Renoprotective Potential of Robustaflavone Against Diabetes Induced Kidney Damage Via Regulating Oxidative Stress, Inflammation and Apoptosis

Diabetes mellitus (DM) is considered a persistent metabolic disorder in humans and animals that impacts more than 170 million people around the world.DM is associated with nephrotoxicity through ROS overproduction.Robustaflavone (RF) is a bioactive biflavonoid sourced from Nandina domestica.This work was carried out to investigate the therapeutic potential of RF against DM-provoked renal injury in rats.Albino rats were portioned into 4 treatment-groups each having 12 rats as follows: Control, DM (65mg/kg), DM + RF (65mg/kg+150mg/kg), and RF (150mg/kg).Current study outcomes displayed that DM-induction increased the levels of glucose, HbA1c, inflammatory, pro-apoptotic, renal injury and oxidative stress markers, while lowering the activities of antioxidants as well as insulin and anti-apoptotic marker levels.Moreover, DM induction instigated numerous severe histological anomalies in renal tissues.However, RF lowered the glucose and HbA1c levels while upregulating the insulin concentration.RF administration enhanced the enzymatic activities of antioxidants, including glutathione peroxidase (GPx), superoxidase dismutase (SOD), glutathione S-transferase (GST), glutathione (GSH), catalase (CAT), and glutathione reductase (GSR) but malonaldehyde (MDA) level and reactive oxygen species (ROS) were lowered.RF administration also lowered the concentration of creatinine, urea, NGAL, urinary proteins, kidney injury molecule-1 (KIM-1), and urobilinogen.Simultaneously, there was an increase in creatinine clearance concentration.Moreover, RF supplementation lowered inflammatory cytokines levels [nuclear factor-kappa B (NF-κB), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and interleukin one beta (IL-1β)].RF administration also lowered pro-apoptotic markers (Bax & Caspase-3) levels, while increasing anti-apoptotic marker (Bcl-2) levels and enhancing histological architecture of renal tissues.These outcomes demonstrate that RF confers significant protection against DM-induced renal injury via targeting oxidative stress, inflammatory and apoptotic pathway.