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

作者全名："Shen, Zherui; Huang, Demei; Jia, Nan; Zhao, Sijing; Pei, Caixia; Wang, Yilan; Wu, Yongcan; Wang, Xiaomin; Shi, Shihua; Wang, Fei; He, Yacong; Wang, Zhenxing"

作者地址："[Shen, Zherui; Huang, Demei; Jia, Nan; Zhao, Sijing; Pei, Caixia; Wang, Yilan; Wang, Xiaomin; Shi, Shihua; Wang, Fei; He, Yacong; Wang, Zhenxing] Chengdu Univ Tradit Chinese Med, Chengdu 610075, Peoples R China; [Wu, Yongcan] Chongqing Med Univ, Chongqing 400016, Peoples R China; [He, Yacong] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu 611137, Peoples R China; [Wang, Fei; Wang, Zhenxing] Chengdu Univ Tradit Chinese Med, 37 Shi Er Qiao Rd, Chengdu 610072, Peoples R China"

通信作者："He, YC (通讯作者)，Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu 611137, Peoples R China.; Wang, F; Wang, ZX (通讯作者)，Chengdu Univ Tradit Chinese Med, 37 Shi Er Qiao Rd, Chengdu 610072, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001091871000001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：167

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Eleutheroside E; High-altitude pulmonary edema; Hypobaric hypoxia; NLRP3 inflammasome; NF-kappa B; Pyroptosis

摘要："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-B (NF-kappa B), 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."

基金机构："National Natural Science Foundation of China [82205043]; China Postdoctoral Science Foundation [2022M710500, YJ20220058]; Sichuan Provincial Administration of Traditional Chinese Medicine [2023MS555]"

基金资助正文："<B>Funding</B> This research was financially supported by National Natural Science Foundation of China (No. 82205043) , China Postdoctoral Science Foundation (No. 2022M710500 and No. YJ20220058) and Sichuan Provincial Administration of Traditional Chinese Medicine (No. 2023MS555) ."