Abstract Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects. Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism. Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) + iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 ∼ 30 μM) for 1 h before AA + iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP. Results: In vitro, emodin treatment inhibited the cell death induced by AA + iron maximally at a dose of 10 μM (EC50 > 3 μM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 μM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage. Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.

中文翻译：

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大黄中的大黄素通过 AMPK 和 Hippo/Yap 信号通路抑制肝脏氧化应激

摘要背景：大黄素是大黄（蓼科）中的一种化合物，据报道具有抗炎、抗菌和抗过敏作用。目的：氧化应激是肝脏炎症的病原体，可导致纤维化和肝癌。在这项研究中，我们研究了大黄素的抗氧化作用及其机制。材料和方法：我们使用花生四烯酸 (AA) + 铁共处理刺激的肝细胞和 C57B/6 小鼠口服对乙酰氨基酚 (APAP, 500 mg/kg, 6 h)，通过免疫印迹和下一代测序 (NGS) 评估）。大黄素在 AA + 铁之前在肝细胞（3 ∼ 30 μM）中预处理 1 小时，在 APAP 之前在小鼠（10 和 30 m/kg，PO）中预处理 3 天。结果：体外，大黄素处理在 10 μM 的剂量下最大程度地抑制了 AA + 铁诱导的细胞死亡（EC50 > 3 μM）。此外，大黄素减弱了抗凋亡蛋白的减少，并恢复了肝激酶 B1 (LKB1)-AMP 活化蛋白激酶 (AMPK) 通路介导的线粒体膜电位。使用 LKB1 缺陷细胞系 HeLa 验证了 LKB1 介导的 AMPK 激活。大黄素（10 μM；10 分钟后）还诱导 Yes 相关蛋白 1 (YAP1) 的磷酸化，这是 Hippo 信号通路的主要下游靶标，介导氧化应激或 ROS 启动的信号通路。在体内，大黄素（10 和 30 m/kg，3 天）的口服治疗减少了 APAP 诱导的肝损伤，这表现为抗氧化基因和组织损伤的减少。结论：