Pleiotrosepic ameliorative effects of ellagitannin geraniin against metabolic syndrome induced by high-fat diet in rats

Abstract Objective: Metabolic syndrome (MetS) which is a multiplex risk factor for cardiovascular disease and type 2 diabetes, is increasingly prevalent worldwide. Ellagitannin geraniin, a polyphenol found in the rind of rambutan (Nephelium lappaceum), has demonstrated therapeutic effects against metabolism dysfunction. This study aimed to characterise the metabolic effects and possible mechanism of geraniin in MetS rats induced by high-fat diet (HFD). Research Methods & Procedures: MetS was induced in Sprague Dawley rats with HFD, followed by oral gavage of geraniin (25 mg/kg/day) for 4 weeks. The outcomes of geraniin-treated rats were compared to untreated rats on either control diet or HFD and MetS rats treated with metformin (200 mg/kg/day). Results: The supplementation of geraniin ameliorated multiple metabolic abnormalities caused by HFD, including hypertension, impaired glucose and lipid metabolism, ectopic fat deposition in the visceral fat and liver, and disturbed antioxidant mechanism and inflammatory response. The benefits conferred by geraniin were comparable to metformin. Transcriptomic analysis revealed a profound influence of geraniin on the hepatic expression profiles. The lipid and steroid metabolic processes which were aberrantly activated by HFD were suppressed by geraniin. Based on the differential transcriptomes, geraniin also exerted a significant modulatory effect on the expression of mitochondrion-related genes, potentially influencing the mitochondrial activity and leading to the observed beneficial effects. Conclusion: Geraniin supplementation mitigated metabolic anomalies of MetS in rats, making it an attractive drug candidate for further investigation.