Food Research Center-(FoRC-CEPID) and Department of Food Science and Nutrition, School of Pharmaceutical Science, University of São Paulo, Av. Prof Lineu Prestes 580, Bloco 14, 05508-900 São Paulo, SP, Brazil.
Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, 451 East Health Sciences Drive, 95616, Davis, California, USA and Unité de Nutrition Humaine, INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Food Funct. 2020 Oct 21;11(10):8612-8624. doi: 10.1039/d0fo01839b.
Cholesterol is one of the triggers of oxidative stress in the pancreatic-β cell, generating high levels of reactive oxygen species, which leads to impairment of insulin synthesis and secretion. Bioactive compounds, such as citrus flavanones, which possess anti-inflammatory and antioxidant activities, could reduce oxidative stress in β-cells and improve their function. We describe for the first time the protective effects of the phase-II flavanone metabolites [naringenin 7-O-glucuronide, hesperetin 3'-O-glucuronide, and hesperetin 7-O-glucuronide], and two flavanones-catabolites derived from gut microbiota metabolism [hippuric acid and 3-(4-hydroxyphenyl)propionic acid], on pancreatic β-cell line MIN6 under oxidative stress, at physiologically relevant concentration. Cholesterol reduced cell viability in a dose and time-dependent manner, with an improvement in the presence of the metabolites. Moreover, flavanone metabolites attenuated oxidative stress by reducing levels of lipid peroxides, superoxide anions, and hydrogen peroxide. In response to the reduction of reactive oxygen species, a decrease in superoxide dismutase and glutathione peroxidase activities was observed; these activities were elevated by cholesterol. Moreover, all the flavanone metabolites improved mitochondrial function and insulin secretion, and reduced apoptosis. Flavanone metabolites were found uptake by β-cells, and therefore could be responsible for the observed protective effects. These results demonstrated that circulating phase-II hesperetin and naringenin metabolites, and also phenolics derived from gut microbiota, protect pancreatic-β cells against oxidative stress, leading to an improvement in β-cell function and could be the bioactive molecules derived from the citrus consumption.
胆固醇是胰腺β细胞氧化应激的触发因素之一，它会产生高水平的活性氧，导致胰岛素合成和分泌受损。具有抗炎和抗氧化活性的生物活性化合物，如柑橘类黄酮，可减少β细胞中的氧化应激并改善其功能。我们首次描述了 II 相黄酮类代谢物[柚皮苷 7-O-葡萄糖醛酸、橙皮苷 3'-O-葡萄糖醛酸和橙皮苷 7-O-葡萄糖醛酸]以及两种源自肠道微生物群代谢的黄酮类化合物-代谢物[马尿酸和 3-(4-羟苯基)丙酸]对 MIN6 胰腺β细胞系在氧化应激下的保护作用，其浓度在生理相关范围内。胆固醇以剂量和时间依赖的方式降低细胞活力，而代谢物的存在则改善了细胞活力。此外，黄酮类代谢物通过降低脂质过氧化物、超氧阴离子和过氧化氢水平来减轻氧化应激。为了应对活性氧的减少，观察到超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低；胆固醇会增加这些活性。此外，所有的黄酮类代谢物都改善了线粒体功能和胰岛素分泌，并减少了细胞凋亡。发现黄酮类代谢物被β细胞摄取，因此可能是观察到的保护作用的原因。这些结果表明，循环中的 II 相橙皮苷和柚皮苷代谢物以及源自肠道微生物群的酚类物质可保护胰腺β细胞免受氧化应激，从而改善β细胞功能，它们可能是源自柑橘类水果消费的生物活性分子。
