Metformin

Diabetes is a life-threatening health condition that requires expensive treatment and places a significant financial burden on society. Consequently, this study aimed to explore the potential of low and high concentrations of ginger extract, ZnO-NPs, and a combination of both to help manage diabetes and reduce high levels of lipids in diabetic rats.

The research focused on agglomerated nanoparticles under 100 nm, specifically ZnO nanoparticles. The size of the nanoparticles was determined using X-ray diffraction analysis and scanning electron microscopy analysis, with a monodisperse particle size distribution of 20 to 48 nm and an average size of 38 nm, as shown by dynamic light scattering. Fourier transform infrared spectroscopy revealed the presence of typical peaks of ginger extract and ZnO-NPs in the nanocomposite structure. The pancreatic tissue histopathological study indicated that a concentration of 10 mg/kg of the composite had the most significant antidiabetic effect compared to other treatments. Lower concentrations could significantly reduce and balance fasting blood sugar and triglycerides levels while also increasing the high-density lipoproteins levels. However, all treatments induced a significant decrease in total cholesterol and low-density lipoproteins levels. Only metformin and ZnO-NPs in lower concentrations could decrease very low-density lipoproteins levels. The molecular technique showed that a low concentration of the composite led to the most significant decrease in Tnf-α gene expression compared to the diabetic group. The expression of the glutathione peroxidase 1 (Gpx1) gene in treated groups had no significant difference with the level of Gpx1 expression in the control rats.

In general, this study demonstrated that lower concentrations of the treatments, especially composite, were more effective for treating diabetic rats due to reduced pancreatic tissue damage.

JOURNAL/nrgr/04.03/01300535-202409000-00037/figure1/v/2024-01-30T062302Z/r/image-tiff Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models. Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis. Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis. Previous studies have shown that, when used to treat cardiovascular and digestive system diseases, metformin can also upregulate heme oxygenase-1 expression. Therefore, we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury. To test this, we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury. Next, we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis. Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury. Subsequently, we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord, and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury. Taken together, these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury, and that this effect is partially dependent on upregulation of heme oxygenase-1.