Cargando…
Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice
Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti‐inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulator...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810944/ https://www.ncbi.nlm.nih.gov/pubmed/33241629 http://dx.doi.org/10.1111/jcmm.16106 |
_version_ | 1783637404471525376 |
---|---|
author | Wu, Yao Song, Fei Li, Yunda Li, Jingzhou Cui, Yukai Hong, Yixiang Han, Weimin Wu, Weiyin Lakhani, Ishan Li, Gang Wang, Yan |
author_facet | Wu, Yao Song, Fei Li, Yunda Li, Jingzhou Cui, Yukai Hong, Yixiang Han, Weimin Wu, Weiyin Lakhani, Ishan Li, Gang Wang, Yan |
author_sort | Wu, Yao |
collection | PubMed |
description | Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti‐inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE(−/−)) mice. Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non‐induced by human oxidized low‐density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE(−/−) mice were fed either a Western diet or a chow diet. Acacetin pro‐drug (15 mg/kg) was injected subcutaneously two times a day for 12 weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3 μmol/L. Moreover, 3 μmol/L acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo, acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet‐fed apoE(−/−) mice. Our findings demonstrate the anti‐oxidative and anti‐atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic‐related cardiovascular diseases (CVD). |
format | Online Article Text |
id | pubmed-7810944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78109442021-01-22 Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice Wu, Yao Song, Fei Li, Yunda Li, Jingzhou Cui, Yukai Hong, Yixiang Han, Weimin Wu, Weiyin Lakhani, Ishan Li, Gang Wang, Yan J Cell Mol Med Original Articles Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti‐inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE(−/−)) mice. Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non‐induced by human oxidized low‐density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE(−/−) mice were fed either a Western diet or a chow diet. Acacetin pro‐drug (15 mg/kg) was injected subcutaneously two times a day for 12 weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3 μmol/L. Moreover, 3 μmol/L acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo, acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet‐fed apoE(−/−) mice. Our findings demonstrate the anti‐oxidative and anti‐atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic‐related cardiovascular diseases (CVD). John Wiley and Sons Inc. 2020-11-26 2021-01 /pmc/articles/PMC7810944/ /pubmed/33241629 http://dx.doi.org/10.1111/jcmm.16106 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wu, Yao Song, Fei Li, Yunda Li, Jingzhou Cui, Yukai Hong, Yixiang Han, Weimin Wu, Weiyin Lakhani, Ishan Li, Gang Wang, Yan Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice |
title | Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice |
title_full | Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice |
title_fullStr | Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice |
title_full_unstemmed | Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice |
title_short | Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE(−/−) Mice |
title_sort | acacetin exerts antioxidant potential against atherosclerosis through nrf2 pathway in apoe(−/−) mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810944/ https://www.ncbi.nlm.nih.gov/pubmed/33241629 http://dx.doi.org/10.1111/jcmm.16106 |
work_keys_str_mv | AT wuyao acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT songfei acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT liyunda acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT lijingzhou acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT cuiyukai acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT hongyixiang acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT hanweimin acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT wuweiyin acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT lakhaniishan acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT ligang acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice AT wangyan acacetinexertsantioxidantpotentialagainstatherosclerosisthroughnrf2pathwayinapoemice |