Eleutheroside B ameliorated high altitude pulmonary edema by attenuating ferroptosis and necroptosis through Nrf2-antioxidant response signaling

High altitude pulmonary edema (HAPE) is a potentially fatal condition induced by exposure to high-altitude environment. Eleutheroside B is a naturally active polyphenolic substance that has previously demonstrated anti-inflammatory, antioxidant and antidepressant properties. However, the effects of...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2022-12, Vol.156, p.113982-113982, Article 113982
Main Authors: Wang, Yilan, Shen, Zherui, Pei, Caixia, Zhao, Sijing, Jia, Nan, Huang, Demei, Wang, Xiaomin, Wu, Yongcan, Shi, Shihua, He, Yacong, Wang, Zhenxing
Format: Article
Language:English
Subjects:
Eleutheroside B
Ferroptosis
High-altitude pulmonary edema
Necroptosis
Nrf2
Oxidative stress
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Summary:High altitude pulmonary edema (HAPE) is a potentially fatal condition induced by exposure to high-altitude environment. Eleutheroside B is a naturally active polyphenolic substance that has previously demonstrated anti-inflammatory, antioxidant and antidepressant properties. However, the effects of eleutheroside B on HPAE are unknown. Here, eleutheroside B (50 mg/kg and 100 mg/kg) was applied to HAPE rats. Eleutheroside B alleviated lung edema and decreased levels of tumor necrosis factor-α, interleukin-1β, vascular endothelial growth factor, and total proteins in the bronchoalveolar lavage fluid. Eleutheroside B reversed the acid-base disturbances by HAPE. In addition, eleutheroside B reversed the oxidative stress. Eleutheroside B pretreatment facilitated the translocation of nuclear factor E2-related factor 2 (Nrf2) into the nucleus, contributing to the inhibition of ferroptosis and necroptosis. ML385 confirmed the role of Nrf2 in ferroptosis and necroptosis. Collectively, the beneficial effects of eleutheroside B against HAPE were associated with the inhibition of ferroptosis and necroptosis through Nrf2-antioxidant response signaling. [Display omitted] •Exposure to high altitude altered the nuclear translocation of Nrf2.•Eleutheroside B facilitated Nrf2 translocation to the nucleus in HAPE.•Eleutheroside B inhibited oxidative stress, ferroptosis and necroptosis by activating the nuclear translocation of Nrf2.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2022.113982