Backgroud: Hydroxysafflor yellow A (HSYA) has a certain improvement effect on Alzheimer's disease (AD) rats, but its specific mechanism is still unclear. The purpose of this study was to observe the regulatory effect of HSYA on learning and memory ability of AD rats induced by Aβ1-42.Materials and methods: Morris water maze test was used to evaluate the effect of HSYA on the learning and memory ability of AD model rats. To explore the effective targets and potential molecular mechanisms of HSYA in AD treatment based on quantitative proteomics.Results: Through the Morris water maze experiment, we found that after HSYA treatment, the learning ability of rats in the model group has been significantly improved. Quantitative proteomics results showed that among the 11 common differential proteins between the "model/sham operation" comparison group and the "HSYA treatment/model" comparison group, the cholesterol synthesis rate-limiting enzyme mevalonate decarboxylase (Mvd) Western Blot results are consistent with the results of quantitative proteomics analysis. We found that HSYA can inhibit the expression of BACE protein in hippocampus of AD rats and decrease the level of Aβ1-42. Besides, HSYA could also reduce cholesterol levels in serum and hippocampus.Conclusion: In summary, HSYA can effectively improve learning and memory disorders in AD rats, and exert neuroprotective effects by effectively controlling serum and brain cholesterol to down-regulate the expression of BACE and thus reduce the content of Aβ1-42.
Keywords: Alzheimer’s disease; Aβ; Hydroxysafflor yellow A; TMT; cholesterol.