Renal Protective Effect of Boeravinone B against Diabetic Nephropathy Rats via Inhibition of The Inflammatory and JAK2/STAT3 Signalling Pathway

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorlycontrolled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocytedamage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluatethe nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore theunderlying mechanism.Materials and Methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) toinduce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, andorgan weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levelswere determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the ratswere sacrificed and their renal tissues were removed for histopathological assessment.Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepaticweights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine(Cr) and, albumin. There was a decrease (P 0.001) in histomorphological parameters such as kidney hypertrophyindex (KHI), mean glomerular volume (MGV), foot process fusion ratio (FPFR), and glomerular basement membranethickness (GBMT) after treatment with BB. In addition, this treatment improved the levels of renal podocin, renal CD2-associated protein (CD2AP) and suppressed hepatic parameter levels. BB treatment (P 0.001) altered antioxidantparameters and cytokine levels, and suppressed mRNA expressions of JAK2, STAT3, RAGE, KIM-1, NAGL, andS100A8.Conclusion: Administration of BB showed renal protective effects against STZ-induced DN in rats via the reduction ofoxidative stress and inflammatory reactions.