Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress.
Protective Effects of Alisma orientale Extract against Hepatic Steatosis via Inhibition of Endoplasmic Reticulum Stress.
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DOI：
10.3390/ijms161125944
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发表时间：
2015-11-02
影响因子：
5.6
通讯作者：
Jung MH
中科院分区：
文献类型：
--
作者：
Jang MK;Han YR;Nam JS;Han CW;Kim BJ;Jeong HS;Ha KT;Jung MH
内质网应激与肝脂肪变性的发病机制有关。泽泻是利尿剂、糖尿病、肝炎和炎症的传统草药。本研究在体外和体内研究了泽泻块茎（MEAO）甲醇提取物对内质酶应激诱导的肝脏脂肪变性的保护作用。MEAO抑制了tunicamycin诱导的含有内质网应激反应元件和ATF6应激反应元件的内质网应激报告结构体荧光素酶活性的升高。在tunicamycin处理的人肝癌（HepG2）细胞和tunicamycin注射小鼠肝脏中，MEAO显著抑制tunicamycin诱导的内质网应激标志物GRP78、CHOP和XBP-1的表达。它还能抑制tunicamycin诱导的细胞甘油三酯的积累。在生理内质网应激条件下，如棕榈酸酯（PA）处理的HepG2细胞和高脂饮食（HFD）诱导的肥胖小鼠的肝脏中，也进行了类似的观察。MEAO抑制pa处理的HepG2细胞和HFD肥胖小鼠肝脏的脂肪生成基因表达。此外，MEAO抑制了tunicamycin注射小鼠或HFD肥胖小鼠肝脏以及tunicamycin或pa处理的HepG2细胞中极低密度脂蛋白受体（VLDLR）的表达，并改善了ApoB的分泌。在tunicamycin处理的HepG2细胞中，Alismol（泽泻中一种愈蓝烷型倍半萜）抑制GRP78的表达。综上所述，MEAO通过抑制肝脏脂肪生成基因和VLDLR的表达以及增强ApoB的分泌来减轻内质网应激，防止肝脏脂肪变性的发生。
Endoplasmic reticulum (ER) stress is associated with the pathogenesis of hepatic steatosis. Alisma orientale Juzepzuk is a traditional medicinal herb for diuretics, diabetes, hepatitis, and inflammation. In this study, we investigated the protective effects of methanol extract of the tuber of Alisma orientale (MEAO) against ER stress-induced hepatic steatosis in vitro and in vivo. MEAO inhibited the tunicamycin-induced increase in luciferase activity of ER stress-reporter constructs containing ER stress response element and ATF6 response element. MEAO significantly inhibited tunicamycin-induced ER stress marker expression including GRP78, CHOP, and XBP-1 in tunicamycin-treated Human hepatocellular carcinoma (HepG2) cells and the livers of tunicamycin-injected mice. It also inhibited tunicamycin-induced accumulation of cellular triglyceride. Similar observations were made under physiological ER stress conditions such as in palmitate (PA)-treated HepG2 cells and the livers of high-fat diet (HFD)-induced obese mice. MEAO repressed hepatic lipogenic gene expression in PA-treated HepG2 cells and the livers of HFD obese mice. Furthermore, MEAO repressed very low-density lipoprotein receptor (VLDLR) expression and improved ApoB secretion in the livers of tunicamycin-injected mice or HFD obese mice as well as in tunicamycin or PA-treated HepG2 cells. Alismol, a guaiane-type sesquiterpenes in Alisma orientale, inhibited GRP78 expression in tunicamycin-treated HepG2 cells. In conclusion, MEAO attenuates ER stress and prevents hepatic steatosis pathogenesis via inhibition of expression of the hepatic lipogenic genes and VLDLR, and enhancement of ApoB secretion.