Department of Pharmacy, Faculty of Medicine, University of Niš, Dr Zoran Djindjic blvd. 81, 18000 Niš, Serbia.
LAQV/REQUIMTE, Departamento de Ciências Químicas, Laboratório de Bromatologia e Hidrologia, Faculdade de Farmácia-Universidade do Porto, 4050-313 Porto, Portugal.
Molecules. 2023 Jan 28;28(3):1286. doi: 10.3390/molecules28031286.
Blackcurrant berries ( L.) are of great interest for food scientists/technologists as a source of delphinidin-3-rutinoside (D3R). This is an uncommon phenolic compound in diets that unveils potent antiproliferative activity besides its colour. Other phenolic compounds, such as chlorogenic acid (CA) and epicatechin (EC), also known by their antiproliferative effects, are abundant in foods and beverages. To design smart food/supplements combinations containing blackcurrant and improved anticancer properties at the gastrointestinal level, there is the need for more data concerning the combined effects of those molecules. In this work, synergistic, additive, or antagonistic effects against gastric and intestinal cancers of D3R, CA, and EC were assessed in vitro. The antiproliferative activity of D3R, CA, and EC, alone and in binary combinations (D3R+CA, D3R+EC, and CA+EC) on NCI-N87 (gastric) and Caco-2 (intestinal) cells, was assessed following the Chou-Talalay theorem at equipotent contributions (i.e., (IC)/(IC)). D3R presented the strongest antiproliferative activity of the single molecules tested, with IC values of 24.9 µM and 102.5 µM on NCI-N87 and Caco-2 cells, respectively. The combinations D3R+CA and CA+EC were synergic against NCI-N87 until IC and IC, respectively, while D3R+EC shifted from slight antagonism to synergism at higher doses. On Caco-2 cells, antagonism at low doses and synergism at high doses was observed. Therefore, the synergisms observed on the gastric cancer model at low doses occurred on the colon model only at high doses. Data herein described is vital to the targeted smart design of foods and supplements, as it is foreseen that the same combination of phenolic compounds causes different interactions/effects depending on the dose and gastrointestinal compartment.
黑加仑浆果（L.）因其富含矢车菊素-3-芸香糖苷（D3R）而受到食品科学家/技术人员的广泛关注。D3R 是饮食中一种罕见的酚类化合物，除了具有颜色外，还具有很强的抗增殖活性。其他酚类化合物，如绿原酸（CA）和表儿茶素（EC），也因其具有抗增殖作用而在食品和饮料中大量存在。为了设计含有黑加仑的智能食品/补充剂组合，并在胃肠道水平上提高抗癌特性，需要更多关于这些分子联合作用的数据。在这项工作中，体外评估了 D3R、CA 和 EC 对胃和肠癌细胞的协同、相加或拮抗作用。根据等效贡献（即（IC）/（IC）），通过 Chou-Talalay 定理评估了 D3R、CA 和 EC 单独以及二元组合（D3R+CA、D3R+EC 和 CA+EC）对 NCI-N87（胃）和 Caco-2（肠）细胞的增殖活性。D3R 是测试的单个分子中具有最强抗增殖活性的分子，对 NCI-N87 和 Caco-2 细胞的 IC 值分别为 24.9 μM 和 102.5 μM。D3R+CA 和 CA+EC 组合对 NCI-N87 具有协同作用，直至分别达到 IC 和 IC，而 D3R+EC 在较高剂量时从轻微拮抗作用转变为协同作用。在 Caco-2 细胞上，观察到低剂量时拮抗作用，高剂量时协同作用。因此，在低剂量时观察到的胃癌模型中的协同作用仅在高剂量时在结肠模型中观察到。本文描述的数据对于靶向设计食品和补充剂至关重要，因为预计相同的酚类化合物组合会根据剂量和胃肠道部位产生不同的相互作用/效果。
