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

Reem S Alruhaimi; Gomaa Mostafa-Hedeab; Maisa Siddiq Abduh; Albandari Bin-Ammar; Emad H M Hassanein; Emadeldin M Kamel; Ayman M Mahmoud

doi:10.3389/fphar.2023.1204641

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

Front Pharmacol. 2023 Jun 16:14:1204641. doi: 10.3389/fphar.2023.1204641. eCollection 2023.

Authors

Reem S Alruhaimi¹, Gomaa Mostafa-Hedeab^{2

3}, Maisa Siddiq Abduh^{4

5}, Albandari Bin-Ammar⁶, Emad H M Hassanein⁷, Emadeldin M Kamel⁸, Ayman M Mahmoud^{9

10}

Affiliations

¹ Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
² Pharmacology Department, Medical College, Jouf University, Sakaka, Saudi Arabia.
³ Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
⁴ Immune Responses in Different Diseases Research Group, Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia.
⁷ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
⁸ Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
⁹ Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, United Kingdom.
¹⁰ Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

Abstract

Background: 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. Euphorbia peplus 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. Methods: The anti-diabetic efficacy of E. peplus 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. Results: Phytochemical fractionation of the aerial parts of E. peplus 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 in silico binding affinity toward hexokinase, NF-κB, and PPARγ. Conclusion: E. peplus is rich in flavonoids, and its extract ameliorated IR, hyperglycemia, dyslipidemia, inflammation and redox imbalance, and upregulated adiponectin and PPARγ in rats with T2D.

Keywords: Euphorbia; diabetes; inflammation; insulin resistance; oxidative stress.

Grants and funding

This research was funded by the Nourah Bint Abdulrahman University Researchers Supporting Project (grant number PNURSP 2023R381), Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.