Unravelling the Ameliorative Mechanisms of Ellagitannins From Pomegranate Peel on Fructose-Induced Detrimental Metabolic Alterations in Rats

Abstract

Pomegranate fruit is known to benefit oxidative and vascular health, which has been linked to some constituent ellagitannins. However, it remains unknown whether pomegranate ellagitannins can mitigate the detrimental metabolic alterations caused by added sugars like sucrose and fructose. Hence, this study investigated the ameliorative potential of pomegranate peel ellagitannins on fructose-induced metabolic alterations. An ellagitannin-rich fraction was recovered from the peel of pomegranate (Wonderful var.) using an Amberlite XAD16N resin. The fraction was subjected to LC–MS analysis. The fraction (200 mg/kg bw) was administered to Sprague–Dawley rats receiving 20% fructose solution in place of drinking water for 6 weeks. Food intake, body weight, blood glucose and blood lipids were measured. Thereafter, insulin level, glycogen content, oxidative stress and inflammatory markers, hepatic histology and HOMA-IR were determined. Hepatic Akt phosphorylation and phospho-PI3K expression were also determined. Fructose consumption suppressed food intake and increased weight gain. It further increased insulin levels and impaired glucose tolerance (AUC = 246 vs. 208 mg.h/dL) and insulin action (HOMA-IR = 5.8 vs. 2.0); altered blood lipid levels (triglycerides = 4.2 vs. 1.7 mmol/L; LDL-cholesterol = 3.0 vs. 1.4 mmol/L; HDL-cholesterol = 0.4 vs. 0.8 mmol/L); caused hepatic histological abnormalities and inflammation (IL-1β elevation) and increased hepatic and systemic oxidative stress. Ellagitannin treatment improved glucose tolerance (AUC = 230 mg.h/dL), insulin resistance (HOMA-IR = 4.0; improved hepatic Akt phosphorylation and phospho-PI3K expression), blood lipid profile (triglycerides, LDL-cholesterol and HDL-cholesterol = 3.7, 1.9 and 0.6 mmol/L, respectively), hepatic histology, inflammation and antioxidant status (reduced lipid peroxidation and increased SOD and catalase enzyme activity). LC–MS showed the presence of bioactive ellagitannins (punicalagin, corilagin and pendunculagin) and catechins. Ellagitannins from pomegranate peel mitigated against fructose-induced insulin resistance, dyslipidaemia, proinflammatory signalling and oxidative stress. Pomegranate peel ellagitannins may be useful dietary polyphenols to prevent or manage sugar-induced metabolic, cardiovascular and oxidative disorders.