Hydroxysafflor yellow A ameliorates lipopolysaccharide-induced acute lung injury in mice via modulating toll-like receptor 4 signaling pathways

Hydroxysafflor yellow A (HSYA) is a main bio-active compound important of a traditional Chinese medicine named Carthamus tinctorius L. and has been shown to possess various effects, especially anti-inflammatory benefits and potential protections against acute lung injury (ALI) in previous studies. Therefore, in this present study, we aimed to evaluating effects of HSYA on lipopolysaccharide (LPS)-induced ALI in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results demonstrated that HSYA abated LPS-induced pathological change and attenuated lung vascular permeability and edema. HSYA down-regulated both the ability of myeloperoxidase (MPO) in lung tissues and levels of inflammatory mediators including tumor necrosis factor (TNF)-alpha, interleukin (1)-1 beta, IL-6 and IFN(interferon)-beta in serum. Moreover, HSYA prevented toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-beta (TRIF) protein up-expressions. In addition, the activations of mitogen-activated protein kinases including p38, extracellular signal-regulated kinase (ERR), c-Jun N-terminal kinase (JNK) were blocked by HSYA. And also, the phosphorylations of interferon regulatory factor 3 (IRF3), translocation of nuclear factor kappa B (NF-kappa B)/p65 and inhibitory kappa B (I kappa B)-alpha were inhibited by HSYA. In conclusion, HSYA attenuated inflammatory response in AU mice through inhibition of TLR 4-dependent signaling pathways. (C) 2014 Elsevier B.V. All rights reserved.