RESUMEN
This study is to screen the Chinese herbal compounds which could inhibit the production of Abeta 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 Abeta and beta-secretases or Abeta and gamma-secretases. Extracellular Abeta was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 micromol x L(-1)), separately. Then the compounds were selected which could inhibit extracellular Abeta and their best concentration ranges were decided, too. Furthermore, the cell viability and apoptosis rate, the level of intracellular Abeta, beta and gamma-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 Abeta; 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 micromol x L(-1), respectively. Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Abeta were more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of beta and gamma-secretases, with the maximum inhibiting rates of 78.2% and 80.3%, respectively. In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit the expression and secretion of Abeta, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the beta and gamma-secretase activities, respectively.