Antidiabetic effects of novel ellagic acid nanoformulation: Insulin-secreting and anti-apoptosis effects

Abstract

Antioxidants are one of the effective treatment lines in managing type 2 diabetes (typ2diab) and its complications. Nanoformulations could help in ameliorating the oral bioavailability and biocompatibility properties. Ellagic acid (Ella) is a natural antioxidant compound commonly present in fruits. This study examined the effect Ella nanoparticles (Ella NPs) alone and combined with metformin, the standard antidiabetic drug, on controlling blood glucose in typ2diab. Forty-eight adult Sprague-Dawley rats were used in this study. Except for the control group that was fed a regular pellet diet, all animals were fed a high-fat diet (HFD) for 9 weeks. For the last 4 weeks, rats were injected with streptozotocin (35 mg/kg). Then the rats were randomized into 8 groups: control, HFD, diabetic, Ella, Ella + metformin, Ella NPs, and Ella NPs + metformin. Data showed that Ella NPs improved blood glucose levels and the body weights of diabetic rats throughout all the weeks of the experiment whereas effects of the regular Ella were limited to the last two weeks of the treatment. Additionally, data demonstrated that the antidiabetic action of Ella NPs and its effective duration were similar to metformin. Ella NPs led to a lowering effect on lipid profile markers (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL)), superior to the regular Ella, which reduced only TG and VLDL. Results of the pathological examination showed improved number and activity of beta islets in all treatment groups. The most enhanced islets were in the Ella NPs and metformin group. The different treatments decreased caspase 3 and increased insulin gene expression, and the effect was superior in the Ella NPs and metformin group. The results of this study confirmed that Ella could manage typ2diab by lowering glucose and lipid levels and improving body weight with the superiority of Ella NPs. The mechanisms behind these effects are inhibition of beta-cell apoptosis and stimulation of insulin production.

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential

“…In a recent study, free EA and EA nanoparticles were administrated to diabetic rats fed a high-fat diet. The results demonstrated that EA nanoparticles improved glucose levels and body weight for longer periods compared to regular EA [269]. Moreover, better results for EA nanoparticles were also observed on lipid profile markers, such as total cholesterol, triglycerides, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL), and insulin production levels.…”

Preventive Effect of Ellagic Acid on Cardiac Dysfunction in Diabetic Mice through Regulating DNA Hydroxymethylation

“…Previous research observed that the given 250 and 500 mg/kg of pomegranate extract significantly reduced serum TC, TG, HDL-C, and LDL-C levels in a hyperglycemic state . However, there were no changes in serum TC, HDL-C, and LDL-C after intraperitoneal injection of 10 mg/kg of EA …”

“…46 However, there were no changes in serum TC, HDL-C, and LDL-C after intraperitoneal injection of 10 mg/kg of EA. 47 Recent studies revealed the critical role of DNA 5hmC in heart development and pathophysiology; 11,48,49 therefore, we focused our attention on the levels of DNA 5hmC in diabetic mice hearts. A previous study showed that DNA 5hmC levels were lower in cardiac tissues of HFD-fed mice, and the association between DNA 5hmC levels and cardiac function was found by measuring heart remodeling markers.…”

Ellagic acid regulates hyperglycemic state through modulation of pancreatic IL-6 and TNF- α immunoexpression

“…A phenolic substance, EA is found in various fruits, e.g., raspberries, strawberries, blueberries and walnuts. The compound has been shown to have anti-diabetic activity ( Harakeh et al, 2020 ). In this study, EA was derived from strawberry fruit and analyzed using FT-IR spectroscopy.…”