Synthesis and protective effect of 7-O-thiazole Oroxylin A derivative against diabetic nephropathy in streptozotocin-induced diabetes in Wistar rats

Abstract

This study synthesized a 7-O-thiazole derivative of Oroxylin A (compound 1) to assess its potential in treating diabetic nephropathy (DN) using high-fat diet (HFD) and streptozotocin (STZ) induced pancreatic β-cell toxicity in Wistar rats. The synthesis yielded a compound of high purity, which was tested for bioactivity in DN. The effects of compound 1 on body weight and fasting blood glucose levels were examined, revealing a positive impact on body weight and a dose-dependent reduction in glucose levels. Liver function markers (ALP, AST, and ALT) and renal function indicators (BUN, serum creatinine, and CCr) showed significant improvement, alongside enhancements in lipid profiles, including reductions in TC, TG, VLDL, and an increase in HDL. Compound 1 also reduced proteinuria, oxidative stress, and pro-inflammatory cytokine production in the kidneys. Pharmacokinetic analysis indicated that compound 1 is more bioavailable and less prone to metabolic inactivation than Oroxylin A, suggesting that thiazole derivatization prevents metabolic deactivation. These findings demonstrate the potential of the 7-O-thiazole derivative of Oroxylin A as a protective agent against diabetic nephropathy through multiple therapeutic actions.