Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 2, pp 243–258 | Cite as

Cinnamaldehyde ameliorates STZ-induced rat diabetes through modulation of IRS1/PI3K/AKT2 pathway and AGEs/RAGE interaction

  • Marwa E. Abdelmageed
  • George S. Shehatou
  • Rami A. Abdelsalam
  • Ghada M. SuddekEmail author
  • Hatem A. Salem
Original Article


Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder considered to be the most predominant form of diabetes throughout the world. This study aimed to investigate the possible effects of cinnamaldehyde (CIN) on insulin signaling pathways in STZ-induced T2D rat model. T2D was originated by feeding rats with a high-fat diet (HFD) plus 25% fructose solution plus streptozotocin (STZ) (35 mg/kg, i.p.). CIN effects were investigated on fasting blood glucose, insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), liver biomarkers, lipid profile, oxidative stress biomarkers, serum advanced glycation end products (AGEs) and its receptors (RAGE) in the aorta, and histopathology of the liver and aorta. Additionally, the mRNA expression of hepatic insulin signaling pathway genes, phosphorylated AKT (serine 473) (P-AKT ser473) level, and aortic nitric oxide synthase3 (eNOS) and NADPH oxidase4 (NOX4) were determined. CIN treatment for 30 days significantly decreased OGTT, ITT, fasting blood glucose, insulin, and HOMA-IR and increased HOMA-β index when compared to diabetic rats. CIN also improved lipid profile and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, serum AGEs, and aortic RAGE. Additionally, CIN treatment significantly decreased hepatic malondialdehyde (MDA), increased hepatic and aortic glutathione (GSH) and superoxide dismutase (SOD), and decreased steatosis and inflammation observed in liver tissue of rats. Additionally, significant elevation in mRNA expression of insulin receptor substrate1 (IRS1), phosphatidylinositol 3-kinase regulatory subunit1 (PI3K-P85 subunit), and AKT serine/threonine kinase2 (AKT2); increased levels of P-AKT ser473 and aortic eNOS; and decrease in mRNA expression of NOX4 were detected in CIN-treated group when compared to diabetic group. This study suggests antidiabetic and antioxidant effects of CIN probably through upregulation of eNOS and IRS1/PI3K/AKT2 signaling pathway and alleviating AGEs, RAGE, and NOX4 elevation.


Cinnamaldehyde Type 2 diabetes Rats Streptozotocin High-fat diet Fructose Oxidative stress Advanced glycation end products Insulin signaling pathway 


Author contribution statement

MA, GS, GMS, and HS designed the research. MA and GS conducted experiments and analyzed data. MA and GMS wrote the manuscript. GS, GMS, and HS revised the manuscript. RA performed pathological assessments. All authors read and approved the manuscript.

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marwa E. Abdelmageed
    • 1
  • George S. Shehatou
    • 1
  • Rami A. Abdelsalam
    • 2
  • Ghada M. Suddek
    • 1
    Email author
  • Hatem A. Salem
    • 1
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyMansoura UniversityMansouraEgypt
  2. 2.Department of Pathology, Faculty of MedicineMansoura UniversityMansouraEgypt

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