Protective Effects of Stevia rebaudiana Leaf Extract on Cardio-Renal and Vascular Dysfunction in L-NAME-Induced Hypertensive Rats via Reduction of Oxidative Stress and Inflammation

El- Gammal, Nada A.; El- Senosi, Yakout A.; Mahfouz, Mohamed K.; Abd El-Mageid, Afaf D.; Mohammed, Mona A.; Fathy, Khaled; Marghani, Basma H.; Sedik, Ahmed A.

doi:10.21608/ejchem.2025.417672.12246

Protective Effects of Stevia rebaudiana Leaf Extract on Cardio-Renal and Vascular Dysfunction in L-NAME-Induced Hypertensive Rats via Reduction of Oxidative Stress and Inflammation

Document Type : Original Article

Authors

¹ Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Benha University, Benha, Egypt

² Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, El- Buhouth St., Dokki, Cairo, Egypt

³ Electron Microscopy Unit, Mansoura University, El Mansoura, Egypt

⁴ Department of Biochemistry, Physiology, and Pharmacology, Faculty of Veterinary Medicine, King Salman International University, South of Sinaa, Egypt

⁵ Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, El- Buhouth St., Dokki, Cairo, Egypt

10.21608/ejchem.2025.417672.12246

Abstract

Abstract

Background: Hypertension (HTN) is a major contributor to cardiovascular and renal disorders, with oxidative stress and endothelial dysfunction as key mechanisms.

Objective: Stevia rebaudiana (S. rebaudiana), a plant with antioxidant and anti-inflammatory features, was evaluated for its protective effects in an L-NAME–induced hypertensive rat model.

Brief Methods: Thirty-two male Sprague–Dawley rats were randomly assigned to four groups (n = 8): Control (standard diet), L-NAME (40 mg/kg/day), L-NAME + High Dose S. rebaudiana (500 mg/kg/day), and L-NAME + Low Dose S. rebaudiana (250 mg/kg/day). Phytochemical profiling was performed via HPLC and LC–MS, and antioxidant activity was assessed. Blood pressure, oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH)), nitric oxide levels, ACE activity, inflammatory cytokines (IL-6, TNF-α), and apoptotic markers (caspase-3, Bcl-2) were measured, alongside histopathological examination of heart, aorta, and kidney tissues.

Key Results: S. rebaudiana treatment produced dose-dependent reductions in blood pressure, restored nitric oxide levels, decreased MDA, increased GSH, downregulated IL-6, TNF-α, and caspase-3, and upregulated Bcl-2. Histology confirmed preservation of tissue structure.

Concise conclusion: S. rebaudiana provides cardio-renal protection by modulating oxidative stress, inflammation, and apoptosis, supporting its potential as a natural therapy for hypertension-related complications.

Keywords