Anti-inflammatory effects of egg white combined with chalcanthite in lipopolysaccharide-stimulated BV2 microglia through the inhibition of NF-κB, MAPK and PI3K/Akt signaling pathways

Egg white-chalcanthite (EWCC) is a mixture of egg white and chalcanthite prepared by roasting chalcanthite (which is a natural mineral mainly composed of CuSO4 center dot 5H(2)O) to the point of dehydration, pulverizing the dehydrated chalcanthite and then mixing the pulverized chalcanthite to react with egg white to trigger a reaction. When egg white-chalcanthite is prepared in this manner, the toxicity of chalcanthite is neutralized by the egg white, so that the toxicity is reduced or removed and the pharmaceutical properties are increased. However, the cellular and molecular mechanisms underlying the pharmacological activity of EWCC remain poorly understood. In this study, we investigated the inhibitory effects of EWCC on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators in BV2 microglia. Our data indicated that the EWCC treatment significantly inhibited the excessive production of nitric oxide and prostaglandin E., in LPS-stimulated BV2 microglia in a concentration-dependent manner without causing cytotoxicity. It also attenuated the expression of inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines, including interleukin-1 beta and tumor necrosis factor-alpha. Moreover, EWCC exhibited anti-inflammatory properties by the suppression of nuclear factor-kappa B (NF-kappa B) activation by blocking I kappa B-alpha degradation, downregulation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Our results indicate that the inhibitory effects of EWCC on UPS-stimulated inflammatory mediator production in BV2 microglia are associated with the suppression of the NF-kappa B, MAPK and PI3K/Akt signaling pathways. These findings suggest that EWCC may offer a substantial therapeutic potential for the treatment of neurodegenerative diseases that are accompanied by microglial activation.