Hydroethanol Leaf Extract of Ruellia tuberosa Modulates Renal NF-κB/Nrf2 Axis in High-Fat Diet/Streptozotocin-Induced Type 2 Diabetic Rats

Type 2 diabetes mellitus (T2DM) is a major metabolic disorder frequently associated with diabetic nephropathy, a condition driven by persistent inflammation and oxidative stress. Although, Ruellia tuberosa L. has been traditionally used for diabetes management and reported to exert beneficial metabolic effects, its regulatory influence on renal NF-κB/Nrf2 signaling pathways remains poorly understood. This study aimed to investigate the effects of oral administration of hydroethanol leaf extract of Ruellia tuberosa on metabolic parameters and renal inflammatory–antioxidant signaling in a high-fat diet (HFD) and streptozotocin (STZ)–induced rat model of T2DM. Eighteen (18) male Sprague–Dawley rats were randomly assigned into three groups of six animals per group; control, diabetic, and extract-treated groups (300 mg/kg body weight). Diabetes was induced by eight weeks of HFD followed by a single intraperitoneal injection of STZ (40 mg/kg). Body weight and fasting blood glucose levels were assessed, and renal NF-κB and Nrf2 expression were evaluated using immunohistochemistry with mean gray value quantification. Diabetic rats exhibited increased body weight, elevated fasting blood glucose levels, enhanced renal NF-κB expression, and reduced Nrf2 expression compared with controls (p < 0.05). Treatment with hydroethanol leaf extract of Ruellia tuberosa significantly improved metabolic parameters, suppressed NF-κB activation, and enhanced renal Nrf2 expression (p < 0.05). These findings indicate that hydroethanol leaf extract of Ruellia tuberosa exerts preventive renoprotective effects by restoring the balance between inflammatory and antioxidant signaling pathways, highlighting its potential as a natural candidate for mitigating diabetes-associated renal complications.