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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
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 |