Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury.

Abstract

The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.