Efficacy of red algae and artichoke extracts in disrupting antioxidant/PI3K/RBP-4 pathway in high-fat diet-induced metabolic disorders in rats

Abstract

Abstract Background Insulin resistance (IR) leads to various metabolic abnormalities, including diabetes mellitus, obesity, nonalcoholic steatohepatitis, and neurodegenerative disorders. Natural products rich in nontoxic phytochemicals are cost-effective and widely used to manage insulin resistance, reducing drug interactions. Artichoke stems and red algae contain several phytochemical compounds that exert antioxidant and anti-inflammatory effects. Aim This study aims to explore and compare the preventive and therapeutic effects of red algae and artichoke stem extracts against high-fat diet-induced insulin resistance and then compare their impacts with those of the reference drug metformin, which is commonly used for treating type 2 diabetes. Methods The animals were fed a high-fat diet for eight weeks to induce insulin resistance. The plants were then treated orally with 100 mg/kg body weight red algae, artichoke extracts, or metformin per day for 14 days. The protective rat groups received the extracts at the same dose for 14 days before being fed the high-fat diet for eight weeks. Commercial kits and standardized methods were used to measure blood diabetic profiles (glucose, insulin, lipid profile, fructosamine, and retinol-binding protein-4 (RBP-4)) and liver oxidative stress parameters, nuclear factor-κβ (NF-κβ), peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), retinol-binding protein-4 (RBP-4), and phosphatase and tensin homolog (PTEN). Results Our results showed that both extracts inhibited NF-κB and PTEN while enhancing PI3K, RPB-4, and PPAR-γ due to their potent antioxidant properties. They also increased insulin sensitivity, as reflected by reduced blood glucose and lipid profile levels and normalized fructosamine and RBP-4. Additionally, these extracts prevent oxidative stress-induced hepatic and nephric cell dysfunction, as confirmed by improved blood, liver, and kidney parameters. Conclusion Therefore, both extracts could be good antioxidant treatments for oxidative stress-related insulin resistance because they restore the balance of the PI3K/PPAR-γ/RBP-4 pathway. This pathway increases glucose uptake, stops gluconeogenesis, speeds up lipid metabolism, and stops the inflammation pathway.

Keywords

• Insulin resistance
• Oxidative stress
• Metformin
• NF-κβ
• PPAR-γ
• PTEN