Screening of 10 types of Chinese herbal compounds inhibiting Aβ and their possible related mechanism in vitro

This study is to screen the Chinese herbal compounds which could inhibit the production of Aβ and investigate the underlying mechanism.Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial.The cell models which used could overexpress Aβ and β-secretases or Aβ and γ-secretases.Extracellular Aβ was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 µmol·L^-1), separately.Then the compounds were selected which could inhibit extracellular Aβ and their best concentration ranges were decided, too.Furthermore, the cell viability and apoptosis rate, the level of intracellular Aβ, β and γ-secretases were determined after the cell models treated with different concentrations of selected compounds.The results showed that 4 of the 10 compounds could reduce the level of extracellular Aβ; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 µmol·L^-1, respectively.Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Aβwere more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of β and γ-secretases, with the maximum inhibiting rates of 78.2% and 80.3%,respectively.In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit theexpression and secretion of Aβ, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the β and γ-secretase activities, respectively.