Comparison <i>of Hibiscus sabdariffa L.</i> extract and hydrochlorothiazide as adjuncts to Valsartan in managing hypertension in type 2 diabetic nephropathy: A randomized clinical trial.

Objective: L. extract (HSE) as a supplemental therapy with valsartan for type 2 diabetic patients with nephropathy and its underlying biological functions were investigated in this study. Materials and Methods: This clinical trial took place in Gorgan, Iran with 70 diabetic nephropathy patients who had hypertension. The participants were divided into two groups: The HSE group which received 500 mg HSE along with valsartan 40 mg twice daily over three months (n=35) and the control group which received valsartan plus hydrochlorothiazide 12.5 mg (n=35). The study measured blood pressure levels with additional assessments of microalbuminuria, proteinuria, and glomerular filtration rate (GFR) alongside lipid profile analysis, and hemoglobin A1c (HbA1c), fasting blood glucose (FBS), and electrolyte tests. Molecular docking simulations tested HSE compounds as potential inhibitors of sodium-glucose cotransporter-2 (SGLT2), dipeptidyl peptidase-4 (DPP-4), glucagon-like peptide-1 (GLP-1), and Receptor for advanced glycation end products (RAGE). Results: Both groups showed improvements, but HSE had a greater impact on kidney function and lipid levels, while control group was more effective in lowering blood pressure and improving glucose metabolism. Docking analysis revealed that cyanidin 3-O-beta-D-sambubioside and tiliroside strongly interacted with targets, suggesting a role in blood glucose regulation and insulin secretion. Conclusion: HSE demonstrates the potential to help type 2 diabetic nephropathy patients by modifying renin-angiotensin-aldosterone system activity carbohydrate digestion processes and lipid metabolism which reduces diabetic complications risks.