Protective effects of Eleutheroside E against high-altitude pulmonary edema by inhibiting NLRP3 inflammasome-mediated pyroptosis

Zherui Shen; Demei Huang; Nan Jia; Sijing Zhao; Caixia Pei; Yilan Wang; Yongcan Wu; Xiaomin Wang; Shihua Shi; Fei Wang; Yacong He; Zhenxing Wang

doi:10.1016/j.biopha.2023.115607

Protective effects of Eleutheroside E against high-altitude pulmonary edema by inhibiting NLRP3 inflammasome-mediated pyroptosis

Biomed Pharmacother. 2023 Nov:167:115607. doi: 10.1016/j.biopha.2023.115607. Epub 2023 Sep 28.

Authors

Zherui Shen¹, Demei Huang¹, Nan Jia¹, Sijing Zhao¹, Caixia Pei¹, Yilan Wang¹, Yongcan Wu², Xiaomin Wang¹, Shihua Shi¹, Fei Wang³, Yacong He⁴, Zhenxing Wang⁵

Affiliations

¹ Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
² Chongqing Medical University, Chongqing 400016, China.
³ Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. Electronic address: wangfei@cdutcm.edu.cn.
⁴ Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: heyacong@cdutcm.edu.cn.
⁵ Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. Electronic address: wangzhenxing@cdutcm.edu.cn.

PMID: 37776644
DOI: 10.1016/j.biopha.2023.115607

Abstract

Eleutheroside E (EE) is a primary active component of Acanthopanax senticosus, which has been reported to inhibit the expression of inflammatory genes, but the underlying mechanisms remain elusive. High-altitude pulmonary edema (HAPE) is a severe complication of high-altitude exposure occurring after ascent above 2500 m. However, effective and safe preventative measures for HAPE still need to be improved. This study aimed to elucidate the preventative potential and underlying mechanism of EE in HAPE. Rat models of HAPE were established through hypobaric hypoxia. Mechanistically, hypobaric hypoxia aggravates oxidative stress and upregulates (pro)-inflammatory cytokines, activating NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis, eventually leading to HAPE. EE suppressed NLRP3 inflammasome-mediated pyroptosis by inhibiting the nuclear translocation of nuclear factor kappa-Β (NF-κB), thereby protecting the lung from HAPE. However, nigericin (Nig), an NLRP3 activator, partially abolished the protective effects of EE. These findings suggest EE is a promising agent for preventing HAPE induced by NLRP3 inflammasome-mediated pyroptosis.

Keywords: Eleutheroside E; High-altitude pulmonary edema; Hypobaric hypoxia; NF-κB; NLRP3 inflammasome; Pyroptosis.