Qin Xian-Yang, Su Ting, Kojima Soichi
Liver Cancer Prevention Research Unit, RIKEN Center for Integrative Medical Sciences, Wako, Saitama 351-0198, Japan.
Exp Ther Med. 2020 Feb;19(2):1522-1527. doi: 10.3892/etm.2019.8384. Epub 2019 Dec 27.
Garlic and its sulfur constituents have numerous biological functions, such as antioxidant, anti-inflammatory, anti-microbial, anticancer, antidiabetic and cardioprotective effects. Fatty liver diseases, such as non-alcoholic steatohepatitis, which is characterized by the accumulation of lipids and oxidative stress in hepatocytes and continual liver damage, has attracted much attention, and it is believed that it will become the leading etiology of liver cancer. We have previously reported that the growth-suppressive effects of arachidonic acid (AA), an unsaturated fatty acid known to be a pro-inflammatory precursor, is accompanied by the production of reactive oxygen species followed by the nuclear accumulation and activation of the protein crosslinking enzyme, transglutaminase (TG)2. In this study, we examined the potential role of garlic extracts in preventing the growth-suppressive effects of AA on human hepatic cells. We also aimed to provide a mechanistic insight regarding the association between the hepatoprotective effects of garlic extract and the inhibition of the TG-related crosslinking of nuclear proteins, which is not associated with hepatic lipid partitioning mediated by stearoyl-CoA desaturase-1. Given the critical roles of unsaturated fatty acids in the regulation of cancer cell stemness and immune surveillance in the context of chronic injury, we propose that garlic extracts may serve as a therapeutic option for the prevention of chronic liver injury and inflammation, as well as for the prevention of the carcinogenesis of fatty livers.
大蒜及其含硫成分具有多种生物学功能，如抗氧化、抗炎、抗菌、抗癌、抗糖尿病和心脏保护作用。脂肪肝疾病，如非酒精性脂肪性肝炎，其特征是肝细胞中脂质积累和氧化应激以及持续的肝损伤，已引起广泛关注，并且人们认为它将成为肝癌的主要病因。我们之前报道过，花生四烯酸（AA）是一种已知的促炎前体不饱和脂肪酸，其生长抑制作用伴随着活性氧的产生，随后是蛋白质交联酶转谷氨酰胺酶（TG）2的核积累和激活。在本研究中，我们研究了大蒜提取物在预防AA对人肝细胞生长抑制作用方面的潜在作用。我们还旨在提供一个关于大蒜提取物的肝脏保护作用与抑制TG相关的核蛋白交联之间关联的机制性见解，这与硬脂酰辅酶A去饱和酶-1介导的肝脏脂质分配无关。鉴于不饱和脂肪酸在慢性损伤背景下对癌细胞干性调节和免疫监视的关键作用，我们提出大蒜提取物可能作为预防慢性肝损伤和炎症以及预防脂肪肝癌变的一种治疗选择。
