eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-03-30 23 1 422 437 10.13005/bbra/3509 58652 article Kalisetty Lakshmi Sowjanya 1 Gujjula Koteswara Reddy 1 Neelagiri Chandrasekharnath 2 Addepally Uma 2 Department of Bio-technology, K L E F Deemed to be University, Vijayawada, Andhra Pradesh, India Department of Bio Technology, Centre for Innovative Research, JNTUH University College of Engineering, Science & Technology Hyderabad (UCESTH), Telangana, India. Endothelial dysfunction is a critical precursor to vascular complications in type 2 diabetes, largely driven by oxidative stress, impaired nitric oxide (NO) bioavailability, and inflammation. This study evaluated the protective effects of phenolic-rich Moringa oleifera extract (PMOE) against streptozotocin-nicotinamide-induced endothelial dysfunction in rats, focusing on the arginase 1/eNOS axis and the Nrf-2 pathway. Male Wistar rats were divided into four groups (n = 6): normal control, diabetic control, and diabetic rats treated with PMOE (250 mg/kg or 500 mg/kg) orally for 45 days. Diabetic controls exhibited significant hyperglycemia, elevated HbA1c, reduced serum insulin, increased blood pressure, and higher serum arginase activity compared to normal rats. These changes were accompanied by reduced NO levels, decreased NO synthase (NOS) activity, and enhanced reactive oxygen species (ROS) generation with concomitant depletion of endogenous antioxidants (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase). PMOE administration significantly lowered fasting glucose, HbA1c, blood pressure, and arginase activity while restoring insulin, NO concentrations, NOS activity, and antioxidant status in a dose-dependent manner. RT-qPCR analysis revealed that PMOE suppressed ARG1, VCAM-1, and ICAM-1 expression, while upregulating eNOS, Nrf-2, HO-1, and NQO1 transcripts. Histopathological examination confirmed severe vascular disruption in diabetic controls, whereas PMOE treatment preserved endothelial integrity and medial structure, particularly at the higher dose, which closely resembled normal controls. These findings indicate that PMOE mitigates diabetes-induced endothelial dysfunction by reducing arginase activity, restoring NO bioavailability, and activating the Nrf-2 antioxidant pathway. https://www.biotech-asia.org/vol23no1/protective-effects-of-phenolic-rich-moringa-oleifera-extract-on-streptozotocin-nicotinamide-induced-endothelial-dysfunction-involvement-of-arginase-1-and-nrf2-mediated-antioxidant-pathways/ Arginase 1; Endothelial dysfunction; Moringa oleifera; Nrf-2 pathway; Oxidative stress