The effectiveness comparisons of eugenosedin-A, glibenclamide and pioglitazone on diabetes mellitus induced by STZ/NA and high-fat diet in SHR

J Pharm Pharmacol. 2021 Apr 27;73(6):835-845. doi: 10.1093/jpp/rgab029.

Abstract

Objectives: Eugenosedin-A (Eu-A), an adrenergic and serotonergic antagonist, is known to have anti-metabolic syndrome effects. In this study, we evaluated its protective effects against diabetes mellitus (DM) in spontaneous hypertensive rats (SHR) and compared it with two anti-diabetes medications, glibenclamide (Gli) and pioglitazone (Pio).

Methods: We divided 10-week-old SHRs into five groups: a control group fed a normal diet; an untreated DM group induced by injecting the SHRs with STZ/NA and feeding them a high-fat diet (HFD); and three treated groups (after giving STZ/NA and HFD) gavage given with Eu-A, Gli or Pio (5 mg/kg per day) for 4 weeks.

Key findings: The untreated DM group weighed less and had hyperglycaemia, hypoinsulinemia and hyperlipidemia. They were also found to have aberrant glucose-dependent insulin pathways, glucose metabolism and lipid synthesis proteins, while the controls did not. Eu-A, Gli and Pio ameliorated the above biochemical parameters in the treatment groups. Eu-A and Pio, but not Gli, improved hypertension and tachycardia.

Conclusions: Taken together, Eu-A ameliorated DM, hypertension and tachycardia by improving glucose, lipid homeostasis and anti-adrenergic, serotonergic activities. We concluded that Eu-A could be used in the development of an effective agent for controlling DM and its complications.

Keywords: SHR; diabetes mellitus; eugenosedin-A; glibenclamide; pioglitazone.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diet, High-Fat
  • Glyburide / pharmacology
  • Hypertension / drug therapy
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Male
  • Pioglitazone / pharmacology
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Sprague-Dawley
  • Streptozocin

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Piperazines
  • eugenosedin-A
  • Streptozocin
  • Glyburide
  • Pioglitazone