Effect of Aloe-emodin on Aβ42 Aggregation and Cytotoxicity in Presence of Al3+ / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo study the inhibitory effect of aloe-emodin （AE） on aluminum ion （Al3+）-induced β-amyloid protein 42 （Aβ42） aggregation and its depolymerization on formed Aβ42-Al3+ aggregates in vitro， and to investigate the effect of AE on the cytotoxicity of Aβ42 aggregation in the presence of Al3+. MethodThe Aβ42 group， Aβ42+Al3+ group， Aβ42+AE group， Aβ42+Al3++AE group and the depolymerization test group were set up in the experiment. The aggregation fibrosis process， aggregation morphology， aggregation size and cytotoxicity of Aβ42 in each group were detected by thioflavin T （ThT） fluorescence assay， transmission electron microscopy （TEM）， dynamic light scattering （DLS） experiment and thiazolyl blue （MTT） cytotoxicity assay. ResultCompared with the Aβ42 group， Al3+ could promote Aβ42 aggregation， increase the fluorescence intensity of ThT by 124.48%， induce the aggregation of Aβ42 to form fiber bundles with larger particle size， and significantly reduce the cell viability of human neuroblastoma SH-SY5Y cells （P<0.01）， thus reducing the cell survival rate to 51.05%. AE not only inhibited Aβ42 aggregation， but also inhibited Al3+-induced Aβ42 aggregation in a concentration-dependent manner. Compared with the Aβ42+Al3+ group， high concentration of AE could reduce the ThT fluorescence intensity to 41.66%， and change the polypeptide aggregation pathway to form amorphous aggregates with small particle size. Besides， it significantly inhibited the cytotoxicity of Aβ42 induced by Al3+ （P<0.01）， and restored the cell survival rate to 84.87%. Further depolymerization was conducted， AE could depolymerize Aβ42-Al3+ aggregates to make the formed aggregates disappear and form some small-particle short fibers and amorphous structure aggregates with low toxicity. ConclusionAE can inhibit Aβ42 aggregation and cytotoxicity in the presence of Al3+， depolymerize the formed Aβ42-Al3+ aggregates and alleviate the cytotoxicity， thus laying the foundation for exploring the mechanism of AE in the treatment of Alzheimer's disease.