Aucubin Ameliorates Alloxan-Induced Diabetic Liver Injury in Association with Modulation of the Nrf2/HO-1 Antioxidant...

Diabetes mellitus is associated with progressive hepatic injury driven by oxidative stress, inflammation, and apoptosis. Aucubin, a natural iridoid glycoside, possesses potent antioxidant and anti-inflammatory activities; however, its hepatoprotective mechanisms in diabetic liver injury remain unclear. This study investigated the protective effects of aucubin against alloxan-induced diabetic hepatic injury and the underlying molecular mechanisms. Male albino rats were assigned to five groups: normal control, alloxan-induced diabetic, diabetic treated with metformin (150 mg/kg), and diabetic treated with aucubin (25 or 50 mg/kg) for 28 days. We evaluated body weight, fasting blood glucose, liver function, lipid profile, oxidative stress biomarkers, inflammatory cytokines, and hepatic expression of Nrf2, HO-1, NF-κB p65, Bax, and Bcl-2, along with histopathological and immunohistochemical examinations. Alloxan induced marked hyperglycemia, weight loss, hepatic dysfunction, dyslipidemia, oxidative stress, inflammation, and apoptosis. Aucubin significantly ameliorated these alterations, with the 50 mg/kg dose generally showing greater effects than the 25 mg/kg dose. Aucubin improved liver function, ameliorated dyslipidemia, reduced lipid peroxidation, enhanced antioxidant defenses, increased Nrf2 and HO-1 expression, attenuated NF-κB p65 expression and pro-inflammatory cytokines, favorably modulated the Bax/Bcl-2 balance, preserved hepatic architecture, and increased Ki-67 immunoreactivity, indicating enhanced cellular proliferative activity. These findings indicate that aucubin is associated with improved hepatic antioxidant, inflammatory, apoptotic, and metabolic status in alloxan-induced diabetic rats.