Abstract

We previously demonstrated that coencapsulation of the potent antioxidant astaxanthin (Asx) and tocotrienols into liposomes results in synergistically higher antioxidative activity than the calculated additive activity of each individual antioxidant-containing liposome, due to intermolecular interactions between terminal ring moieties of the two antioxidants and the polyene chain and the triene moiety. We reported that intermolecular interactions depend on the stereochemistry of Asx, and change the electronic state of the Asx polyene moiety. Based on these findings, we hypothesised that antioxidants that interact with Asx at the terminal ring and polyene moieties may enhance the antioxidative activity. Herein, we selected two candidate antioxidants, capsaicin (Cap) and resveratrol, based on their structures, in which the compounds exhibit similar characteristics to tocotrienols. We evaluated the antioxidative capacities of liposomes coencapsulating Asx and the selected candidates. Based on hydroxyl radical scavenging activity, Cap was found to synergistically enhance the antioxidative activity of Asx at an optimal Asx/Cap ratio. Intermolecular interactions between Asx and Cap are necessary for the synergistic effect, and the Asx stereoisomer 3R,3′R-form (Asx-R) was predicted to most potently interact. Liposomes coencapsulating Asx-R and Cap exhibited clear synergistic antioxidative activity at an optimal ratio, whereas liposomes coencapsulating the other Asx stereoisomer and Cap did not demonstrate such activity. Computational chemistry analysis showed that changes in the electronic state of the polyene moiety of Asx-R are crucial for the synergistic activity. These results suggest that antioxidants that can change the electronic state of Asx via intermolecular interactions may enhance the function of Asx.

摘要

我们之前已经证明，由于两种抗氧化剂的末端环部分和生育三烯酚之间的分子间相互作用，将强效抗氧化剂虾青素 (Asx) 和生育三烯酚共包封到脂质体中会产生比每个含抗氧化剂脂质体的计算加成活性更高的协同抗氧化活性。多烯链和三烯部分。我们报道了分子间相互作用取决于 Asx 的立体化学，并改变 Asx 多烯部分的电子状态。基于这些发现，我们假设在末端环和多烯部分与 Asx 相互作用的抗氧化剂可能会增强抗氧化活性。在此，我们根据其结构选择了两种候选抗氧化剂，辣椒素 (Cap) 和白藜芦醇，其中化合物表现出与生育三烯酚相似的特性。我们评估了共封装 Asx 和所选候选物的脂质体的抗氧化能力。基于羟基自由基清除活性，发现 Cap 在最佳 Asx/Cap 比率下协同增强 Asx 的抗氧化活性。Asx 和 Cap 之间的分子间相互作用是协同效应所必需的，而 Asx 立体异构体 3R ,3' R型 (Asx- R ) 被预测为最有效的相互作用。共封装 Asx- R和 Cap 的脂质体在最佳比例下表现出明显的协同抗氧化活性，而共封装其他 Asx 立体异构体和 Cap 的脂质体没有表现出这种活性。计算化学分析表明，Asx- R多烯部分的电子态变化对于协同活性至关重要。这些结果表明，可以通过分子间相互作用改变 Asx 电子状态的抗氧化剂可能会增强 Asx 的功能。