Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

Abstract

Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1β, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1β and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1β and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Keywords: LPS; Mangiferin; NLRP3; Nrf2.