In-vivo Evaluation of Nephroprotective Activity of Naringenin against ADPKD and MDCK-derived Cysts

Abstract

Aim: Determining the in-vivo assessment of Naringenin’s nephroprotective efficacy against Autosomal dominant polycystic kidney disease (ADPKD) and Madin-Darby canine kidney (MDCK) derived cysts. Method: Our research on the molecular mechanism of naringenin, a flavonoid present in plants and berries that has been shown to limit cell growth and protect against cancer in in-vitro and animal models, was conducted using dictyostelium, a simple, controllable biomedical model. Cultured MDCK cells were used to generate differentiated tubule cells, and these findings were extrapolated to a human kidney model employing these cells. Results: While naringenin inhibited growth in dictyostelium, it had no effect on development. In a random-gene-knockout screen, a TRPP2 (polycystin-2) knockout mutant was discovered to be resistant to naringenin’s effects on growth and random-cell movement. Changes in the divalent transient receptor cause polycystic kidney disease type 2 potential cation channel TRPP2. We found that the growth of cysts and MDCK cells might be inhibited by naringenin. Partial resistance to naringenin was achieved in this model by lowering TRPP2 levels via siRNA, as evidenced by the presence of larger cysts following treatment with 3 and 10 M naringenin compared to controls. Naringenin had no effect on chloride secretion. Conclusion: Naringenin’s influence on cell proliferation is mediated by TRPP2 in both dictyostelium and mammalian kidney cells, despite their vast evolutionary distance from one another (polycystin-2). Naringenin will be the subject of more research as a possible new therapeutic treatment for ADPKD