Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia and dyslipidemia caused by impaired insulin secretion and resistance of the peripheral tissues. A major pathogenesis of T2DM is obesity-associated insulin resistance. Gynura divaricata (L.) DC. (GD) is a natural plant and has been reported to have numerous health-promoting effects on both animals and humans. In this study, we aimed to elucidate the regulatory mechanism of GD improving glucose and lipid metabolism in an obesity animal model induced by high-fat and high-sugar diet in combination with low dose of streptozocin and an insulin-resistant HepG2 cell model induced by dexamethasone. The study showed that the water extract of GD (GD extract A) could significantly reduce fasting serum glucose, reverse dyslipidemia and pancreatic damage, and regulate the body weight of mice. We also found that GD extract A had low toxicity in vivo and in vitro. Furthermore, GD extract A may increase glucose consumption in insulin-resistant HepG2 cells, markedly inhibit NF-κB activation, and decrease the impairment in signaling molecules of insulin pathway, such as IRS-1, AKT, and GLUT1. Overall, the results indicate that GD extract A is a promising candidate for the prevention and treatment of T2DM.
The activation of M1-type macrophages are dominant cells secreting proinflammatory present within the inflamed synovium in the progression of osteoarthritis (OA). Increased oxidative stress, such as redundant ROS and hydrogen peroxide (H2O2), are important factors in driving macrophages to polarize into M1 type. In this study, metal-polyphenol nanoformulations (Cu-Epigallocatechin-3-gallate (Cu-EGCG) nanosheets) were synthesized through the coordination interaction between EGCG and copper ions, which possess the antioxidant effect of EGCG and anti-inflammatory of Cu2+. Results showed that Cu-EGCG nanosheets are biocompatible and the Cu2+ could be sustained released from the nanoparticles. Exhibiting multienzyme-like antioxidative activity, Cu-EGCG nanosheets could effectively scavenge the excessive intracellular ROS, leading to significantly decreased expression of the pro-inflammatory cytokines, which could reduce the expression of M1-type macrophages and exhibit excellent promotion on shifting macrophages to M2 phenotypes. Moreover, the secreted factor from the cell supernatant of Cu-EGCG treated macrophages exhibited anti-inflammatory potential in chondrocytes of inflamed synovial joints. This study suggests a novel strategy for OA therapy by using metal-polyphenol nanoformulations targeting macrophages.
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