Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet

Oral administration of rhamnan sulfate (RS), derived from the seaweed <i>Monostroma nitidum</i>, markedly suppresses inflammatory damage in the vascular endothelium and organs of lipopolysaccharide-treated mice. This study aimed to analyze whether orally administered RS inhibits the deve...

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Main Authors: Masahiro Terasawa, Liqing Zang, Keiichi Hiramoto, Yasuhito Shimada, Mari Mitsunaka, Ryota Uchida, Kaoru Nishiura, Koichi Matsuda, Norihiro Nishimura, Koji Suzuki
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/12/22/2666
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author Masahiro Terasawa
Liqing Zang
Keiichi Hiramoto
Yasuhito Shimada
Mari Mitsunaka
Ryota Uchida
Kaoru Nishiura
Koichi Matsuda
Norihiro Nishimura
Koji Suzuki
author_facet Masahiro Terasawa
Liqing Zang
Keiichi Hiramoto
Yasuhito Shimada
Mari Mitsunaka
Ryota Uchida
Kaoru Nishiura
Koichi Matsuda
Norihiro Nishimura
Koji Suzuki
author_sort Masahiro Terasawa
collection DOAJ
description Oral administration of rhamnan sulfate (RS), derived from the seaweed <i>Monostroma nitidum</i>, markedly suppresses inflammatory damage in the vascular endothelium and organs of lipopolysaccharide-treated mice. This study aimed to analyze whether orally administered RS inhibits the development of atherosclerosis, a chronic inflammation of the arteries. ApoE-deficient female mice were fed a normal or high-fat diet (HFD) with or without RS for 12 weeks. Immunohistochemical and mRNA analyses of atherosclerosis-related genes were performed. The effect of RS on the migration of RAW264.7 cells was also examined in vitro. RS administration suppressed the increase in blood total cholesterol and triglyceride levels. In the aorta of HFD-fed mice, RS reduced vascular smooth muscle cell proliferation, macrophage accumulation, and elevation of VCAM-1 and inhibited the reduction of Robo4. Increased mRNA levels of <i>Vcam1</i>, <i>Mmp9</i>, and <i>Srebp1</i> in atherosclerotic areas of HFD-fed mice were also suppressed with RS. Moreover, RS directly inhibited the migration of RAW264.7 cells in vitro. Thus, in HFD-fed ApoE-deficient mice, oral administration of RS ameliorated abnormal lipid metabolism and reduced vascular endothelial inflammation and hyperpermeability, macrophage infiltration and accumulation, and smooth muscle cell proliferation in the arteries leading to atherosclerosis. These results suggest that RS is an effective functional food for the prevention of atherosclerosis.
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spelling doaj.art-ed8017d96a8e416ea02ace770495909e2023-11-24T14:35:33ZengMDPI AGCells2073-44092023-11-011222266610.3390/cells12222666Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat DietMasahiro Terasawa0Liqing Zang1Keiichi Hiramoto2Yasuhito Shimada3Mari Mitsunaka4Ryota Uchida5Kaoru Nishiura6Koichi Matsuda7Norihiro Nishimura8Koji Suzuki9Konan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, JapanGraduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, JapanFaculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho, Suzuka 513-8670, JapanDepartment of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu 514-8507, JapanDepartment of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu 514-8507, JapanKonan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, JapanKonan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, JapanKonan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, JapanGraduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, JapanFaculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho, Suzuka 513-8670, JapanOral administration of rhamnan sulfate (RS), derived from the seaweed <i>Monostroma nitidum</i>, markedly suppresses inflammatory damage in the vascular endothelium and organs of lipopolysaccharide-treated mice. This study aimed to analyze whether orally administered RS inhibits the development of atherosclerosis, a chronic inflammation of the arteries. ApoE-deficient female mice were fed a normal or high-fat diet (HFD) with or without RS for 12 weeks. Immunohistochemical and mRNA analyses of atherosclerosis-related genes were performed. The effect of RS on the migration of RAW264.7 cells was also examined in vitro. RS administration suppressed the increase in blood total cholesterol and triglyceride levels. In the aorta of HFD-fed mice, RS reduced vascular smooth muscle cell proliferation, macrophage accumulation, and elevation of VCAM-1 and inhibited the reduction of Robo4. Increased mRNA levels of <i>Vcam1</i>, <i>Mmp9</i>, and <i>Srebp1</i> in atherosclerotic areas of HFD-fed mice were also suppressed with RS. Moreover, RS directly inhibited the migration of RAW264.7 cells in vitro. Thus, in HFD-fed ApoE-deficient mice, oral administration of RS ameliorated abnormal lipid metabolism and reduced vascular endothelial inflammation and hyperpermeability, macrophage infiltration and accumulation, and smooth muscle cell proliferation in the arteries leading to atherosclerosis. These results suggest that RS is an effective functional food for the prevention of atherosclerosis.https://www.mdpi.com/2073-4409/12/22/2666<i>Monostroma nitidum</i>rhamnan sulfateatherosclerosisApoE-deficient mouse
spellingShingle Masahiro Terasawa
Liqing Zang
Keiichi Hiramoto
Yasuhito Shimada
Mari Mitsunaka
Ryota Uchida
Kaoru Nishiura
Koichi Matsuda
Norihiro Nishimura
Koji Suzuki
Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet
Cells
<i>Monostroma nitidum</i>
rhamnan sulfate
atherosclerosis
ApoE-deficient mouse
title Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet
title_full Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet
title_fullStr Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet
title_full_unstemmed Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet
title_short Oral Administration of Rhamnan Sulfate from <i>Monostroma nitidum</i> Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet
title_sort oral administration of rhamnan sulfate from i monostroma nitidum i suppresses atherosclerosis in apoe deficient mice fed a high fat diet
topic <i>Monostroma nitidum</i>
rhamnan sulfate
atherosclerosis
ApoE-deficient mouse
url https://www.mdpi.com/2073-4409/12/22/2666
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