In Vivo And In Silico Evaluation Of Fucosterol As A Potential Renin Inhibitor In Streptozotocin-Induced Diabetic Kidney Disease In Wistar Rats

The study aims to evaluate the potential of fucosterol, a phytocompound, as a renin inhibitor for the treatment of diabetic kidney disease (DKD), by comparing its molecular interactions and pharmacological characteristics with the clinically used renin inhibitor aliskiren. Methods Molecular docking studies were conducted to analyze the binding affinity of fucosterol and aliskiren with the renin enzyme. Inhibition constants (Ki) were computed to assess the inhibitory strength of both compounds. Pharmacokinetic and drug-likeness properties (e.g., molecular weight, lipophilicity, rotatable bonds, topological polar surface area) were evaluated using in silico tools. In vivo studies were performed using streptozotocin (STZ)-induced diabetic Wistar rats to assess the therapeutic effect of fucosterol on plasma renin activity, oxidative stress markers, and kidney histopathology. Results Docking analysis showed that fucosterol exhibited a stronger binding affinity with renin (-11.0 kcal/mol) than aliskiren (-9.0 kcal/mol), suggesting more stable molecular interactions. Fucosterol also demonstrated a lower inhibition constant (Ki) than aliskiren, supporting its higher inhibitory potency. Pharmacokinetic analysis indicated that fucosterol is lighter, more flexible, and more lipophilic, with a bioavailability score of 0.55, making it favorable for oral absorption. In in vivo studies, STZ-induced diabetic rats showed a significant increase in plasma renin activity (p < 0.05), which was markedly reduced upon fucosterol treatment. Fucosterol improved both enzymatic (SOD, catalase, GST, GPx) and non-enzymatic (GSH, vitamin C, vitamin E) antioxidant levels and reduced tubular damage, restoring kidney morphology toward normal. Conclusion In conclusion, this study demonstrates the promising potential of fucosterol as a natural renin inhibitor for the treatment of diabetic kidney disease (DKD).