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Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway
BACKGROUND: Acute lung injury (ALI) is a severe disease that can lead to acute respiratory distress syndrome (ARDS), characterized by intractable hypoxemia, poor lung compliance, and respiratory failure, severely affecting patients' quality of life. The pathogenesis of ALI has not been fully el...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585798/ https://www.ncbi.nlm.nih.gov/pubmed/37853474 http://dx.doi.org/10.1186/s13020-023-00837-2 |
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author | Lin, Miao Xie, Weixi Xiong, Dayan Tang, Siyuan Huang, Xiaoting Deng, Lang Huang, Lei Zhang, Xiaohua Zhou, Tingting Qian, Rui Zeng, Qian Sang, Xiaoxue Luo, Yuyang Hua, Qingzhong Ren, Lu Liu, Wei |
author_facet | Lin, Miao Xie, Weixi Xiong, Dayan Tang, Siyuan Huang, Xiaoting Deng, Lang Huang, Lei Zhang, Xiaohua Zhou, Tingting Qian, Rui Zeng, Qian Sang, Xiaoxue Luo, Yuyang Hua, Qingzhong Ren, Lu Liu, Wei |
author_sort | Lin, Miao |
collection | PubMed |
description | BACKGROUND: Acute lung injury (ALI) is a severe disease that can lead to acute respiratory distress syndrome (ARDS), characterized by intractable hypoxemia, poor lung compliance, and respiratory failure, severely affecting patients' quality of life. The pathogenesis of ALI has not been fully elucidated yet, and sepsis is an important cause of ALI. Among the organ injuries caused by sepsis, the lungs are the earliest damaged ones. Radix cyathulae is reported to have analgesic, anti-inflammatory, and anti-aging effects. Cyasterone is extracted from Radix cyathulae. However, it is not known whether cyasterone has protective effects for ALI. This study aims to investigate the effect of cyasterone on sepsis-related ALI and its mechanism. METHODS: We used the cecal ligation peferation (CLP) method to establish a mouse sepsis model, and cyasterone was given intraperitoneally on days 1–3 to observe its preventive effect on sepsis-related acute lung injury. Primary murine peritoneal macrophages were used to investigate the molecular mechanism of cyasterone in vitro. RESULTS: Cyasterone pretreatment inhibits pro-inflammatory cytokine production, NLRP3 inflammasome activation, and oxidative stress in vivo and in vitro. In addition, cyasterone attenuates sepsis-induced ALI by activating nuclear factor erythroid2-related factor (Nrf2), which may be associated with AKT(Ser473)/GSK3β(Ser9) pathway activation. CONCLUSIONS: Cyasterone defends against sepsis-induced ALI by inhibiting inflammatory responses and oxidative stress, which depends heavily on the upregulation of the Nrf2 pathway through phosphorylation of AKT(Ser473)/GSK3β(Ser9). These results suggest cyasterone may be a valuable drug candidate for preventing sepsis-related ALI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-023-00837-2. |
format | Online Article Text |
id | pubmed-10585798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105857982023-10-20 Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway Lin, Miao Xie, Weixi Xiong, Dayan Tang, Siyuan Huang, Xiaoting Deng, Lang Huang, Lei Zhang, Xiaohua Zhou, Tingting Qian, Rui Zeng, Qian Sang, Xiaoxue Luo, Yuyang Hua, Qingzhong Ren, Lu Liu, Wei Chin Med Research BACKGROUND: Acute lung injury (ALI) is a severe disease that can lead to acute respiratory distress syndrome (ARDS), characterized by intractable hypoxemia, poor lung compliance, and respiratory failure, severely affecting patients' quality of life. The pathogenesis of ALI has not been fully elucidated yet, and sepsis is an important cause of ALI. Among the organ injuries caused by sepsis, the lungs are the earliest damaged ones. Radix cyathulae is reported to have analgesic, anti-inflammatory, and anti-aging effects. Cyasterone is extracted from Radix cyathulae. However, it is not known whether cyasterone has protective effects for ALI. This study aims to investigate the effect of cyasterone on sepsis-related ALI and its mechanism. METHODS: We used the cecal ligation peferation (CLP) method to establish a mouse sepsis model, and cyasterone was given intraperitoneally on days 1–3 to observe its preventive effect on sepsis-related acute lung injury. Primary murine peritoneal macrophages were used to investigate the molecular mechanism of cyasterone in vitro. RESULTS: Cyasterone pretreatment inhibits pro-inflammatory cytokine production, NLRP3 inflammasome activation, and oxidative stress in vivo and in vitro. In addition, cyasterone attenuates sepsis-induced ALI by activating nuclear factor erythroid2-related factor (Nrf2), which may be associated with AKT(Ser473)/GSK3β(Ser9) pathway activation. CONCLUSIONS: Cyasterone defends against sepsis-induced ALI by inhibiting inflammatory responses and oxidative stress, which depends heavily on the upregulation of the Nrf2 pathway through phosphorylation of AKT(Ser473)/GSK3β(Ser9). These results suggest cyasterone may be a valuable drug candidate for preventing sepsis-related ALI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-023-00837-2. BioMed Central 2023-10-19 /pmc/articles/PMC10585798/ /pubmed/37853474 http://dx.doi.org/10.1186/s13020-023-00837-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lin, Miao Xie, Weixi Xiong, Dayan Tang, Siyuan Huang, Xiaoting Deng, Lang Huang, Lei Zhang, Xiaohua Zhou, Tingting Qian, Rui Zeng, Qian Sang, Xiaoxue Luo, Yuyang Hua, Qingzhong Ren, Lu Liu, Wei Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway |
title | Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway |
title_full | Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway |
title_fullStr | Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway |
title_full_unstemmed | Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway |
title_short | Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway |
title_sort | cyasterone ameliorates sepsis-related acute lung injury via akt (ser473)/gsk3β (ser9)/nrf2 pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585798/ https://www.ncbi.nlm.nih.gov/pubmed/37853474 http://dx.doi.org/10.1186/s13020-023-00837-2 |
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