Study On The Effects Of Active Ingredients Of Anti-Alzheimer’s Traditional Chinese Medicine On Aβ42 Aggregation And Cytotoxicity

Aim:Alzheimer’s disease(AD)is a neurodegenerative disease mainly caused by the accumulation of amyloid-β(Aβ)in the brain.More and more studies have confirmed that Traditional Chinese Medicine(TCM)has been used to treat AD and related cognitive impairment for centuries with obvious efficacy.Extracts or active ingredients of TCMs have been reported to inhibit the aggregation and cytotoxicity of Aβ.However,there is a lack of systematic research on the anti-Aβ aggregation effects of TCM components.This article aims to perform a systematic screening to identify the active ingredients of TCM against the cytotoxic aggregation of Aβ42.Methods:Through literature and database survey,we selected compounds that widely used in the treatment of AD with unknown anti-amyloid effects.Then,we used cytotoxicity test to screen out compounds which have less toxic and can inhibit the cytotoxicity of Aβ42.Finally,Thioflavin-T fluorescence detection,transmission electron microscopy,dynamic light scattering and dye leakage experiments were used to assess the in vitro inhibitory effect of the compounds on the aggregation and membrane rupture ability of Aβ42.Results:We selected 19 TCM herbals frequently used in the treatment of AD,from which 76 major active chemicals with unknown anti-amyloid effects were further screened.Through two rounds of cytotoxicity experiments,we screened the cytotoxicity of these chemicals and their effects on Aβ42-induced cytotoxicity.Tetrahydroxystilbene-2-O-β-D-glucoside(TSG)and sinapic acid(SA)were found to be less toxic,with inhibition of the cytotoxicity of Aβ42.Further studies demonstrated that TSG and SA concentration-dependently attenuated the amyloidosis and membrane disruption ability of Aβ42.Conclusions:We identified two novel chemicals(TSG and SA)against the cytotoxic aggregation of Aβ42.Innovation:Through systematic screening,we identified two novel chemicals(TSG and SA)against the cytotoxic aggregation of Aβ42,suggesting the potential of TSG and SA as candidate compounds for the treatment of AD.