Aloin protects mice from diet-induced non-alcoholic steatohepatitis via activation of Nrf2/HO-1 signaling.
Aloin protects mice from diet-induced non-alcoholic steatohepatitis via activation of Nrf2/HO-1 signaling.
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DOI：
10.1039/d0fo02684k
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发表时间：
2021-01
期刊：
影响因子：
6.1
通讯作者：
Qiushi Xu;Yunhui Fan;J. Loor;Yusheng Liang;Hongming Lv;Xudong Sun;Hongdou Jia;Chuang Xu
中科院分区：
文献类型：
--
作者：
Qiushi Xu;Yunhui Fan;J. Loor;Yusheng Liang;Hongming Lv;Xudong Sun;Hongdou Jia;Chuang Xu
芦荟苷是一种天然存在的蒽醌苷，来源于芦荟属植物，具有抗氧化和抗炎活性，但其在非酒精性脂肪性肝炎（NASH）中的作用尚不清楚。本研究旨在探讨芦荟素在NASH中的抗炎、抗氧化和抗凋亡作用及其机制。给野生型或核红细胞2相关因子2（Nrf 2）敲除（KO）小鼠喂食胆碱缺乏、l-氨基酸限定的高脂肪（CDAAH）饮食，并通过管饲法用芦荟苷（10、20或40 mg/kg bw/天）处理12周。采集肝脏和血液样本以评价肝功能、蛋白丰度和组织病理学状态。以20 mg kg-1补充芦荟素对于减轻NASH期间的肝损伤是最佳的，如血清中丙氨酸转氨酶和天冬氨酸转氨酶活性降低所证明的。芦荟素的补充显著降低了血清中丙二醛、肿瘤坏死因子α、白细胞介素（IL）-1β和IL-6的浓度或肝脏蛋白丰度。芦荟苷治疗增强NASH小鼠肝脏超氧化物歧化酶活性、谷胱甘肽和血清IL-10水平。此外，芦荟素的补充抑制Bcl-2上调和切割的caspase-3和Bax下调引起的肝细胞凋亡。从机制上讲，通过使用Nrf 2 KO小鼠，芦荟素的保护作用与增强的抗氧化、抗炎和抗凋亡活性相关，所有这些都是由Nrf 2/血红素加氧酶-1（HO-1）信号转导激活介导的。数据表明，芦荟素激活Nrf 2/HO-1通路，并对NASH期间的肝损伤具有保护潜力。因此，芦荟素补充剂可能有助于通过激活Nrf 2/HO-1途径预防和治疗NASH。
Aloin, a naturally occurring anthraquinone glycoside derived from the Aloe species, has antioxidant and anti-inflammatory activities, but its role in non-alcoholic steatohepatitis (NASH) remains unknown. This study was designed to investigate the anti-inflammatory, antioxidant, and anti-apoptotic effects of aloin and the underlying mechanisms during NASH. Wild-type or nuclear erythroid 2-related factor 2 (Nrf2) knock-out (KO) mice were fed a choline-deficient, l-amino acid-defined, high-fat (CDAAH) diet and treated with aloin (10, 20 or 40 mg per kg bw per day) by gavage for twelve weeks. Liver and blood samples were collected to evaluate liver function, protein abundance, and histopathological status. Supplementing aloin at 20 mg kg-1 was optimal for mitigating liver damage during NASH, as evidenced by reduced alanine transaminase and aspartate aminotransferase activity in serum. Supplementation with aloin significantly reduced serum concentration or liver protein abundance of malondialdehyde, tumor necrosis factor alpha, Interleukin (IL)-1β and IL-6. Aloin treatment enhanced hepatic superoxide dismutase activity, glutathione and serum IL-10 levels in mice with NASH. Furthermore, supplementation with aloin inhibited hepatocyte apoptosis caused by Bcl-2 up-regulation and cleaved caspase-3 and Bax down-regulation. Mechanistically, by using Nrf2 KO mice, the protective effects of aloin were associated with enhanced antioxidant, anti-inflammatory and anti-apoptotic activity, all of which were mediated by Nrf2/heme oxygenase-1 (HO-1) signaling activation. Data suggested that aloin activates the Nrf2/HO-1 pathway and has protective potential against liver injury during NASH. Therefore, aloin supplementation might contribute to the prevention and treatment of NASH via activation of the Nrf2/HO-1 pathway.