Cyasterone ameliorates sepsis-related acute lung injury via AKT (Ser473)/GSK3β (Ser9)/Nrf2 pathway

Chinese Medicine

Research

Lu Ren¹  Xiaoting Huang²  Rui Qian²  Wei Liu²  Lang Deng²  Dayan Xiong²  Xiaoxue Sang²  Qingzhong Hua²  Miao Lin²  Yuyang Luo²  Qian Zeng²  Weixi Xie²  Siyuan Tang²  Tingting Zhou²  Xiaohua Zhang³  Lei Huang³ 

[1] Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, 410013, Changsha, China;Department of Community Nursing, Xiangya Nursing School, Central South University, 410013, Changsha, China;Occupational Disease Department, Hunan Prevention and Treatment Institute for Occupational Diseases, 410013, Changsha, China;

关键词: Cyasterone;    Acute lung injury;    Inflammation;    Oxidative stress;    Nrf2;    AKT;   

DOI  :  10.1186/s13020-023-00837-2

 received in 2023-06-13, accepted in 2023-09-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAcute 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.MethodsWe 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.ResultsCyasterone 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.ConclusionsCyasterone 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.

【 授权许可】

CC BY   
© International Society for Chinese Medicine and BioMed Central Ltd. 2023

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