In this study, we focus on resveratrol, a polyphenolic compound found in some plants such as grapes (specifically, red grape skins) and peanuts. There are many different natural ingredients that have antioxidant properties. Antioxidants have been extensively studied by neutralizing reactive oxygen/nitrogen species. One of the effective strategies for the consequences of oxidative stress and diabetes-related hyperglycemia is the use of antioxidants, especially natural antioxidants 10. Therefore, reducing oxidative stress is a crucial aspect of managing vascular diseases. The formation of free radicals is intensified by a decrease in antioxidant levels 7 and results in oxidative damage, which ultimately leads to the dysfunction of endothelial cells 8, 9. Hyperglycemia can destroy antioxidant protective enzymes, leading to an accumulation of ROS and subsequent cell damage 6.Ĭhronic hyperglycemia has progressive detrimental effects on HUVECs, manifested by increased oxidative stress. Most of these are inherent with physiological and biochemical processes that involve defects in glucose metabolism, usually due to hyperglycemia 5. However, the accumulation of ROS until oxidative stress occurs is actually the result of a variety of factors. ROS formation is associated with oxygen consumption and the action of oxidases during mitochondrial respiration. As a result, an imbalance between enzymatic and non-enzymatic antioxidants and ROS generation leads to endothelial dysfunction, endothelial cell necrosis and apoptosis due to increased endothelial permeability 4. In response to a hyperglycemic environment, several proinflammatory pathways also participate in oxidative and antioxidant processes. Increased ROS production causes aberrant regulation of many genes, including inflammatory cytokines and adhesion molecules. Reactive oxygen species (ROS) are intermediate molecules that act as secondary messengers in the cell 3. Studies have proven that oxidative stress mediates the production and secretion of cytokines in inflammation and endothelial dysfunction. Since an endothelial function can be a marker for the progression of these diseases, a more serious approach is needed to treat abnormal endothelial function 2. The natural vascular endothelium is considered a protector of cardiovascular health 1, while its abnormality is a major cause of many disorders including peripheral vascular disease, heart disease, diabetes, insulin resistance and chronic heart failure. RGNps have demonstrated significant potential in alleviating oxidative stress and preventing endothelial cell disorders.Įndothelial cells are important components of blood vessels, playing an important role in cardiovascular homeostasis by regulating blood flow and fibrinolysis, angiogenesis, monocyte adhesion, and platelet aggregation. The MFC provides a distinct advantage in observing cell morphology and inducing endothelial cell dysfunction. Morphologically, cells in the MFC presented superior structure compared to those in traditional cell culture plates, and the induction of hyperglycemia successfully led to the formation of multinucleated variant endothelial cells (MVECs). In the MFC,the DCFH-DA analysis indicated that RGNPs (20 nm) reduced cellular oxidative stress by 57–82%, surpassing both CGNps and free Resveratrol. Notably, RGNPs (20 nm) exhibited antioxidative properties through DPPH scavenging activity (%) in the range of approximately 38–86% which was greater than that of CGNps at about 21–32%. RGNPs, both 3.0 ± 0.5 nm and 20.2 ± 4.7 nm, consistently showed high cell viability (more than about 90%) across tested concentrations. Free Resveratrol demonstrated peak DPPH scavenging activity but had a cell viability of about 24–35%. For assessing intracellular oxidative stress, the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) assay was conducted, and results from both the cell culture plate and MFC were compared. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay was employed to measure the extracellular antioxidant potential, and cell viability was determined using the Alamar Blue test. A microfluidic chip (MFC) with dynamic flow conditions was designed to simulate body vessels and to investigate the antioxidant properties of resveratrol gold nanoparticles (RGNps), citrate gold nanoparticles (CGNps), and free Resveratrol on human umbilical vein endothelial cells (HUVEC). Addressing the challenges of its limited solubility and stability, gold nanoparticles (GNps) were utilized as carriers. Resveratrol, a plant polyphenol, possesses antioxidant properties that can mitigate oxidative stress. Vascular endothelial cells play a vital role in the health and maintenance of vascular homeostasis, but hyperglycemia disrupts their function by increasing cellular oxidative stress.
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