Evaluation of Antidiabetic Properties of Aqueous Stem Bark Extract of Lophira lanceolata in High Sucrose Diet-induced Type 2-Like Diabetes, Using Drosophila melanogaster Model

Abstract

Background: Diabetes mellitus is a lingering and persistent metabolic disease categorized by an inadequate insulin secretion or action. The rise in type 2 diabetes mellitus (T2DM) globally has increased the quest for an alternative therapeutic candidate. Drosophila melanogaster (fruit fly) is a model used studying diseases because of its genetic similarity to humans. Aims: this study used a Drosophila melanogaster model to evaluate the antidiabetic effect of aqueous stem bark extract of Lophira lanceolata (ASBELL) in high-sucrose diet-induced type 2-like diabetes. Methodology: For this study, flies between one and three days after emergence were used. They were divided into groups: Normal control (on drosophila standard diet), Diabetic control (30% high-sucrose diet for 7 days), Metformin-treated group received (4 mg/10 g diet) of metformin, and the treatment groups received 250, 500 or 1000 µg/10 g diet each. Fly haemolymph glucose was quantified using the glucose oxidase method to confirm induction of hyperglycaemia. trehalose, glycogen Triglyceride, and oxidative stress marker (MDA), as well as antioxidant catalase activity, were also determined. qRT-PCR was used to analyzed the gene expression of AMPK and associated key metabolic genes such as insulin receptor substrate (IRS), Acetyl-CoA carboxylase (ACC) and phosphoenolpyruvate carboxykinase (PEPCK) gene Results: after the induction, the HSD fed flies displayed some characteristics of type 2-like diabetes, when compared to the normal control group, including hyperglycemia, elevated trehalose, glycogen triglycerides and MDA with reduced catalase activity when compared to normal control. the treatment groups showed a significant decrease in glucose, trehalose, glycogen triglyceride and MDA levels, as well as an increase in catalase activity, when compared to the diabetic control group.  Gene-expression analysis shows upregulation of AMPK and IRS and downregulation of ACC and PEPCK, indicating potential improvements in insulin sensitivity, increased glucose uptake and improved lipid metabolism. Conclusion: This study, revealed that ASBELL influenced metabolic, oxidative stress and gene expression changes in high-sucrose diet-induced type 2-like diabetes in Drosophila melanogaster. The ability of ASBELL to alter biochemical parameters and modulate related gene expression suggest the possible involvement of aqueous stem bark of Lophira lanceolata as a source of bioactive compound for further investigation in metabolic disorder.