特级初榨橄榄油中的酚类提取物抑制二肽基肽酶IV活性：体外、细胞及计算机辅助分子模拟研究

Phenolic Extracts from Extra Virgin Olive Oils Inhibit Dipeptidyl Peptidase IV Activity: In Vitro, Cellular, and In Silico Molecular Modeling Investigations.

作者信息

Lammi Carmen, Bartolomei Martina, Bollati Carlotta, Cecchi Lorenzo, Bellumori Maria, Sabato Emanuela, Giulio Vistoli, Mulinacci Nadia, Arnoldi Anna

机构信息

Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy.

Department of Neuroscience, Psychology, Drug and Child Health, Pharmaceutical and Nutraceutical Section, University of Florence, 50019 Florence, Italy.

出版信息

Antioxidants (Basel). 2021 Jul 16;10(7):1133. doi: 10.3390/antiox10071133.

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± 6.1, 37.9 ± 2.4, 57.8 ± 2.9, and 81 ± 1.4% for BUO and by 5.4 ± 1.7, 8.9 ± 0.4, 28.4 ± 7.2, 52 ± 1.3, and 77.5 ± 3.5% for OMN. Moreover, both BUO and OMN reduced the DPP-IV activity expressed by Caco-2 cells by 2.9 ± 0.7, 44.4 ± 0.7, 61.2 ± 1.8, and 85 ± 4.2% and by 3 ± 1.9, 35 ± 9.4, 60 ± 7.2, and 82 ± 2.8%, respectively, at the same doses. The concentration of the most abundant and representative secoiridoids within both extracts was analyzed by nuclear magnetic resonance (H-NMR). Oleuropein, oleacein, oleocanthal, hydroxytyrosol, and tyrosol, tested alone, reduced the DPP-IV activity, with IC of 472.3 ± 21.7, 187 ± 11.4, 354.5 ± 12.7, 741.6 ± 35.7, and 1112 ± 55.6 µM, respectively. Finally, in silico molecular docking simulations permitted the study of the binding mode of these compounds.

两种特级初榨橄榄油（EVOO）酚类提取物（BUO和OMN）可调节二肽基肽酶-IV（DPP-IV）的活性。体外DPP-IV活性测定在1、10、100、500和1000μg/mL的浓度下进行，结果显示，BUO对DPP-IV活性的抑制呈剂量依赖性，抑制率分别为6.8±1.9%、17.4±6.1%、37.9±2.4%、57.8±2.9%和81±1.4%；OMN的抑制率分别为5.4±1.7%、8.9±0.4%、28.4±7.2%、52±1.3%和77.5±3.5%。此外，在相同剂量下，BUO和OMN分别使Caco-2细胞表达的DPP-IV活性降低了2.9±0.7%、44.4±0.7%、61.2±1.8%和85±4.2%，以及3±1.9%、35±9.4%、60±7.2%和82±2.8%。通过核磁共振（H-NMR）分析了两种提取物中最丰富且具代表性的裂环环烯醚萜类化合物的浓度。单独测试的橄榄苦苷、油橄榄苦素、油橄榄素、羟基酪醇和酪醇均降低了DPP-IV活性，其半数抑制浓度（IC）分别为472.3±21.7μM、187±11.4μM、354.5±12.7μM、741.6±35.7μM和1112±55.6μM。最后，通过计算机辅助分子对接模拟研究了这些化合物的结合模式。