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 LPS­induced production of several inflammatory mediators in the bronchoalveolar lavage fluid (BALF), which included the chemotatic factors, granulocyte colony­stimulating factor, monocyte inflammatory protein­1α and B­lymphocyte colony inflammatory cytokines, including interleukin (IL)­1ß, IL­6, IL­12p40 and tumor necrosis factor­α, in a dose­dependent manner. In addition, the expression of the Toll­like receptor 4 (TLR4)/myeloid differentiation factor­2 (MD­2) compound, the phosphorylation of p38 mitogen­activated protein kinase (p38MAPK), c­Jun N­terminal kinase (JNK) and nuclear transcription factor­κB (NF­κB), in addition to the DNA binding activity of NF­κB p65 in lung tissues, were all attenuated following RTF treatment. However, RTF treatment had no effect on extracellular signal­regulated kinase (ERK). In conclusion, RTFs contributed to the regulation of LPS­induced ALI through the TLR4/MD-2-mediated NF­κB, JNK and p38MAPK pathways. This may be a potential therapeutic option for the treatment of inflammatory diseases.