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

Steve Harakeh; Mohammed Almuhayawi; Soad Al Jaouni; Saad Almasaudi; Saber Hassan; Turki Al Amri; Najiah Azhar; Elham Abd-Allah; Soad Ali; Nagla El-Shitany; Shaker A Mousa

doi:10.1016/j.sjbs.2020.09.060

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

Saudi J Biol Sci. 2020 Dec;27(12):3474-3480. doi: 10.1016/j.sjbs.2020.09.060. Epub 2020 Oct 9.

Authors

Steve Harakeh^{1

2}, Mohammed Almuhayawi³, Soad Al Jaouni^{2

4}, Saad Almasaudi⁵, Saber Hassan⁶, Turki Al Amri⁷, Najiah Azhar⁸, Elham Abd-Allah⁹, Soad Ali¹⁰, Nagla El-Shitany^{11

12}, Shaker A Mousa^{2

13

14}

Affiliations

¹ Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University (KAU), Saudi Arabia.
² Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, KAU, Saudi Arabia.
³ Department of Medical Microbiology/Parasitology and Molecular Microbiology Laboratory, King Abdulaziz University Hospital (KAUH), KAU, Saudi Arabia.
⁴ Department of Hematology/Pediatric Oncology, KAUH, Faculty of Medicine (FM), KAU, Saudi Arabia.
⁵ Biology Department, Faculty of Science, KAU, Jeddah, Saudi Arabia.
⁶ Zoology Department, Faculty of Science, Assiut Universy, Assiut, Egypt.
⁷ Family and Community Medicine Department, Faculty of Medicine in Rabigh, KAU, Jeddah, Saudi Arabia.
⁸ General Surgery, King Abdulaziz Hospital, General Directorate of Health Affairs, Makkah Region, Saudi Arabia.
⁹ Zoology Department, Faculty of Science, New Valley University, El-Kharga, Egypt.
¹⁰ Anatomy Department, FM, KAU, Jeddah, Saudi Arabia.
¹¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, KAU, Jeddah, Saudi Arabia.
¹² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
¹³ Albany Nutraceuticals, Rensselaer, NY 12144, USA.
¹⁴ Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.

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.

Keywords: Beta islet; Bodyweight; Caspase 3; Ellagic acid; Glucose; Insulin; Lipids; Metformin; Nanoformulations.