Brahmi Ghrita exerts nephroprotective effect on polycystic phenotype in the Malpighian tubules of caspase 3 deletion mutants of Drosophila melanogaster
摘要
Polycystic kidney disease (PKD) is a genetic disorder characterized by progressive cyst formation, epithelial disorganization, and impaired fluid transport, ultimately leading to renal failure. Disruption of cytoskeletal dynamics and epithelial polarity is central to PKD pathogenesis. The Drosophila Malpighian tubules (MTs) are human kidney analogs, and caspase-3/Drice deletion mutants exhibit phenotype similar to polycystic kidneys. This study evaluates the potential of the Ayurvedic formulation, Brahmi Ghrita (BG), in ameliorating cystic defects observed in the Drice deletion mutant MTs. BG supplementation effectively restored the normal phenotype of the tubules with a significant reduction in cyst numbers, demonstrating a nephroprotective effect in Drosophila MTs. This resulted in improved viability as evidenced by enhanced pupation and eclosion rates in Drice mutants upon BG supplementation. Restoration of Rho1 and Gelsolin levels led to improved cytoskeletal organization and cell polarity in Drice mutants. BG supplementation increased the number of stellate cells, as well as restored their shape. BG supplementation resulted in reduced uric acid accumulation and enhanced Na+/K+-ATPase expression, thus restoring the tubular efflux activity. This protection is achieved through the coordinated restoration of cytoskeletal integrity, epithelial polarity, and ion transport mechanisms. These findings provide evidence for the role of BG in maintaining renal tubule architecture and function.