p53 Rather Than β-Catenin Mediated the Combined Hypoglycemic Effect of Cinnamomum cassia (L.) and Zingiber officinale Roscoe in the Streptozotocin-Induced Diabetic Model

Abstract

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now.Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger (Zingiber officinale Roscoe) and cinnamon (Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect.Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague–Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA–β cells were performed. Pancreatic gene expression of β-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques.Results: BGL significantly decreased (p = 0.01), while serum insulin and TAC significantly increased (p < 0.001) in both metformin- and ginger plus cinnamon–treated groups compared to the untreated diabetic group. HOMA–β cell index significantly increased (p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated (p < 0.001), while β-catenin was insignificantly downregulated (p = 0.32) in ginger plus cinnamon–treated groups. Insulin immunoexpression in β cells significantly increased (p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon–treated groups, respectively.Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.

Mitigation of streptozotocin‐induced alterations by natural agents via upregulation of PDX1 and Ins1 genes in male rats

“…In the present study, cinnamon administration significantly increased serum TAC in comparison to the diabetic group. Our results are in parallel with Ayuob et al (2021). This effect in part could be the result of increased activities of antioxidant enzymes (Alsoodeeri et al, 2020) as well as improved serum glutathione level (Nikzamir et al, 2014).…”

Synergistic Anti-inflammatory and Neuroprotective Effects of Cinnamomum cassia and Zingiber officinale Alleviate Diabetes-Induced Hippocampal Changes in Male Albino Rats: Structural and Molecular Evidence

“…On the other hand, administration of ginger alone or with cinnamon could significantly increase β-cell function as evidenced by increased serum insulin and HOMA-β. This is in line with some previous studies ( Al-Qulaly et al, 2021 ; Ayuob et al, 2021 ). They added that ginger and cinnamon, administrated together, increase insulin secretion and increase tissue sensitivity to insulin.…”

Protective Effects of Ginger Ethanolic Extract, Chitosan Nanoparticles, and Ginger Ethanolic Extract-Loaded Chitosan Nanoparticles on Pancreatic DNA Damage and Histological Changes in Dogs with Alloxan-Nicotinamide Induced Type 2 Diabetes

“…GEE treatment led to morphological normalization of the exocrine tissue and a partial restoration of the endocrine portion, as evidenced by the increased presence of Langerhans cells. These findings align with previous research highlighting the anti-inflammatory and antioxidant properties of ginger (Ayuob et al, 2021).…”