A flavonoid-rich fraction of Euphorbia peplus attenuates hyperglycemia, insulin resistance, and oxidative stress in a type 2 diabetes rat model

Abstract

<b>Background:</b> Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR) and hyperglycemia. Plants are valuable sources of therapeutic agents for the management of T2D. <i>Euphorbia peplus</i> has been widely used as a traditional medicine for the treatment of various diseases, but its beneficial role in T2D has not been fully explored. <b>Methods:</b> The anti-diabetic efficacy of <i>E. peplus</i> extract (EPE) was studied using rats with T2D induced by high-fat diet (HFD) and streptozotocin (STZ). The diabetic rats received 100, 200, and 400 mg/kg EPE for 4 weeks. <b>Results:</b> Phytochemical fractionation of the aerial parts of <i>E. peplus</i> led to the isolation of seven known flavonoids. Rats with T2D exhibited IR, impaired glucose tolerance, decreased liver hexokinase and glycogen, and upregulated glycogen phosphorylase, glucose-6-phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase). Treatment with 100, 200, and 400 mg/kg EPE for 4 weeks ameliorated hyperglycemia, IR, liver glycogen, and the activities of carbohydrate-metabolizing enzymes. EPE attenuated dyslipidemia, serum transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and liver lipid accumulation, nuclear factor (NF)-κB p65, and lipid peroxidation, nitric oxide and enhanced antioxidants. All EPE doses upregulated serum adiponectin and liver peroxisome proliferator-activated receptor γ (PPARγ) in HFD/STZ-induced rats. The isolated flavonoids showed <i>in silico</i> binding affinity toward hexokinase, NF-κB, and PPARγ. <b>Conclusion:</b> <i>E. peplus</i> is rich in flavonoids, and its extract ameliorated IR, hyperglycemia, dyslipidemia, inflammation and redox imbalance, and upregulated adiponectin and PPARγ in rats with T2D.