Furan-based chalcone protects β-cell damage and improves glucose uptake in alloxan-induced zebrafish diabetic model via influencing Peroxisome Proliferator-Activated Receptor Agonists (PPAR-γ) signaling

Abstract

Diabetes mellitus, a major global health concern, is emerging as the primary human disease in the twenty-first century, with beta cell damage and dysfunction playing a critical role, particularly in type 2 diabetes. Inflammation and oxidative stress are critical in beta cell damage associated with type 2 diabetes. Current anti-diabetic drugs frequently fail to achieve intended efficacy and are associated with side effects, necessitating novel treatments that target the underlying pathophysiology. Chalcones have gained popularity due to their varied biological activity. In this study, we use an alloxan-induced beta cell damage zebrafish model to evaluate the potential anti-inflammatory and beta cell protective properties of DKO3 ((E)-1-(5-methylfuran-2-yl)-3-(3-nitrophenyl) prop-2-en-1-one), a synthetic chalcone. DKO3 exhibits dose-dependent anti-inflammatory and α-glucosidase activity in vitro. DKO3 reduced oxidative stress, restored antioxidant enzyme levels, decreased lipid peroxidation and cellular damage, inhibited cellular apoptosis, and regulated proinflammatory cytokine levels. It prevented alloxan-induced beta cell damage, increased PPAR-γ expression, and influenced insulin-sensitive genes such as SIRT1, GLUT2, GSK3, and INSA. These findings underscore DKO3's potential therapeutic utility in managing diabetes and related inflammatory conditions.