Abstract
Diabetes mellitus (DM) is a severe chronic metabolic disease with increased mortality and morbidity. The pathological progression of DM is intimately connected with the formation and activation of oxidative stress (OS). Especially, the involvement of OS with hyperglycemia, insulin resistance, and inflammation has shown a vital role in the pathophysiological development of DM and related complications. Interestingly, accumulating studies have focused on the exploration of natural antioxidants for their improvement on DM. Of specific interest is gallic acid (GA), which is rich in many edible and herbal plants and has progressively demonstrated robust antioxidative and anti-inflammatory effects on metabolic disorders. To provide a better understanding of its potential therapeutic impacts and enhancement of human health care, the available research evidence supporting the effective antidiabetic properties of GA and relevant derivatives are needed to be summarized and discussed, with emphasis on its regulation on OS and inflammation against DM. This review aims to highlight the latest viewpoints and current research information on the role of OS in diabetes and to provide scientific support for GA as a potential antihypoglycemic agent for DM and its complications.
Highlights
Homeostatic disruption in host metabolism and the resultant hyperglycemia or insulin resistance act as the leading cause for diabetes mellitus (DM) development
The pathophysiological progression of diabetes and associated complications have been found to be associated with different complex mechanisms, and hyperglycemia, insulin resistance, inflammation, and oxidative stress (OS) are commonly considered as the major causal factors implicated in the worsening of diabetes-associated perturbations
Other interesting questions raised in this review highlight the fact that the in vitro multitarget properties of Gallic acid (GA) often do not coincide with in vivo results, probably due to poor oral bioavailability, indicating the demand to investigate its structure modification with the aim to improve its absorption and the distribution in mammals, which thereby enhances its healthy properties and efficacy when applying new formulation
Summary
Homeostatic disruption in host metabolism and the resultant hyperglycemia or insulin resistance act as the leading cause for diabetes mellitus (DM) development. The antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) can catalyze the degradation of ROS, while the nonenzymatic antioxidants including glutathione (GSH), polyamine, and bilirubin can directly trap and scavenge free radicals, both resulting in the elimination and reduction of cellular impairments External antioxidants, such as vitamin C, vitamin E, carotenoids, and various phenylpropanoid derivatives (phenolics, flavonoids, tannins, lignans, and lignins), have been reported with the potential of enhancing the antioxidant defense systems. The hyperglycemia-related source of ROS contains the autoxidation of lipid or glucose and the reduced activity of antioxidants enzymes including SOD, GPX, and CAT, all of which are involved in the antioxidant defense of tissues in diabetic conditions. The vast array of molecular mechanisms accounting for hyperglycemia-induced excessive ROS production have been well documented, and some important metabolic pathways are regarded as major contributors to the homeostasis of cellular redox, which is potentially associated with further activation of redox-sensitive genes [1], the following of which are emphasized: (1) Depletion of NADPH via the elevated glucose-induced polyol pathway results in less GSH generation from glutathione disulfide, subsequently contributing to ROS production and OS; (2) hyperglycemia-mediated protein kinase C (PKC) elevates the content of diacylglycerol and increased NADPH oxidases (NOX) activity; (3) the upregulated interaction between advanced glycation end products (AGEs) and RAGEs promotes ROS formation through NADPH oxidase and mitochondrial field [2]; (4) the hexosamine biosynthetic activation promotes the increased generation of uridine diphosphate (UDP)N-acetylglucosamine (GlcNAc) that could induce the elevation of protein glycosylation in the pathological progression of diabetic complications
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