The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05

In a previous study, HMC05, a water extract from eight medicinal herbs was demonstrated to possess anti-inflammatory effects in murine macrophages and anti-atherosclerotic effects in apoE −/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteri...

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Veröffentlicht in:Journal of ethnopharmacology 2011-01, Vol.133 (1), p.168-176
Hauptverfasser: Lee, Jo Woon Yi, Lee, Bok-Soo, Lee, Ji Yeun, Ku, Hyo Jung, Jeon, So-Ra, Kim, Joo Yun, Ban, Ji Min, Sung, Sang Hyun, Shin, Heung Mook, Park, Jeong Euy
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container_title Journal of ethnopharmacology
container_volume 133
creator Lee, Jo Woon Yi
Lee, Bok-Soo
Lee, Ji Yeun
Ku, Hyo Jung
Jeon, So-Ra
Kim, Joo Yun
Ban, Ji Min
Sung, Sang Hyun
Shin, Heung Mook
Park, Jeong Euy
description In a previous study, HMC05, a water extract from eight medicinal herbs was demonstrated to possess anti-inflammatory effects in murine macrophages and anti-atherosclerotic effects in apoE −/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using in vivo balloon injury rat model and in vitro biochemical assays. A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis. There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25 mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats. HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.
doi_str_mv 10.1016/j.jep.2010.09.015
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HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using in vivo balloon injury rat model and in vitro biochemical assays. A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&amp;E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis. There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25 mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats. HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2010.09.015</identifier><identifier>PMID: 20883768</identifier><identifier>CODEN: JOETD7</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>animal models ; animal tissues ; Animals ; Anti-Inflammatory Agents - pharmacology ; arterial intima ; atherosclerosis ; Balloon injury model ; biochemical pathways ; Biological and medical sciences ; blood flow ; carotid arteries ; Carotid Arteries - drug effects ; Carotid Arteries - metabolism ; Carotid Artery Injuries - pathology ; Catheterization ; cell migration ; Cell Movement - drug effects ; cell proliferation ; Cell Proliferation - drug effects ; Cells, Cultured ; Coronary Restenosis - prevention &amp; control ; Disease Models, Animal ; dosage ; dose response ; drug formulations ; General pharmacology ; Herb ; herbal medicines ; histopathology ; HMC05 ; HSP27 Heat-Shock Proteins - metabolism ; Humans ; hyperplasia ; immunohistochemistry ; in vitro studies ; in vivo studies ; inflammation ; Male ; mechanism of action ; Medical sciences ; medicinal plants ; Mice ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - pathology ; Neointima - prevention &amp; control ; neointima formation ; Neointimal hyperplasia ; oral administration ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Phytotherapy ; plant extracts ; Plant Extracts - pharmacology ; Plants, Medicinal ; Plaque, Atherosclerotic - pathology ; Plaque, Atherosclerotic - prevention &amp; control ; Platelet-Derived Growth Factor - metabolism ; Proto-Oncogene Proteins c-sis ; Rats ; Restenosis ; Signal Transduction ; smooth muscle ; stenosis</subject><ispartof>Journal of ethnopharmacology, 2011-01, Vol.133 (1), p.168-176</ispartof><rights>2010 Elsevier Ireland Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ireland Ltd. 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HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using in vivo balloon injury rat model and in vitro biochemical assays. A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&amp;E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis. There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25 mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats. HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.</description><subject>animal models</subject><subject>animal tissues</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>arterial intima</subject><subject>atherosclerosis</subject><subject>Balloon injury model</subject><subject>biochemical pathways</subject><subject>Biological and medical sciences</subject><subject>blood flow</subject><subject>carotid arteries</subject><subject>Carotid Arteries - drug effects</subject><subject>Carotid Arteries - metabolism</subject><subject>Carotid Artery Injuries - pathology</subject><subject>Catheterization</subject><subject>cell migration</subject><subject>Cell Movement - drug effects</subject><subject>cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Coronary Restenosis - prevention &amp; control</subject><subject>Disease Models, Animal</subject><subject>dosage</subject><subject>dose response</subject><subject>drug formulations</subject><subject>General pharmacology</subject><subject>Herb</subject><subject>herbal medicines</subject><subject>histopathology</subject><subject>HMC05</subject><subject>HSP27 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>hyperplasia</subject><subject>immunohistochemistry</subject><subject>in vitro studies</subject><subject>in vivo studies</subject><subject>inflammation</subject><subject>Male</subject><subject>mechanism of action</subject><subject>Medical sciences</subject><subject>medicinal plants</subject><subject>Mice</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Neointima - prevention &amp; control</subject><subject>neointima formation</subject><subject>Neointimal hyperplasia</subject><subject>oral administration</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. 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HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using in vivo balloon injury rat model and in vitro biochemical assays. A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&amp;E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis. There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25 mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats. HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>20883768</pmid><doi>10.1016/j.jep.2010.09.015</doi><tpages>9</tpages></addata></record>
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identifier ISSN: 0378-8741
ispartof Journal of ethnopharmacology, 2011-01, Vol.133 (1), p.168-176
issn 0378-8741
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subjects animal models
animal tissues
Animals
Anti-Inflammatory Agents - pharmacology
arterial intima
atherosclerosis
Balloon injury model
biochemical pathways
Biological and medical sciences
blood flow
carotid arteries
Carotid Arteries - drug effects
Carotid Arteries - metabolism
Carotid Artery Injuries - pathology
Catheterization
cell migration
Cell Movement - drug effects
cell proliferation
Cell Proliferation - drug effects
Cells, Cultured
Coronary Restenosis - prevention & control
Disease Models, Animal
dosage
dose response
drug formulations
General pharmacology
Herb
herbal medicines
histopathology
HMC05
HSP27 Heat-Shock Proteins - metabolism
Humans
hyperplasia
immunohistochemistry
in vitro studies
in vivo studies
inflammation
Male
mechanism of action
Medical sciences
medicinal plants
Mice
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - pathology
Neointima - prevention & control
neointima formation
Neointimal hyperplasia
oral administration
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Phytotherapy
plant extracts
Plant Extracts - pharmacology
Plants, Medicinal
Plaque, Atherosclerotic - pathology
Plaque, Atherosclerotic - prevention & control
Platelet-Derived Growth Factor - metabolism
Proto-Oncogene Proteins c-sis
Rats
Restenosis
Signal Transduction
smooth muscle
stenosis
title The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05
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