Abstract
Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of β-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.
Highlights
Diabetes is a multi-etiological chronic metabolic disorder that is primarily characterized by pathological and physiological changes induced by insulin resistance and impaired insulin secretion
This study aimed to investigate the beneficial effects of gallic acid (GA) on diabetes and nonalcoholic steatohepatitis (NASH) by metabolomics using an animal model
Pharmacodynamic Analysis of the Effect of GA on Mice With Diabetes Induced by highfat diet (HFD) and STZ
Summary
Diabetes is a multi-etiological chronic metabolic disorder that is primarily characterized by pathological and physiological changes induced by insulin resistance and impaired insulin secretion. Because of changes in lifestyle and improved living standards, the global incidence of diabetes has gradually increased from 153 million in 1980 to 347 million people in 2010 (Danaei et al, 2011). The mortality rate associated with vascular complications induced by diabetes, including diabetic nephropathy, has gradually increased. Among various types of naturally occurring polyphenols, GA is one of the simplest and exists in free forms, such as tannins, ellagitannin, theaflavin-3-gallate, and epigallocatechin gallate. Previous research pointed out that free-form GA exists in tea (Kongpichitchoke et al, 2016). It is worth noting that GA occurs in tea in free and esterified forms (Matthew et al, 1997). Esterified forms include gallocatechin gallate (GCG), catechin gallate (CG), epicatechin gallate (ECG), epigallocatechin gallate (EGCG) (Quan et al, 2011)
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