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Pomegranate polyphenols and urolithin A inhibit α-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells.
J Ethnopharmacol. 2018 Jun 28; 220:67-74.JE

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.

Authors+Show Affiliations

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.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.Departamento de Farmacología y Fisiología, Universidad de Zaragoza, Spain.Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, Villanueva de Gállego (Zaragoza) Spain. Electronic address: ilopez@usj.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29604377

Citation

Les, Francisco, et al. "Pomegranate Polyphenols and Urolithin a Inhibit Α-glucosidase, Dipeptidyl Peptidase-4, Lipase, Triglyceride Accumulation and Adipogenesis Related Genes in 3T3-L1 Adipocyte-like Cells." Journal of Ethnopharmacology, vol. 220, 2018, pp. 67-74.
Les F, Arbonés-Mainar JM, Valero MS, et al. Pomegranate polyphenols and urolithin A inhibit α-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells. J Ethnopharmacol. 2018;220:67-74.
Les, F., Arbonés-Mainar, J. M., Valero, M. S., & López, V. (2018). Pomegranate polyphenols and urolithin A inhibit α-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells. Journal of Ethnopharmacology, 220, 67-74. https://doi.org/10.1016/j.jep.2018.03.029
Les F, et al. Pomegranate Polyphenols and Urolithin a Inhibit Α-glucosidase, Dipeptidyl Peptidase-4, Lipase, Triglyceride Accumulation and Adipogenesis Related Genes in 3T3-L1 Adipocyte-like Cells. J Ethnopharmacol. 2018 Jun 28;220:67-74. PubMed PMID: 29604377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pomegranate polyphenols and urolithin A inhibit α-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells. AU - Les,Francisco, AU - Arbonés-Mainar,José Miguel, AU - Valero,Marta Sofía, AU - López,Víctor, Y1 - 2018/03/28/ PY - 2017/12/18/received PY - 2018/02/16/revised PY - 2018/03/23/accepted PY - 2018/4/1/pubmed PY - 2018/10/3/medline PY - 2018/4/1/entrez KW - 3T3-L1 KW - Dipeptidyl peptidase-4 KW - Ellagic acid (CAS: 476-66-4) KW - Lipase KW - Polyphenols KW - Punicalagin (CAS: 65995-63-3) KW - Urolithin A KW - Urolithin A (CAS: 1143-70-0) KW - α-glucosidase SP - 67 EP - 74 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 220 N2 - 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/29604377/Pomegranate_polyphenols_and_urolithin_A_inhibit_α_glucosidase_dipeptidyl_peptidase_4_lipase_triglyceride_accumulation_and_adipogenesis_related_genes_in_3T3_L1_adipocyte_like_cells_ DB - PRIME DP - Unbound Medicine ER -