A high concentration of fatty acids induces TNF-α as well as NO release mediated by the P2X4 receptor, and the protective effects of puerarin in RAW264.7 cells

Circulating levels of free fatty acids (FFAs) are often found to be increased in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS). High plasma FFA levels may give rise to maladaptive macrophage activation and promote inflammatory responses, which has been proposed as a potential mechanism for the development of DM and MS. P2X4 receptor (P2X4R), a ligand-gated cation channel activated by extracellular adenosine triphosphate (ATP), plays a primary role in the regulation of inflammatory responses. Puerarin has been reported to possess potential anti-inflammatory activity. However, the anti-inflammatory activity of puerarin and the underlying molecular mechanisms in a setting of a high concentration of FFAs remain unknown. In this study, we found that a high concentration of FFAs increased the expression of P2X4R, cytosolic Ca