Abstract
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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a slowly progressive affliction that includes a wide spectrum of liver diseases, ranging from simple fatty liver to nonalcoholic steatohepatitis (NASH); these may eventually progress to liver cirrhosis, and hepatocellular carcinoma [1]
We are the first to investigate the beneficial effects of Gallic acid (GA) administration on nutritional hepatosteatosis via a more holistic approach that uses nuclear magnetic resonance (NMR)-based metabolomics
In order to evaluate the preventive effects of GA on NAFLD, male C57BL/6 mice were subjected to HFD for 16 weeks
Summary
Nonalcoholic fatty liver disease (NAFLD) is a slowly progressive affliction that includes a wide spectrum of liver diseases, ranging from simple fatty liver to nonalcoholic steatohepatitis (NASH); these may eventually progress to liver cirrhosis, and hepatocellular carcinoma [1]. Plant-derived polyphenol compounds possess a wide range of pharmacological properties and their action has been the subject of considerable interest in recent years. GA have been reported to have potent free radical scavenging and antioxidative activities [10,11] and the study of the mechanism of action of GA has received much attention recently. The protective effect of GA on hepatic lipid peroxide metabolism, glycoprotein components and lipid peroxidation in the STZ-induced diabetic rats has been reported [14]. Even though many reports have revealed that GA seems to play an important role in the prevention of diabetes and metabolic disease development, direct evidence of these effects and the mechanism underlying the action of GA on NAFLD remain unclear
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