Evodiamine Inhibits Zymosan-Induced Inflammation In Vitro and In Vivo: Inactivation of NF-κB by Inhibiting IκBα Phosphorylation.

Abstract

Evodiamine (EVO), an important alkaloidal component extracted from the fruit of Evodiae fructus, has been known to possess anti-tumor, anti-inflammatory, anti-oxidative, and other therapeutic capabilities. In the present study, the effects of EVO on zymosan-induced inflammation and its underlying mechanism were investigated both in vitro and in vivo. Our results showed that EVO effectively suppressed both protein and mRNA expression of interleukin-1β, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in vitro. Zymosan-induced DNA-binding activity of nuclear factor-kappa B (NF-κB) was attenuated by EVO, which was achieved through inhibitory effects on the phosphorylation of inhibitory κB α and p65 nuclear translocation, but there was very little association with mitogen-activated protein kinase activation. In vivo, treatment with EVO markedly decreased TNF-α and IL-6 levels in plasma. EVO also repressed inflammatory cytokine expression and ameliorated the abnormal state in both lung and intestine tissues by inactivation of NF-κB. Furthermore, EVO significantly reduced the mortality caused by zymosan. In summary, these results suggested that EVO could effectively suppress inflammatory responses in vitro and in vivo, and may be a potential therapeutic agent against inflammatory disorders.