3.5 Compound 270 alleviates the excessive biosynthesis of inflammatory cytokines induced by intraperitoneal injection of LPS in C57BL/6J mice
Our observations had demonstrated that the anti-inflammation activity of 270 on LPS- induced macrophages in vitro. Subsequently, we further evaluated the plausible effect of 270 in vivo. LPS, the main pathogenic factor of sepsis, activates a cascade of inflammatory response, which could result in damage to organs. LPS is the pivotal stimulus for the massive production of various inflammatory mediators, which has widely been applied to establish sepsis-associated AKI and ALI mice models (Ju et al. , 2018; Islam et al. , 2019). So we determined the effect of oral administration with 270 on mice injected intraperitoneally with LPS (10 mg/kg) for 24 h. The effect of pretreatment with 270 on food take and body weight was firstly determined, there were no obvious differences among the various groups (Figure 5A). Whereas, the kidney index of mice in the LPS group was significantly higher than that in the Veh group, and pretreatment with 270 markedly relieved the kidney index of LPS-induced mice, and no distinct changes were discovered in the liver and lung index among the various groups (Figure 5B). The plasma levels of TNF-α, IL-1β, IL-6 and MCP 1 were dramatically elevated after intraperitoneal injection of LPS, and these alterations of pro-inflammatory cytokines following LPS challenge were remarkably ameliorated by administration with 270 (Figure 5C). Our findings reflected that 270 have anti-inflammation activity in vivo and may exert direct effect on kidney in LPS-induced mice.