Flavonoids from Radix Tetrastigmae improve LPS-induced acute lung injury via the TLR4/MD-2-mediated pathway

Total flavonoids isolated from Radix Tetrastigmae (RTFs) possess immunomodulatory activity, particularly on inflammation. In mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI), treatment with RTFs at 40, 80 and 160 mg/kg significantly reduced leukocyte infiltration, improved histopathological changes in lung tissues and decreased the LPS-induced production of several inflammatory mediators in the bronchoalveolar lavage fluid (BALF), which included the chemotatic factors, granulocyte colony-stimulating factor, monocyte inflammatory protein-1 alpha and B-lymphocyte colony inflammatory cytokines, including interleukin (IL)-1 beta, IL-6, IL-12p40 and tumor necrosis factor-alpha, in a dose-dependent manner. In addition, the expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) compound, the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK) and nuclear transcription factor-kappa B (NF-kappa B), in addition to the DNA binding activity of NF-kappa B p65 in lung tissues, were all attenuated following RTF treatment. However, RTF treatment had no effect on extracellular signal-regulated kinase (ERK). In conclusion, RTFs contributed to the regulation of LPS-induced ALI through the TLR4/MD-2-mediated NF-kappa B, JNK and p38MAPK pathways. This may be a potential therapeutic option for the treatment of inflammatory diseases.