Polysaccharides from Tetrastigma Hemsleyanum Diels et Gilg attenuate LPS-induced acute lung injury by modulating TLR4/COX-2/NF-κB signaling pathway

Abstract

Tetrastigma Hemsleyanum Diels et Gilg (Sanyeqing, SYQ), a traditional herb native to China, has been widely used in the treatment of inflammatory diseases, febrile convulsions and dysentery. Previous studies have demonstrated the hypoglycemic, anti-inflammatory and anti-pyretic effects of polysaccharides from SYQ (SYQP). However, the role of SYQP in acute lung injury (ALI) remained unknown. Our present study aimed to explore the protective effects of SYQP in ALI and explained its underlying mechanism. In vivo, Balb/c mice were intragastrically administered with SYQP and dexamethasone (DXMS) for 14 days which were intratracheally instilled (IT) with LPS at the last day. In vitro, A549 cells were pretreated with SYQP, DXMS or TAK-242, following by LPS stimulation for 24 h. The histopathological results showed that SYQP remarkably alleviated pulmonary macrophage infiltration and myeloperoxidase (MPO) levels. Additionally, SYQP evidently suppressed wet/dry (W/D) ratio of lung and white blood cells (WBC) in bronchoalveolar lavage fluid (BALF). Moreover, SYQP markedly reduced TNF-α, IL-6, IL-1β and COX-2 levels both in vivo and in vitro. Meanwhile, SYQP significantly attenuated oxidative stress through upregulating the levels of SOD and GSH-Px and downregulating the expressions of MDA and LDH in vivo, which was confirmed by in vitro results that SYQP could increase SOD activity and decrease MDA and NO contents. Importantly, a decline in protein expressions of TLR4, COX-2, NF-κB p50, phospho-NF-κB p65 and phospho-IκB-α was detected in vivo and in vitro. Taken together, our results demonstrated that SYQP ameliorated LPS-induced ALI by alleviating inflammation and oxidative stress via attenuating TLR4/COX-2/NF-κB signaling pathway.