Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.

Celastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxL...

Full description

Bibliographic Details
Main Authors: Lei Gu, Wenli Bai, Sha Li, Yuqing Zhang, Yi Han, Yue Gu, Guoliang Meng, Liping Xie, Jing Wang, Yujiao Xiao, Liyang Shan, Suming Zhou, Lei Wei, Albert Ferro, Yong Ji
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3684610?pdf=render
_version_ 1818519146007101440
author Lei Gu
Wenli Bai
Sha Li
Yuqing Zhang
Yi Han
Yue Gu
Guoliang Meng
Liping Xie
Jing Wang
Yujiao Xiao
Liyang Shan
Suming Zhou
Lei Wei
Albert Ferro
Yong Ji
author_facet Lei Gu
Wenli Bai
Sha Li
Yuqing Zhang
Yi Han
Yue Gu
Guoliang Meng
Liping Xie
Jing Wang
Yujiao Xiao
Liyang Shan
Suming Zhou
Lei Wei
Albert Ferro
Yong Ji
author_sort Lei Gu
collection DOAJ
description Celastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxLDL) induced oxidative stress in RAW 264.7 cells. In addition, the effect of celastrol on atherosclerosis in vivo was assessed in apolipoprotein E knockout (apoE(-/-)) mouse fed a high-fat/high-cholesterol diet (HFC). We found that celastrol significantly attenuated oxLDL-induced excessive expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) and generation of reactive oxygen species (ROS) in cultured RAW264.7 macrophages. Celastrol also decreased IκB phosphorylation and degradation and reduced production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6. Celastrol reduced atherosclerotic plaque size in apoE(-/-) mice. The expression of LOX-1 within the atherosclerotic lesions and generation of superoxide in mouse aorta were also significantly reduced by celastrol while the lipid profile was not improved. In conclusion, our results show that celastrol inhibits atherosclerotic plaque developing in apoE(-/-) mice via inhibiting LOX-1 and oxidative stress.
first_indexed 2024-12-11T01:19:57Z
format Article
id doaj.art-cfa4c202f2f54aebb8c098c7b1d88e18
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-11T01:19:57Z
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-cfa4c202f2f54aebb8c098c7b1d88e182022-12-22T01:25:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6547710.1371/journal.pone.0065477Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.Lei GuWenli BaiSha LiYuqing ZhangYi HanYue GuGuoliang MengLiping XieJing WangYujiao XiaoLiyang ShanSuming ZhouLei WeiAlbert FerroYong JiCelastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxLDL) induced oxidative stress in RAW 264.7 cells. In addition, the effect of celastrol on atherosclerosis in vivo was assessed in apolipoprotein E knockout (apoE(-/-)) mouse fed a high-fat/high-cholesterol diet (HFC). We found that celastrol significantly attenuated oxLDL-induced excessive expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) and generation of reactive oxygen species (ROS) in cultured RAW264.7 macrophages. Celastrol also decreased IκB phosphorylation and degradation and reduced production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6. Celastrol reduced atherosclerotic plaque size in apoE(-/-) mice. The expression of LOX-1 within the atherosclerotic lesions and generation of superoxide in mouse aorta were also significantly reduced by celastrol while the lipid profile was not improved. In conclusion, our results show that celastrol inhibits atherosclerotic plaque developing in apoE(-/-) mice via inhibiting LOX-1 and oxidative stress.http://europepmc.org/articles/PMC3684610?pdf=render
spellingShingle Lei Gu
Wenli Bai
Sha Li
Yuqing Zhang
Yi Han
Yue Gu
Guoliang Meng
Liping Xie
Jing Wang
Yujiao Xiao
Liyang Shan
Suming Zhou
Lei Wei
Albert Ferro
Yong Ji
Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
PLoS ONE
title Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
title_full Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
title_fullStr Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
title_full_unstemmed Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
title_short Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
title_sort celastrol prevents atherosclerosis via inhibiting lox 1 and oxidative stress
url http://europepmc.org/articles/PMC3684610?pdf=render
work_keys_str_mv AT leigu celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT wenlibai celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT shali celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT yuqingzhang celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT yihan celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT yuegu celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT guoliangmeng celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT lipingxie celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT jingwang celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT yujiaoxiao celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT liyangshan celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT sumingzhou celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT leiwei celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT albertferro celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress
AT yongji celastrolpreventsatherosclerosisviainhibitinglox1andoxidativestress