Chao Jung, Huo Teh-Ia, Cheng Hao-Yuan, Tsai Jen-Chieh, Liao Jiunn-Wang, Lee Meng-Shiou, Qin Xue-Mei, Hsieh Ming-Tsuen, Pao Li-Heng, Peng Wen-Huang
Institute of Pharmacology, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
Institute of Pharmacology, College of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
PLoS One. 2014 Jun 11;9(2):e96969. doi: 10.1371/journal.pone.0096969. eCollection 2014.
Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.
没食子酸（GA）是一种在蔬菜和水果中天然大量存在的植物酚类化合物，已被证明具有强大的抗氧化和抗肥胖活性。然而，GA对非酒精性脂肪性肝病（NAFLD）的影响尚不清楚。在本研究中，我们采用一种更“全面的视角”方法，即基于1H NMR的代谢组学，研究GA给药对营养性肝脂肪变性模型的有益作用，以证明其疗效，并获取可能有助于更好理解GA作用模式的信息。将雄性C57BL/6小鼠分别置于正常饲料饮食、高脂肪饮食（HFD，60%）或补充GA（50和100mg/kg/天，口服）的高脂肪饮食中16周。肝脏组织病理学和血清生化检查表明，每日给予GA可预防HFD诱导的NAFLD小鼠的肝脂肪变性、肥胖、高胆固醇血症和胰岛素抵抗。此外，偏最小二乘判别分析得分图显示，喂食HFD的小鼠群与正常组小鼠图明显分开，表明这两组的代谢特征明显不同。具体而言，GA处理的小鼠更接近正常组小鼠，表明GA处理部分逆转了HFD引起的代谢谱紊乱。我们的结果表明，GA的肝保护作用部分是通过逆转HFD对一系列代谢途径造成的紊乱而实现的，这些代谢途径包括脂质代谢、葡萄糖代谢（糖酵解和糖异生）、氨基酸代谢、胆碱代谢和肠道微生物群相关代谢。综上所述，本研究表明基于1H NMR的代谢组学方法是天然产物功能评价的有用平台。所选代谢物可能作为预防作用生物标志物，也可用于帮助我们进一步了解GA在肝脂肪变性小鼠中的作用。
