Sinapic Acid Attenuates the Neuroinflammatory Response by targeting AKT and MAPK in LPS-activated microglial models

Sinapic acid (SA) is a phenolic acid that is widely found in fruits and vegetables, which has various bioactivities, such as antidiabetic, anti-inflammatory, anticancer and anxiolytic functions. Overactivated microglial cells play a major role in the development of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The objective of this study was to investigate the effect and mechanism of sinapic acid in microglia-derived neuroinflammatory models. Our results demonstrated that SA inhibited production of the nitric oxide (NO) pro-inflammatory factor, induced nitric oxide synthase (iNOS), induced interleukin (IL)-6 and enhanced the release of IL-10 in a dose-dependent manner. Subsequently, a mechanistic study revealed that SA remarkably attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, administration of SA regulated the production of inflammation-related cytokines and inhibited the phosphorylation of MAPK cascades and Akt in the mouse cerebral cortex. These results suggested that SA may offer a possible treatment for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.