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Evaluation of Viburnum opulus L. Fruit Phenolics Cytoprotective Potential on Insulinoma MIN6 Cells Relevant for Diabetes Mellitus and Obesity.
Antioxidants ( IF 7 ) Pub Date : 2020-05-16 , DOI: 10.3390/antiox9050433
Małgorzata Zakłos-Szyda 1 , Agnieszka Kowalska-Baron 2 , Nina Pietrzyk 1 , Anna Drzazga 1 , Anna Podsędek 1
Affiliation  

In this study, the influence of guelder rose (Viburnum opulus) fruit fresh juice (FJ) and a phenolic-rich fraction (PRF) isolated from juice on mice insulinoma MIN6 cells activities was investigated. Extracts were able to decrease intracellular oxidative stress at the highest non-cytotoxic concentrations. They induced glucagon-like peptide-1 (GLP-1) secretion in the presence of an elevated glucose concentration, and they inhibited in vitro activity of the dipeptidyl peptidase-4 (DPP4) enzyme. Nonetheless, inhibition of glucose-stimulated insulin secretion was detected, which was accompanied by a decrease of cellular membrane fluidity and hyperpolarization effect. In addition, the increase of free fatty acid uptake and accumulation of lipid droplets in MIN6 cells were observed. Elevated extract concentrations induced cell apoptosis through the intrinsic mitochondrial pathway with activation of initiatory caspase-9 and downstream caspases-3/7. The fluorescence-quenching studies indicated that PRF extract has binding affinity to human serum albumin, which is one of the factors determining drug bioavailability. Taken together, despite the cytoprotective activity against generated intracellular oxidative stress, V. opulus revealed potential toxic effects as well as decreased insulin secretion from MIN6 cells. These findings are relevant in understanding V. opulus limitations in developing diet supplements designed for the prevention and treatment of postprandial glucose elevation.

中文翻译:

评估荚莲属植物酚类物质对与糖尿病和肥胖相关的胰岛素瘤 MIN6 细胞的细胞保护潜力。

在本研究中,研究了琼脂(Viburnum opulus)水果新鲜果汁(FJ)和从果汁中分离出的富含酚类成分(PRF)对小鼠胰岛素瘤 MIN6 细胞活性的影响。提取物能够在最高的非细胞毒性浓度下减少细胞内氧化应激。它们在葡萄糖浓度升高的情况下诱导胰高血糖素样肽 1 (GLP-1) 分泌,并抑制二肽基肽酶 4 (DPP4) 的体外活性。尽管如此,检测到葡萄糖刺激的胰岛素分泌受到抑制,伴随着细胞膜流动性和超极化效应的降低。此外,还观察到MIN6细胞中游离脂肪酸摄取的增加和脂滴积累的增加。升高的提取物浓度通过内在线粒体途径诱导细胞凋亡,激活起始 caspase-9 和下游 caspase-3/7。荧光猝灭研究表明,PRF提取物与人血清白蛋白具有结合亲和力,这是决定药物生物利用度的因素之一。总而言之,尽管 V. opulus 对产生的细胞内氧化应激具有细胞保护活性,但仍显示出潜在的毒性作用以及 MIN6 细胞的胰岛素分泌减少。这些发现有助于理解 V. opulus 在开发用于预防和治疗餐后血糖升高的膳食补充剂方面的局限性。
更新日期:2020-05-16
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