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.
J Ethnopharmacol. 2018 Jun 28;220:67-74. doi: 10.1016/j.jep.2018.03.029. Epub 2018 Mar 28.
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.
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.
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.
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.
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.
石榴果实被认为是某些传统医学体系中的抗糖尿病药物。此外,石榴多酚是众所周知的强大抗氧化剂,具有有益的作用,如减少氧化/炎症应激,增加保护性信号,如抗氧化酶、神经营养因子和细胞保护蛋白。
这项工作评估了石榴汁、其主要多酚类物质如鞣花酸和安石榴甙,以及其主要代谢物尿石素 A 对肥胖和糖尿病等代谢性疾病的生理和药理靶点的影响。
为此,在无细胞体系中进行了脂肪酶、α-葡萄糖苷酶和二肽基肽酶-4 的酶抑制生物测定。同样,使用来自 3T3-L1 细胞的脂肪细胞来研究鞣花酸、安石榴甙和尿石素 A 对脂肪细胞分化和甘油三酯(TG)积累的影响。
石榴汁、鞣花酸、安石榴甙和尿石素 A 均能抑制脂肪酶、α-葡萄糖苷酶和二肽基肽酶-4。此外,所有测试的化合物但明显的代谢物尿石素 A 以剂量依赖的方式显示出抗脂肪生成特性,因为它们显著减少了 TG 积累和与脂肪细胞形成相关的基因表达,如脂肪细胞分化相关蛋白 1(adiponectin)、过氧化物酶体增殖物激活受体γ(PPARγ)、葡萄糖转运蛋白 4(GLUT4)和脂肪酸结合蛋白 4(FABP4)。
这些结果可以从分子角度解释石榴在预防肥胖、糖尿病和相关并发症等代谢相关疾病方面的有益作用和传统用途。