Echinacea polysaccharide alleviates LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of the TLR4/NF-κB signal pathway

Abstract

Lung injury is a common critical life-threatening syndrome. Inflammation is a key factor in the pathogenesis of lung injury. It is reported that Echinacea Polysaccharides (EP) has anti-inflammatory activity. However, the effect of EP on lung injury remains unclear. In our study, murine model of lung injury was induced with 2.5 mg/kg LPS before administration of 5 mg/kg or 10 mg/kg EP. EP ameliorated LPS-induced lung pathological damage, along with reduction in lung wet/dry weight ratio and myeloperoxidase activity. EP decreased the number of leukocytes, eosinophils, neutrophils, lymphocytes and macrophages in bronchoalveolar lavage fluid, and the release of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-treated lung. EP suppressed LPS-induced apoptosis along with down-regulation of Bcl2-associated X (Bax) and cleaved caspase-3 (CC3), and elevated B-cell lymphoma-2 (Bcl-2). Besides, RAW 264.7 cells were treated with EP 100 μg/ml for 1 h and then incubated with 1 μg/ml LPS for 24 h. TNF-α, IL-6 and IL-1β levels were lowered by treatment of EP in LPS-treated RAW 264.7 cells. Moreover, EP down-regulated the expression of toll-like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), p-IκBα, nuclear factor kappa-B (NF-κB), p-NF-κB, and up-regulated the inhibitor of NF-κB (IκBα) in vivo and in vitro following LPS induction, which is consistent with the effect of TAK-242. In conclusion, EP may alleviate LPS-induced lung injury via inhibiting inflammation, apoptosis and activation of TLR4/NF-κB signal pathway.

Keywords: Acute lung injury; Apoptosis; Echinacea Polysaccharide; Inflammation; Lipopolysaccharide; Toll-like receptor 4/NF-kappaB pathway.