A novel layered double hydroxide-hesperidin nanoparticles exert antidiabetic, antioxidant and anti-inflammatory effects in rats with diabetes

Mol Biol Rep. 2021 Jun;48(6):5217-5232. doi: 10.1007/s11033-021-06527-2. Epub 2021 Jul 10.

Abstract

Background: Incidence of diabetes has increased significantly worldwide over recent decades. Our objective was to prepare and characterize a novel nano-carrier of hesperidin to achieve a sustained release of hesperidin and to explore the potency of the novel formula as an antidiabetic agent compared to metformin in type 2 diabetic rats.

Methods: Hesperidin was loaded on MgAl-layered double hydroxide (LDH). The formula was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy, and dynamic light scattering. The release profile of hesperidin and MgAl-LDH-Hesperidin were studied in vitro. The parameters studied in vivo were blood glucose, glycated hemoglobin (HbA1c), insulin, lipid profile, and liver glycogen levels. We also investigated the levels of interleukin (IL)-17, tumor necrosis factor-Alfa (TNF-α), malondialdehyde (MDA), catalase, and the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and nuclear factor erythroid 2-related factor-2 (NrF2).

Results: There were variations in the XRD patterns and FTIR confirming the physical adsorption of hesperidin on the surface of LDH. The results indicated that the diabetic rats treated with administration of antidiabetic formula, MgAl-LDH-Hesperidin, showed a beneficial effect on the levels of blood glucose, insulin, HbA1c%, and lipid profile, comparing to diabetic control rats. The antidiabetic agent also showed a significant decrease in the levels of TNF-α, IL-17, and MDA, and an increase in the level of catalase. Marked upregulation of the expression levels of mRNA for PPARγ and NrF2 were recorded.

Conclusion: The novel nano-hesperidin formula MgAl-LDH-Hesperidin revealed a sustained release of hesperidin and exhibited antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory properties, and also is a promising agent for effective delivery of drugs to treat type 2 diabetes.

Keywords: Hesperidin; Layered double hydroxide; Lipid profile; Oxidative stress; Type 2 diabetes.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / metabolism
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Glucose / metabolism
  • Hesperidin / pharmacology*
  • Hydroxides / pharmacology*
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Male
  • Malondialdehyde
  • Nanoparticles / chemistry
  • Oxidative Stress / drug effects
  • PPAR gamma / metabolism
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Blood Glucose
  • Hydroxides
  • Hypoglycemic Agents
  • Insulin
  • PPAR gamma
  • Malondialdehyde
  • hydroxide ion
  • Hesperidin
  • Glucose