Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
Economic and Technological Development Zone, Jiangsu Kanion Pharmaceutical Co., Ltd, Jiangning Industrial City, Lianyungang Jiangsu 222001, China.
Phytomedicine. 2022 Sep;104:154337. doi: 10.1016/j.phymed.2022.154337. Epub 2022 Jul 12.
An overdose of acetaminophen (APAP), the main cause of acute liver failure (ALF), induces oxidative stress that ultimately causes mitochondrial impairment and hepatotoxicity. The nuclear factor erythroid 2-related factor 2 (Nrf2) was widely recognized as an anti-oxidative stress mechanism. The present study was aimed at investigating whether sarmentosin, extract from traditional Chinese medicine, protects the liver against APAP-induced injury via activating Nrf2 and subsequently decreasing oxidative stress.
Male ICR mice were treated with sarmentosin oral administration for 1 week and injected APAP (300 mg/kg. i.p.) for acute liver injury model. The liver and serum of mice for histological and biochemistry analysis. AML12 and LO2 cells were used in vitro assays.
We found that sarmentosin moderately increased accumulation of Nrf2 via upregulating USP17-mediated ubiquitin inhibition at the early stage of hepatocytes damage. The Nrf2 separating from bonding protein Keap1 translocated into nucleus and activated downstream gene of antioxidants. Mitophagy, a unique autophagy can remove Reactive Oxygen Species (ROS) damaged mitochondria, was elevated in this progress to maintain mitochondria function and ROS homeostasis.
In summary, our research revealed that sarmentosin could alleviate APAP-induced liver acute injury through USP17-mediated Nrf2 overexpression and PINK1-dependent mitophagy.
对乙酰氨基酚（APAP）的过量摄入是急性肝衰竭（ALF）的主要原因，会引起氧化应激，最终导致线粒体损伤和肝毒性。核因子红细胞 2 相关因子 2（Nrf2）被广泛认为是一种抗氧化应激机制。本研究旨在探讨从传统中药中提取的桑枝乙素是否通过激活 Nrf2 并随后降低氧化应激来保护肝脏免受 APAP 诱导的损伤。
雄性 ICR 小鼠经桑枝乙素口服处理 1 周，并用 APAP（300mg/kg，ip）注射建立急性肝损伤模型。对小鼠的肝和血清进行组织学和生化分析。AML12 和 LO2 细胞用于体外检测。
我们发现桑枝乙素通过上调 USP17 介导的泛素抑制作用，在肝细胞损伤的早期适度增加 Nrf2 的积累。与结合蛋白 Keap1 分离的 Nrf2 转位到细胞核并激活抗氧化剂的下游基因。自噬，一种独特的自噬，可以清除 ROS 损伤的线粒体，在这个过程中被上调，以维持线粒体功能和 ROS 平衡。
总之，我们的研究表明，桑枝乙素可以通过 USP17 介导的 Nrf2 过表达和 PINK1 依赖性线粒体自噬来减轻 APAP 诱导的肝急性损伤。
