Abstract:
This study is to screen the Chinese herbal compounds which could inhibit the production of A
β 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 A
β and
β-secretases or A
β and
γ-secretases.Extracellular A
β 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 A
β and their best concentration ranges were decided, too.Furthermore, the cell viability and apoptosis rate, the level of intracellular A
β,
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 A
β; 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 A
βwere 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 A
β, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the
β and
γ-secretase activities, respectively.