Francisco Les1, José Miguel Arbonés-Mainar2, Marta Sofía Valero3, Víctor López4. 1. Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego (Zaragoza) Spain; Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Instituto de Investigacion Sanitaria (IIS) Aragon, Zaragoza, Spain. 2. Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Instituto de Investigacion Sanitaria (IIS) Aragon, Zaragoza, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain. 3. Departamento de Farmacología y Fisiología, Universidad de Zaragoza, Spain. 4. Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego (Zaragoza) Spain. Electronic address: ilopez@usj.es.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate fruit is considered an antidiabetic medicine in certain systems of traditional medicine. In addition, pomegranate polyphenols are known as powerful antioxidants with beneficial effects such as the reduction of oxidative / inflammatory stress and the increase of protective signalling such as antioxidant enzymes, neurotrophic factors and cytoprotective proteins. AIM OF THE STUDY: This work evaluates the effects of pomegranate juice, its main polyphenols known as ellagic acid and punicalagin, as well as its main metabolite urolithin A, on physiological and pharmacological targets of metabolic diseases such as obesity and diabetes. MATERIALS AND METHODS: For this purpose, enzyme inhibition bioassays of lipase, α-glucosidase and dipeptidyl peptidase-4 were carried out in cell-free systems. Similarly, adipocytes derived from 3T3-L1 cells were employed to study the effects of ellagic acid, punicalagin and urolithin A on adipocyte differentiation and triglyceride (TG) accumulation. RESULTS: Pomegranate juice, ellagic acid, punicalagin and urolithin A were able to inhibit lipase, α-glucosidase and dipeptidyl peptidase-4. Furthermore, all tested compounds but significantly the metabolite urolithin A displayed anti-adipogenic properties in a dose-dependent manner as they significantly reduced TG accumulation and gene expression related to adipocyte formation such as adiponectin, PPARγ, GLUT4, and FABP4 in 3T3-L1 adipocytes. CONCLUSION: These results may explain from a molecular perspective the beneficial effects and traditional use of pomegranate in the prevention of metabolic-associated disorders such as obesity, diabetes and related complications.
ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate fruit is considered an antidiabetic medicine in certain systems of traditional medicine. In addition, pomegranatepolyphenols are known as powerful antioxidants with beneficial effects such as the reduction of oxidative / inflammatory stress and the increase of protective signalling such as antioxidant enzymes, neurotrophic factors and cytoprotective proteins. AIM OF THE STUDY: This work evaluates the effects of pomegranate juice, its main polyphenols known as ellagic acid and punicalagin, as well as its main metabolite urolithin A, on physiological and pharmacological targets of metabolic diseases such as obesity and diabetes. MATERIALS AND METHODS: For this purpose, enzyme inhibition bioassays of lipase, α-glucosidase and dipeptidyl peptidase-4 were carried out in cell-free systems. Similarly, adipocytes derived from 3T3-L1 cells were employed to study the effects of ellagic acid, punicalagin and urolithin A on adipocyte differentiation and triglyceride (TG) accumulation. RESULTS:Pomegranate juice, ellagic acid, punicalagin and urolithin A were able to inhibit lipase, α-glucosidase and dipeptidyl peptidase-4. Furthermore, all tested compounds but significantly the metabolite urolithin A displayed anti-adipogenic properties in a dose-dependent manner as they significantly reduced TG accumulation and gene expression related to adipocyte formation such as adiponectin, PPARγ, GLUT4, and FABP4 in 3T3-L1 adipocytes. CONCLUSION: These results may explain from a molecular perspective the beneficial effects and traditional use of pomegranate in the prevention of metabolic-associated disorders such as obesity, diabetes and related complications.
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