Structural dependence of antidiabetic effect of steviol glycosides and their metabolites on streptozotocin-induced diabetic mice

J Sci Food Agric. 2020 Aug;100(10):3841-3849. doi: 10.1002/jsfa.10421. Epub 2020 May 8.

Abstract

Background: Stevia has been proposed as a potential antidiabetic sweetener, mainly based on inconsistent results from stevioside or the plant extract, yet lacking relative experimental evidence from individual steviol glycosides (SGs) and their metabolites.

Results: The results systematically revealed that the typical SGs and their final metabolite (steviol) presented an antidiabetic effect on streptozotocin (STZ) diabetic mice in all assayed antidiabetic aspects. In general, the performance strength of the samples followed the sequence steviol > steviol glucosyl ester > steviolbioside > rubusoside > stevioside > rebaudioside A, which is opposite to their sweetness strength order, and generally in accordance with the glucosyl group numbers in their molecules. This may imply that the antidiabetic effect of the SGs might be achieved through steviol, which presented antidiabetic performance similar to that of metformin with a dose of 1/20 that of metformin. Moreover, the 18 F-fluorodeoxyglucose traced micro-PET experiment revealed that stevioside and steviol could increase the uptake of glucose in the myocardium and brain of the diabetic mice within 60 min, and decrease the accumulation of glucose in the liver and kidney.

Conclusions: The SGs and steviol presented an antidiabetic effect on STZ diabetic mice in all assayed aspects, with an induction time to start the effect of the SGs. Stevioside and steviol could increase uptake of glucose in the myocardium and brain of the diabetic mice, and decrease accumulation of glucose in the liver and kidney. The performance strength of the SGs is generally in accordance with glucosyl group numbers in their molecules.

Keywords: anti-diabetic; diabetes mellitus; metformin; steviol; steviol glycoside.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diterpenes, Kaurane / administration & dosage*
  • Diterpenes, Kaurane / metabolism
  • Glucose / metabolism
  • Glucosides / administration & dosage*
  • Glucosides / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Plant Extracts / administration & dosage*
  • Plant Extracts / metabolism
  • Plant Leaves / chemistry
  • Stevia / chemistry*
  • Streptozocin

Substances

  • Diterpenes, Kaurane
  • Glucosides
  • Hypoglycemic Agents
  • Plant Extracts
  • stevioside
  • steviol
  • Streptozocin
  • Glucose