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  • Title: Tanshinone IIA inhibits lipopolysaccharide‑induced inflammatory responses through the TLR4/TAK1/NF‑κB signaling pathway in vascular smooth muscle cells.
    Author: Meng Z, Si CY, Teng S, Yu XH, Li HY.
    Journal: Int J Mol Med; 2019 Apr; 43(4):1847-1858. PubMed ID: 30816448.
    Abstract:
    To aim of the present study was to determine whether Tanshinone IIA (Tan IIA) inhibits lipopolysaccharide (LPS)‑induced inflammation in vascular smooth muscle cells (VSMCs) from rats and elucidate the underlying molecular mechanism. VSMCs were primarily cultured and then treated with LPS (1 µg/l) and Tan IIA (25, 50 and 100 µmol/l) for 24 h. Monocyte chemoattractant protein (MCP)‑1, interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α levels were detected by ELISA and reverse transcription‑quantitative polymerase chain reaction. Nitric oxide (NO) production was measured using the Griess reaction. The expression of Toll‑like receptor 4 (TLR4), nuclear factor (NF)‑κB (p65), and inducible NO synthase (iNOS), and the phosphorylation of transforming growth factor‑β‑activated kinase 1 (TAK1) were detected by western blot analysis. Tan IIA inhibited the LPS‑induced expression of MCP‑1, IL‑6, and TNF‑α in a concentration‑dependent manner and inhibited iNOS‑mediated NO production. In addition, Tan IIA suppressed the expression of TLR4, the phosphorylation of TAK1, and the nuclear translocation of NF‑κB (p65). The anti‑TLR4 antibody and TAK1 inhibitor 5Z‑7‑oxozeaenol partially attenuated the LPS‑induced expression of proinflammatory cytokines. In conclusion, Tan IIA inhibits LPS‑induced inflammatory responses in VSMCs in vitro through the partial suppression of the TLR4/TAK1/NF‑κB signaling pathway.
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