AUTHOR=Ayuob Nasra , Al-Shathly Mona Ramadan , Bakhshwin Abdulaziz , Al-Abbas Nouf Saeed , Shaer Nehad A , Al Jaouni Soad , Hamed Walaa H. E. 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.664248

DOI=10.3389/fphar.2021.664248

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objectives:</bold> This study was designed to assess the antidiabetic effect of combined administration of ginger (<italic>Zingiber officinale</italic> Roscoe) and cinnamon (<italic>Cinnamomum cassia</italic> L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect.</p><p><bold>Materials and methods:</bold> 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.</p><p><bold>Results:</bold> BGL significantly decreased (<italic>p</italic> = 0.01), while serum insulin and TAC significantly increased (<italic>p</italic> &lt; 0.001) in both metformin- and ginger plus cinnamon–treated groups compared to the untreated diabetic group. HOMA–β cell index significantly increased (<italic>p</italic> = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated (<italic>p</italic> &lt; 0.001), while β-catenin was insignificantly downregulated (<italic>p</italic> = 0.32) in ginger plus cinnamon–treated groups. Insulin immunoexpression in β cells significantly increased (<italic>p</italic> = 0.001, <italic>p</italic> = 0.004) in metformin- and ginger plus cinnamon–treated groups, respectively.</p><p><bold>Conclusions:</bold> 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 <italic>via</italic> upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.</p>