Isobavachalcone and bavachinin from Psoraleae Fructus modulate Aβ42 aggregation process through different mechanisms in vitro

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.