Therapeutic Potential of Cinnamic Acid as an SGLT2 Inhibitor in Mitigating Diabetic Nephropathy in a Rat Model of Type 2 Diabetes

This study investigates the renal protective effects of cinnamic acid (CA) in a Type 2 diabetes mellitus (T2DM) rat model induced by high-fat diet (HFD) and streptozotocin (STZ), with a focus on its potential as a natural hypoglycemic agent and SGLT2 inhibitor. In a randomized design, five groups of rats (n = 8) were administered different treatments for 8 weeks: Control, Control + CA (40 mg/kg), T2DM, T2DM + CA (20 mg/kg), and T2DM + CA (40 mg/kg). CA treatment (20 and 40 mg/kg) significantly improved the glomerular and tubular structure in T2DM group, with normal features observed at the highest dose. In a dose-dependent manner, CA doses also reduced fasting glucose, HbA1c, and HOMA-IR in T2DM group, alongside enhanced total antioxidant capacity (TAC). Notably, renal function was significantly improved with CA treatment at both doses, as evidenced by reduced urine volume, serum BUN, creatinine, and urinary albumin. Furthermore, CA markedly reduced glomerular injury markers (NAG, A1M, F-LAP) and tubular injury biomarkers (transferrin, fibronectin, ceruloplasmin). Additionally, mRNA expression of SGLT, TLR4, and NF-kB was significantly reduced in CA-treated T2DM group. These findings suggest that CA exerts a multifaceted protective effect against renal dysfunction in T2DM by acting as an SGLT2 inhibitor.