Molecular mechanisms of anti-diabetes effects of Mormodica charantia L. Ethanolic leaf extract on type 2 diabetes in strains of Drosophila melanogaster meigen, 1838

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by reduced insulin sensitivity and poor glucose utilization. This study examined the anti-diabetic potential and molecular mechanisms of Mormodica charantia (MC) ethanolic leaf extract in strains of Drosophila melanogaster . T2D was induced using a high sucrose diet (2.5 g/10 g), followed by co-administration of M. charantia (MC) extract (100 mg, 150 mg, and 200 mg) and 16 mg of metformin for ten days. MC at 200 mg significantly improved eclosion rates and starvation resistance in the Harwich strain, while 150 mg showed the strongest hypoglycemic effect in the indigenous NgD3 strain. The extract alleviated heat stress and reversed sucrose-induced Malpighian tubule dysfunction, (p<0.001), which elevated creatinine (1.92 mg/dl and 1.59 mg/dl) both sexes and sodium levels (1.67 mg/dl), particularly in male flies. At 150 mg, effectively reduced creatinine and urea levels (1.68 µ/l). The 100 mg increased ALP levels (9.09 µ/l). At 200mg, M. charantia, significantly upregulated CG4607 expression (0.5656) in Harwich strain, while causing a significant downregulation (-5.79586) in NgD3 strain. Squalene demonstrated the highest binding affinity (-7.5 kcal/mol). Single Nucleotide Polymorphism analysis revealed strain-specific genetic responses, and phylogenetic analysis showed three distinct clusters. These findings suggest MC extract modulates physiological and molecular responses in insulin-resistant Drosophila, highlighting its potential as a plant-based anti-diabetic therapy.