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

Abstract

Diabetes is the most common endocrine disorder contributing to high morbidity and mortality globally. Due to the side effects reported for anti-diabetic drugs, there is a rising interest in herbal medicine for diabetes mitigation. However, rare studies were performed to analyze the molecular effects of natural agents on diabetes. Therefore, this study is the first to assess the possible ameliorating effects of avocado and cinnamon extracts on streptozotocin (STZ)-induced disturbances in the gene expression of PDX1 and Ins1 in type-2 diabetic rats, in comparison to metformin. A total number of 50 male Albino rats were randomly divided into five groups; normal control, STZ-induced diabetic group (65mg/kg b.w divided into three doses 5days apart), three other STZ-diabetic groups were treated orally for 6weeks with metformin (500mg/kg b.w/day), an avocado fruit ethanolic extract (300mg/kg b.w/day), or a cinnamon aqueous extract (200mg/kg b.w/day). All rats were fasted overnight then euthanized, blood was collected, and serum was separated for biochemical analyses. The pancreas was processed for the evaluation of PDX1 and Ins1 gene expression by qRT-PCR. Oral administration of the avocado/cinnamon extract significantly improved the altered levels of blood glucose, insulin, lipid profile, and total antioxidant capacity (TAC) and upregulated the pancreatic expression of PDX1 and Ins1 genes. In conclusion, this study added another mechanism of anti-diabetic action for the plant extracts via upregulating the gene expression of PDX1 and Ins1 in STZ-diabetic rats. Metformin has a more profound effect than the plant extracts; however, cinnamon has a comparable effect. PRACTICAL APPLICATIONS: Diabetes is a worldwide chronic serious problem; therefore, different efficacious drug treatments are currently available. However, several side effects of these drugs also negatively affect patient welfare. Therefore, the present study provides an additive/adjunct biochemical rationale for further natural intervention strategy for type-2 diabetes through the introduction of plant-derived products that revealed a wide range of therapeutic effects without causing untoward actions. This study revealed that cinnamon and avocado extracts exhibited marked anti-diabetic and antioxidant effects in rats, as compared to the standard drug, metformin. These results augmented the previous ones and added a new molecular mechanism of action through upregulation of Ins1 and PDX1 in type-2 diabetic rats.