State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
FEBS Lett. 2013 Sep 17;587(18):2930-5. doi: 10.1016/j.febslet.2013.07.037. Epub 2013 Jul 29.
Spontaneous aggregation of Aβ is a key factor in the development of Alzheimer's disease. In searching for Aβ aggregation inhibitors from traditional Chinese herbal medicines, we identified two active compounds from Psoraleae Fructus, namely isobavachalcone and bavachinin. We further demonstrated that the two compounds modulate Aβ42 aggregation process through different mechanisms. Isobavachalcone significantly inhibits both oligomerization and fibrillization of Aβ42, whereas bavachinin inhibits fibrillization and leads to off-pathway aggregation. Both of the compounds attenuated Aβ42-induced toxicity in a SH-SY5Y cell model. These findings may provide valuable information for new drug development and Alzheimer's therapy in the future.
β淀粉样蛋白的自发聚集是阿尔茨海默病发展的关键因素。在从传统中药中寻找β淀粉样蛋白聚集抑制剂的过程中，我们从补骨脂中鉴定出两种活性化合物，即异补骨脂查尔酮和补骨脂素。我们进一步证明，这两种化合物通过不同的机制调节β淀粉样蛋白 Aβ42 的聚集过程。异补骨脂查尔酮显著抑制 Aβ42 的寡聚化和纤维化，而补骨脂素抑制纤维化并导致偏离途径的聚集。这两种化合物都能减轻 Aβ42 在 SH-SY5Y 细胞模型中的毒性。这些发现可能为未来的新药开发和阿尔茨海默病治疗提供有价值的信息。
