Wang_2019_Int.J.Mol.Med_43_956

Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including antiapoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In lglutamatedamaged HT22 cells, 3h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase3 and increased the expression levels of Bcell lymphomaextra large, phosphorylated (P) protein kinase B and Pmammalian target of rapamycin compared with untreated cells. In mice with AD induced by dgalactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Abeta142 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Abeta142 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stressassociated apoptosis signaling pathway.