Shen Zherui, Huang Demei, Jia Nan, Zhao Sijing, Pei Caixia, Wang Yilan, Wu Yongcan, Wang Xiaomin, Shi Shihua, Wang Fei, He Yacong, Wang Zhenxing
Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Chongqing Medical University, Chongqing 400016, China.
Biomed Pharmacother. 2023 Nov;167:115607. doi: 10.1016/j.biopha.2023.115607. Epub 2023 Sep 28.
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.
刺五加苷E（EE）是刺五加的主要活性成分，据报道它能抑制炎症基因的表达，但其潜在机制仍不清楚。高原肺水肿（HAPE）是海拔2500米以上高原暴露后的一种严重并发症。然而，针对HAPE的有效且安全的预防措施仍有待改进。本研究旨在阐明EE对HAPE的预防潜力及其潜在机制。通过低压低氧建立HAPE大鼠模型。从机制上讲，低压低氧会加剧氧化应激并上调（促）炎细胞因子，激活NOD样受体蛋白3（NLRP3）炎性小体介导的细胞焦亡，最终导致HAPE。EE通过抑制核因子κB（NF-κB）的核转位来抑制NLRP3炎性小体介导的细胞焦亡，从而保护肺部免受HAPE侵害。然而，NLRP3激活剂尼日利亚菌素（Nig）部分消除了EE的保护作用。这些发现表明，EE是预防NLRP3炎性小体介导的细胞焦亡所致HAPE的一种有前景的药物。
