Safflower yellow attenuates learning and memory deficits in amyloid β-induced Alzheimer’s disease rats by inhibiting neuroglia cell activation and inflammatory signaling pathways

Safflower yellow (SY) is an aqueous extract of natural safflower. Our laboratory has reported protective effects of alleviating memory impairment with SY in a transgentic mouse model of Alzheimer’s disease. The possible beneficial effects of SY on amyloid-β-induced neuroinflammation in dementia remain unclarified. This study we hypothesize that astrocytes and microglia may cause amyloid-β deposition and produce a neuroinflammatory response, aims to explain the role and mechanism of SY in regulating glial activation and reducing Aβ deposition in Aβ_1–42 induced rat model. Wistar rats were treated with SY for one month after bilateral hippocampal injection of aggregated Aβ_1–42; behavioral tests were performed to demonstrate the amelioration of cognitive function. After that, the contents of iNOS, IL-1β, IL-6, and TNF-α in AD brain was detected. Western blot and real-time PCR were used to detect the M1 and M2-associated markers to demonstrate the activation of microglia. The conducted experiments have revealed that SY could strengthen spatial learning and memory ability of dementia rats, decrease the contents of iNOS, IL-1β, IL-6, and TNF-α and depress the activation of glial cells. Moreover, the SY treatment inhibited the M1 release of pro-inflammatory cytokines (iNOS and CD86), increased the expression of arginase-1, CD206, and YM-1 thereby reduced inflammation in model rats. Thus our results indicated that SY has very important theoretical and clinical value for the research and development of Chinese medicine for the treatment of AD.