THERAPEUTIC EFFICACY OF CHLOROGENIC ACID IN ATTENUATING DIABETIC NEPHROPATHY VIA MODULATION OF ANG II-MEDIATED MOLECULAR PATHWAYS

Abstract

Diabetes mellitus (DM) is a long-standing metabolic condition with serious complications, of which diabetic nephropathy (DN) is still one of the leading causes of end-stage renal disease (ESRD) globally. This current research sought to investigate the curative efficacy of chlorogenic acid (CGA), a natural polyphenolic compound in coffee and fruits, in treating DN by modulation of the Angiotensin II (Ang II)-mediated mechanisms. Male Wistar rats were induced to diabetes with streptozotocin (STZ, 65 mg/kg) and nicotinamide (NA, 230 mg/kg) and then CGA (40 mg/kg) was given orally for eight weeks. Biochemical, urine, and histological parameters were measured together with the estimation of inflammatory (TNF-α, IL-1β), oxidative stress markers (SOD, GSH, MDA), and serum Ang II levels by ELISA. Findings showed that CGA significantly reduced fasting blood glucose, HbA1c, serum creatinine, and blood urea nitrogen levels but increased antioxidant status and renal function. Treatment with CGA also reduced TNF-α and IL-1β markedly, enhanced SOD and GSH activity, and inhibited Ang II expression, leading to diminished renal inflammation and oxidative stress. Histopathological observations showed that CGA restored glomerular architecture and decreased tubular damage compared to diabetic controls. These findings suggest that CGA is an effective safeguard against STZ–NA-induced renal injury by suppressing Ang II-induced inflammatory and oxidative processes. Overall, chlorogenic acid possesses potent nephroprotective and anti-diabetic effects, making it a promising natural drug candidate in the therapy of diabetic nephropathy through the modulation of the renin–angiotensin system and associated molecular processes.