Modulation of KIM-1/TGF-β1 signaling pathway by Ocimum gratissimum leaf flavonoid-rich extracts in the kidneys of streptozotocin-induced diabetic rats

Diabetic nephropathy, one of the most prevalent complications of diabetes mellitus, is driven by hyperglycemia-induced overproduction of reactive oxygen species (ROS) and pro-inflammatory cytokines, ultimately resulting in structural and functional renal impairment. This study evaluated the renoprotective effects of a flavonoid-rich extract derived from Ocimum gratissimum leaves in a streptozotocin (STZ)-induced diabetic rat model. Type 2 diabetes mellitus was induced by intraperitoneal administration of STZ (45 mg/kg body weight) following one week of 20% (w/v) fructose supplementation. Rats were randomly assigned to five groups (n = 8): negative control (NC), diabetic control (DC), diabetic rats treated with low-dose (150 mg/kg) and high dose (300 mg/kg) O. gratissimum flavonoid-rich extract (LDOGFL and HDOGFL, respectively), and metformintreated diabetic rats (200 mg/kg; MET). On day 22, blood and kidney tissue was collected for assessment of redox status, inflammatory biomarkers, kidney function indices (creatinine, urea, and uric acid), electrolyte concentrations, kidney-specific acid phosphatase (ACP) and alkaline phosphatase (ALP) activities, mRNA expression of KIM-1 and TGF-β1, and histopathological changes. Treatment with LDOGFL, HDOGFL, or MET significantly (p < 0.05) improved redox balance, reduced inflammatory cytokines, and lowered creatinine, urea, and uric acid levels compared with untreated diabetic controls. Electrolyte profiles and ACP/ALP activities increased significantly (p < 0.05), whereas mRNA expression of KIM-1 and TGF-β1 was markedly downregulated. Histopathological examination revealed enhanced epithelial cell integrity within renal convoluted tubules and glomeruli in treated groups. Collectively, these findings indicate that the flavonoid-rich extract of O. gratissimum leaves confers renoprotective benefits in diabetic nephropathy by attenuating oxidative stress, suppressing inflammation, and improving renal function.