Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.
Int Immunopharmacol. 2023 Aug;121:110423. doi: 10.1016/j.intimp.2023.110423. Epub 2023 Jun 17.
Eleutheroside E, a major natural bioactive compound in Acanthopanax senticosus (Rupr.etMaxim.) Harms, possesses anti-oxidative, anti-fatigue, anti-inflammatory, anti-bacterial and immunoregulatory effects. High-altitude hypobaric hypoxia affects blood flow and oxygen utilisation, resulting in severe heart injury that cannot be reversed, thereby eventually causing or exacerbating high-altitude heart disease and heart failure. The purpose of this study was to determine the cardioprotective effects of eleutheroside E against high-altitude-induced heart injury (HAHI), and to study the mechanisms by which this happens. A hypobaric hypoxia chamber was used in the study to simulate hypobaric hypoxia at the high altitude of 6000 m. 42 male rats were randomly assigned to 6 equal groups and pre-treated with saline, eleutheroside E 100 mg/kg, eleutheroside E 50 mg/kg, or nigericin 4 mg/kg. Eleutheroside E exhibited significant dose-dependent effects on a rat model of HAHI by suppressing inflammation and pyroptosis. Eleutheroside E downregulated the expressions of brain natriuretic peptide (BNP), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH). Moreover, The ECG also showed eleutheroside E improved the changes in QT interval, corrected QT interval, QRS interval and heart rate. Eleutheroside E remarkably suppressed the expressions of NLRP3/caspase-1-related proteins and pro-inflammatory factors in heart tissue of the model rats. Nigericin, known as an agonist of NLRP3 inflammasome-mediated pyroptosis, reversed the effects of eleutheroside E. Eleutheroside E prevented HAHI and inhibited inflammation and pyroptosis via the NLRP3/caspase-1 signalling pathway. Taken together, eleutheroside E is a prospective, effective, safe and inexpensive agent that can be used to treat HAHI.
刺五加苷 E 是刺五加（Rupr.etMaxim.）中的一种主要天然生物活性化合物，具有抗氧化、抗疲劳、抗炎、抗菌和免疫调节作用。高空低氧环境会影响血流和氧气利用，导致严重的心脏损伤且无法逆转，从而最终导致或加重高原心脏病和心力衰竭。本研究旨在探讨刺五加苷 E 对高原诱导的心脏损伤（HAHI）的心脏保护作用，并研究其作用机制。本研究采用低压缺氧舱模拟 6000 米高空的低压缺氧环境。42 只雄性大鼠随机分为 6 组，分别给予生理盐水、刺五加苷 E 100mg/kg、刺五加苷 E 50mg/kg 或 Nigericin 4mg/kg 预处理。刺五加苷 E 对 HAHI 大鼠模型具有显著的剂量依赖性作用，可抑制炎症和细胞焦亡。刺五加苷 E 下调脑钠肽（BNP）、肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）的表达。此外，心电图也显示刺五加苷 E 改善了 QT 间期、校正 QT 间期、QRS 间期和心率的变化。刺五加苷 E 显著抑制了模型大鼠心脏组织中 NLRP3/caspase-1 相关蛋白和促炎因子的表达。Nigericin 是 NLRP3 炎性小体介导的细胞焦亡的激动剂，可逆转刺五加苷 E 的作用。刺五加苷 E 通过 NLRP3/caspase-1 信号通路预防 HAHI 并抑制炎症和细胞焦亡。综上所述，刺五加苷 E 是一种有前景、有效、安全且廉价的治疗 HAHI 的药物。
