Title: Pomegranate peel ellagitannins ameliorate fructose-induced metabolic dysfunction in rats: Potential mechanisms of action
Abstract:
Pomegranate fruit is recognized for its potential benefits to oxidative and vascular health, effects that have been partly attributed to its ellagitannin constituents. However, whether pomegranate ellagitannins can attenuate the adverse metabolic effects associated with excessive consumption of added sugars, such as fructose and sucrose, remains unclear. This study investigated the ameliorative effects of pomegranate peel ellagitannins on fructose-induced metabolic alterations in rats. An ellagitannin-rich fraction was recovered from the peel of Punica granatum L. (Wonderful cultivar) using Amberlite XAD16N resin and characterized by LC–MS. Sprague–Dawley rats received a 20% fructose solution as a replacement for drinking water for 6 weeks, with or without oral administration of the ellagitannin-rich fraction (200 mg/kg body weight). Food intake, body weight, blood glucose and lipid profiles were assessed, followed by determination of insulin levels, glycogen content, oxidative stress and inflammatory markers, hepatic histology, and HOMA-IR. Hepatic phosphorylation of Akt and expression of phospho-PI3K were also evaluated.
Fructose consumption reduced food intake and increased body weight gain, while elevating insulin levels and impairing glucose tolerance (AUC, 246 vs. 208 mg·h/dL) and insulin sensitivity (HOMA-IR, 5.8 vs. 2.0). Fructose also induced dyslipidaemia, characterized by increased triglycerides (4.2 vs. 1.7 mmol/L) and LDL-cholesterol (3.0 vs. 1.4 mmol/L), together with reduced HDL-cholesterol (0.4 vs. 0.8 mmol/L). These metabolic alterations were accompanied by hepatic histopathological abnormalities, increased inflammation, as indicated by elevated IL-1β, and enhanced hepatic and systemic oxidative stress. Treatment with the ellagitannin-rich fraction improved glucose tolerance (AUC, 230 mg·h/dL) and insulin sensitivity (HOMA-IR, 4.0), accompanied by enhanced hepatic Akt phosphorylation and phospho-PI3K expression. It also improved the lipid profile, reducing triglycerides and LDL-cholesterol and increasing HDL-cholesterol (3.7, 1.9 and 0.6 mmol/L, respectively), while attenuating hepatic histopathological alterations and inflammation. Furthermore, treatment reduced lipid peroxidation and enhanced hepatic superoxide dismutase and catalase activities. LC–MS analysis identified several bioactive ellagitannins, including punicalagin, corilagin and pedunculagin, together with catechins. Overall, pomegranate peel ellagitannins attenuated fructose-induced insulin resistance, dyslipidaemia, inflammation and oxidative stress, potentially through modulation of PI3K/Akt-mediated insulin signalling and antioxidant defence. These findings support pomegranate peel ellagitannins as promising dietary polyphenols for mitigating sugar-induced metabolic and oxidative disturbances.
