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

• Published in: Toxicology and applied pharmacology Vol. 365; pp. 30 - 40
• Main Authors: Eitah, Hebatollah E., Maklad, Yousreya A., Abdelkader, Noha F., Gamal el Din, Amina A., Badawi, Manal A., Kenawy, Sanaa A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-02-2019
• Subjects: Adiponectin; Diabetes mellitus; Oxidative stress; Pancreatic islets; Quercetin; Sitagliptin; Oxidative stress; Sitagliptin; Pancreatic islets; Diabetes mellitus; Quercetin; Adiponectin
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2018.12.011

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.
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.
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.
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.
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.
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•Quercetin/sitagliptin combination normalized serum glucose and C-peptide levels.•This combination ameliorated hyperlipidemia, oxidative and inflammatory burden.•It restored pancreatic islets' as well as β-cells' integrity and function.•These findings suggest this combination as an efficient approach in combating T2DM.