Effects of boschnaloside from Boschniakia rossica on dysglycemia and islet dysfunction in severely diabetic mice through modulating the action of glucagon-like peptide-1

Phytomedicine. 2019 Sep:62:152946. doi: 10.1016/j.phymed.2019.152946. Epub 2019 May 6.

Abstract

Background: Boschniakia rossica is a well-known traditional Chinese medicine for tonifying kidney and improving impotence. Boschnaloside is the major iridoid glycoside in this herb but therapeutic benefits for diabetes remained to be evaluated.

Hypothesis/purpose: The current investigation aims to study the antidiabetic effect and the underlying pharmacological mechanisms.

Study design and methods: Receptor binding, cAMP production, Ins secretion, glucagon-like peptide 1 (GLP-1) secretion, and dipeptidyl peptidase-4 activity assays were performed. Therapeutic benefits of orally administrated boschnaloside (150 and 300 mg/kg/day) were evaluated using severely 12-week old female diabetic db/db mice (Hemoglobin A1c >10%).

Results: Oral treatment of boschnaloside for 4 weeks improved diabetic symptoms including fasting blood sugar, hemoglobin A1c, glucose intolerance, and Homeostatic Model Assessment of Ins Resistance, accompanied by circulating GLP-1active and adiponectin levels. In addition, bochnaloside treatment improved islet/β cell function associated with an alteration of the pancreatic and duodenal homeobox 1 level. It was shown that boschnaloside interacted with the extracellular domain of GLP-1 receptor and enhanced glucose stimulated Ins secretion. Boschnaloside also augmented the insulinotropic effect of GLP-1. Finally, the presence of boschnaloside caused a reduction of dipeptidyl peptidase-4 activity while enhanced GLP-1 secretion from STC-1 cells.

Conclusion: It appears that bochnaloside at oral dosage greater than 150 mg/kg/day exerts antidiabetic effects in vivo through modulating the action of GLP-1.

Keywords: Bochnaloside; Dipeptidyl peptidase-4; Glucagon-like peptide-1; Iridoid glycosides; Type 2 diabetes.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucose Metabolism Disorders / drug therapy
  • Glucose Metabolism Disorders / metabolism
  • Glycated Hemoglobin / metabolism
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Iridoids / administration & dosage
  • Iridoids / pharmacology*
  • Mice
  • Orobanchaceae / chemistry
  • Plants, Medicinal / chemistry
  • Rats

Substances

  • Blood Glucose
  • Drugs, Chinese Herbal
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Iridoids
  • boschnaloside
  • Glucagon-Like Peptide 1