Inhibitory effects of magnolol and honokiol on human calcitonin aggregation.
Inhibitory effects of magnolol and honokiol on human calcitonin aggregation.
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厚朴酚和和厚朴酚对人降钙素聚集的抑制作用
DOI：
10.1038/srep13556
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发表时间：
2015-09-01
影响因子：
4.6
通讯作者：
Huang K
中科院分区：
文献类型：
--
作者：
Guo C;Ma L;Zhao Y;Peng A;Cheng B;Zhou Q;Zheng L;Huang K
淀粉样蛋白的形成与多种淀粉样变性疾病相关。人降钙素(hCT)是一种典型的淀粉样肽，其聚集与甲状腺髓样癌(MTC)相关，也限制了其临床应用。它的两种主要多酚成分厚朴酚（Mag）和和厚朴酚（Hon）具有多种功能。黄酮类化合物及其衍生物等多酚作为淀粉样蛋白抑制剂已被广泛研究。然而，含有多酚（例如 Mag 和 Hon）的联苯主链的抗淀粉样蛋白生成特性尚未见报道。在本研究中，测试了这两种化合物对 hCT 聚集的影响。我们发现Mag和Hon均抑制hCT淀粉样蛋白的形成，其中Mag表现出更强的抑制作用；此外，它们都以剂量依赖性方式分解预先形成的 hCT 聚集体。进一步的免疫点印迹和动态光散射研究表明，Mag 和 Hon 在寡聚和纤维化阶段均抑制了 hCT 的聚集，而基于 MTT 和染料渗漏分析表明，Mag 和 Hon 有效降低了 hCT 聚集体引起的细胞毒性。此外，等温滴定量热法表明 Mag 和 Hon 均与 hCT 相互作用。总之，我们的研究表明这两种化合物及其结构相关衍生物具有潜在的抗淀粉样蛋白生成特性。
Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC) and also limits its clinical application.Magnolia officinalisis a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.