In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves

Molecules. 2020 Nov 1;25(21):5073. doi: 10.3390/molecules25215073.

Abstract

Background: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr (Oleaster) is a wild endemic olive tree indigenous to the Mediterranean region. Olea europea leaves represent a natural reservoir of bioactive molecules that can be used for therapeutic purposes.

Aim of the study: This work was conducted to study antidiabetic and antihyperglycemic activities of flavonoids from oleaster leaves using alloxan-induced diabetic mice. The mode of action of flavonoids against eight receptors that have a high impact on diabetes management and complication was also investigated using molecular docking.

Results: During 28 days of mice treatment with doses 25 and 50 mg/kg b.w, the studied flavonoids managed a severe diabetic state (<450 mg/dL), exhibiting a spectacular antidiabetic and antihyperglycemic activity, and improved mice health status compared to diabetic control. The in-silico mode of action of oleaster flavonoids revealed the inhibition of protein tyrosine phosphatase 1B (PTP1B), Dipeptidyl-peptidase 4 (DPP4), α-Amylase (AAM), α-Glucosidase inhibition, Aldose reductase (AldR), Glycogen phosphorylase (GP), and the activation of free fatty acid receptor 1 (FFAR1).

Conclusion: The findings obtained in the present work indicate that the flavonoids from the oleaster may constitute a safe multi-target remedy to treat diabetes.

Keywords: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr; diabetes; flavonoids; molecular docking; oleaster.

MeSH terms

  • Animals
  • Computer Simulation
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / pathology
  • Flavonoids* / chemistry
  • Flavonoids* / pharmacology
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / pharmacology
  • Mice
  • Models, Biological*
  • Olea / chemistry*
  • Plant Leaves / chemistry*

Substances

  • Flavonoids
  • Hypoglycemic Agents