ABSTRACT
A bioactive chemical constituent, doliroside A, from Chinese traditional herbal medicine Dolichos falcata Klein was isolated, purified and identified by 60% ethanol extraction, thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy. Molecular interaction mechanism between doliroside and amyloid ß42 protein was evaluated by thioflavin T fluorescence (ThT), circular dichroism (CD), atomic force microscope (AFM), and differential scanning calorimeter (DSC) from the aspects of kinetics, secondary structure, morphology, and thermodynamics, respectively. Results show that the purity of doliroside A is 99.9% by HPLC, and its chemical structure is identified by 1H- and 13C-NMR. Doliroside A is observed to be concentration-dependent inhibiting the fibrillation of Aß42 with the IC50 value of 26.57 ± 1.6 µM. CD and DSC results imply that doliroside A can bind to the nuclei and oligomers of Aß42 to form a stable complex and suppress Aß42 fibrillation. AFM images show that doliroside A, after bound to the nuclei and oligomers, redirect Aß42 into off-pathway, amorphous oligomers. These findings not only provide a full insight into the molecular interaction mechanisms between Aß42 and doliroside A, but also facilitate the development of new native anti-AD drug of doliroside A compound.