.7 was also halted by CEP treatment. Also, VSMC migration induced by platelet-derived growth factor (PDGF-BB) was inhibited by CEP dose dependently. The anti-migratory effect of CEP on VSMCs was due to its inhibitory effect on metalloproteinase-9 (MMP-9) expression, preventing the degradation of extracellular matrix (ECM) component. Furthermore, CEP suppressed PDGF-BB induced VSMC proliferation by down-regulation of mitogen activated protein kinase (MAPK) signaling molecules. CEP also inhibited the translocation of NF-κB from cytosol to nucleus. Thus, our results suggest that CEP exerts potent anti-atherosclerotic effect through attenuation of inflammation, lipid peroxidation and VSMC migration and proliferation.	en_US
dc.relation.ispartof	Toxicology in Vitro	en_US
dc.relation.isbasedon	10.1016/j.tiv.2016.03.010	en_US
dc.subject.classification	Toxicology	en_US
dc.subject.mesh	Muscle, Smooth, Vascular	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Iron	en_US
dc.subject.mesh	Nitric Oxide	en_US
dc.subject.mesh	Biphenyl Compounds	en_US
dc.subject.mesh	Picrates	en_US
dc.subject.mesh	Benzylisoquinolines	en_US
dc.subject.mesh	Dinoprostone	en_US
dc.subject.mesh	Proto-Oncogene Proteins c-sis	en_US
dc.subject.mesh	Anti-Inflammatory Agents	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	Lipid Peroxidation	en_US
dc.subject.mesh	Atherosclerosis	en_US
dc.subject.mesh	Cyclooxygenase 2	en_US
dc.subject.mesh	Nitric Oxide Synthase Type II	en_US
dc.subject.mesh	RAW 264.7 Cells	en_US
dc.subject.mesh	Becaplermin	en_US
dc.title	Cepharanthine inhibits in vitro VSMC proliferation and migration and vascular inflammatory responses mediated by RAW264.7	en_US
dc.type	Journal Article
utslib.citation.volume	34	en_US
utslib.for	1115 Pharmacology and Pharmaceutical 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	34	en_US

Abstract:

© 2015 Elsevier B.V. Pathogenesis of atherosclerosis involves vascular smooth muscle cell (VSMC) migration and proliferation followed by an inflammation mediated by activated macrophages in the tunica intima of blood vessels. Cepharanthine (CEP) belongs to bisbenzylisoquinoline alkaloids found in the plant Stephania cepharantha, which has been used for various diseases like cancer, alopecia areata, venomous snakebites, and malaria. In this study, we investigated whether CEP suppresses VSMC migration and proliferation and inhibits inflammatory mediator production in macrophage (RAW264.7). Our results showed that CEP possessed significant DPPH scavenging and metal chelating activities. It also markedly inhibited lipid peroxidation. Similarly, CEP suppressed the nitric oxide (NO) production and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in RAW264.7 cells. Moreover, the level of prostaglandin E2 was also suppressed and the formation of macrophage derived foam cell was attenuated in RAW264.7 cells. Likewise, NO production in isolated peritoneal macrophage and VSMC migration in response to LPS stimulated RAW264.7 was also halted by CEP treatment. Also, VSMC migration induced by platelet-derived growth factor (PDGF-BB) was inhibited by CEP dose dependently. The anti-migratory effect of CEP on VSMCs was due to its inhibitory effect on metalloproteinase-9 (MMP-9) expression, preventing the degradation of extracellular matrix (ECM) component. Furthermore, CEP suppressed PDGF-BB induced VSMC proliferation by down-regulation of mitogen activated protein kinase (MAPK) signaling molecules. CEP also inhibited the translocation of NF-κB from cytosol to nucleus. Thus, our results suggest that CEP exerts potent anti-atherosclerotic effect through attenuation of inflammation, lipid peroxidation and VSMC migration and proliferation.

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http://hdl.handle.net/10453/139536