Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats

Toxicol Appl Pharmacol. 2019 Feb 15:365:30-40. doi: 10.1016/j.taap.2018.12.011. Epub 2018 Dec 19.

Abstract

Background: Since many diabetic patients require combination therapy, the use of herbal remedies with anti-diabetic activity represents a vital option in diabetes mellitus (DM) management. It has been reported that quercetin has hypoglycemic alongside anti-inflammatory and antioxidant activities.

Aim: The present study aimed to investigate the effectiveness of combining quercetin with sitagliptin; a selective dipeptidyl peptidase-IV (DPP-IV) inhibitor, in the management of streptozotocin (STZ)-induced diabetic rats.

Methods: DM was induced by a single injection of STZ (45 mg/kg, i.p.) in male adult albino Wistar rats. Diabetic rats were orally treated with sitagliptin (70 mg/kg), quercetin (50 mg/kg) or their combination daily for three consecutive weeks. Serum levels of glucose, C-peptide, total cholesterol, triglycerides, malondialdehyde (MDA), superoxide dismutase, (SOD), reduced glutathione (GSH), tumor necrosis factor alpha, (TNF-α), nuclear factor kappa-B, (NF-κB) and adiponectin were estimated. In addition, histopathological, morphometrical and immunohistochemical examinations of pancreatic tissues were conducted.

Results: The combined administration of quercetin and sitagliptin normalized serum C-peptide, MDA, and significantly increased SOD, GSH and decreased NF-κB more than sitagliptin alone. Moreover, this combination normalized Islet number, β-cells' number, area and perimeter alongside restoring the immunostaining intensity of β-cells.

Conclusion: Our results suggest the use of quercetin/sitagliptin combination for treating DM based on the observed improvements in glycemic control, metabolic profile, oxidative and inflammatory status, islet structure as well as β-cells function compared with either treatment alone.

Keywords: Adiponectin; Diabetes mellitus; Oxidative stress; Pancreatic islets; Quercetin; Sitagliptin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Glutathione / blood
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Malondialdehyde / blood
  • NF-kappa B / blood
  • Oxidative Stress / drug effects*
  • Quercetin / pharmacology*
  • Rats, Wistar
  • Sitagliptin Phosphate / pharmacology*
  • Streptozocin*
  • Superoxide Dismutase / blood

Substances

  • Antioxidants
  • Biomarkers
  • Blood Glucose
  • C-Peptide
  • Dipeptidyl-Peptidase IV Inhibitors
  • NF-kappa B
  • Malondialdehyde
  • Streptozocin
  • Quercetin
  • Superoxide Dismutase
  • Glutathione
  • Sitagliptin Phosphate