Erlejman Alejandra G, Fraga Cesar G, Oteiza Patricia I
IQUIFIB-Department of Biological Chemistry (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Free Radic Biol Med. 2006 Oct 15;41(8):1247-56. doi: 10.1016/j.freeradbiomed.2006.07.002. Epub 2006 Jul 11.
Procyanidins can exert cytoprotective, anti-inflammatory, and anticarcinogenic actions in the gastrointestinal tract. Previous evidence has shown that procyanidins can interact with synthetic membranes and protect them from oxidation and disruption. Thus, in this study we investigated the capacity of a hexameric procyanidin fraction (Hex) isolated from cocoa to protect Caco-2 cells from deoxycholic (DOC)-induced cytotoxicity, cell oxidant increase, and loss of monolayer integrity. Hex interacted with the cell membranes without affecting their integrity, as evidenced by a Hex-mediated increase in the transepithelial electrical resistance, and inhibition of DOC-induced cytotoxicity. DOC induced an increase in cell oxidants, alterations in the paracellular transport, and redistribution of the protein ZO-1 from cell-cell contacts into the cytoplasm. Hex partially inhibited all these events at concentrations ranging from 2.5 to 20 microM. Similarly, Hex (5-10 microM) inhibited the increase in cell oxidants, and the loss of integrity of polarized Caco-2 cell monolayers induced by a lipophilic oxidant (2,2'-azobis (2,4-dimethylvaleronitrile). Results show that the assayed procyanidin fraction can interact with cell membranes and protect Caco-2 cells from DOC-induced cytotoxicity, oxidant generation, and loss of monolayer integrity. At the gastrointestinal tract, large procyanidins may exert beneficial effects in pathologies such us inflammatory diseases, alterations in intestinal barrier permeability, and cancer.
原花青素可在胃肠道发挥细胞保护、抗炎和抗癌作用。先前的证据表明，原花青素可与合成膜相互作用并保护其免受氧化和破坏。因此，在本研究中，我们研究了从可可中分离出的六聚体原花青素组分（Hex）保护Caco-2细胞免受脱氧胆酸（DOC）诱导的细胞毒性、细胞氧化剂增加和单层完整性丧失的能力。Hex与细胞膜相互作用而不影响其完整性，这通过Hex介导的跨上皮电阻增加以及对DOC诱导的细胞毒性的抑制得以证明。DOC诱导细胞氧化剂增加、细胞旁转运改变以及蛋白质ZO-1从细胞间接触部位重新分布到细胞质中。Hex在2.5至20微摩尔的浓度范围内部分抑制了所有这些事件。同样，Hex（5 - 10微摩尔）抑制了细胞氧化剂的增加以及由亲脂性氧化剂（2,2'-偶氮双（2,4-二甲基戊腈）诱导的极化Caco-2细胞单层完整性的丧失。结果表明，所检测的原花青素组分可与细胞膜相互作用，并保护Caco-2细胞免受DOC诱导的细胞毒性、氧化剂生成和单层完整性丧失。在胃肠道中，大分子原花青素可能在诸如炎症性疾病、肠道屏障通透性改变和癌症等病理状况中发挥有益作用。
