期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 355, 期 -, 页码 1-8出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2018.06.007
关键词
Dihydronortanshinone; Inflammation; LPS; Macrophage
资金
- Science and Technology Development Fund of Macau Special Administrative Region (FDCT) [078/2016/A2]
- Research Fund of University of Macau [MYRG2016-00043-ICMS-QRCM]
Inflammation is considered to be the common pathophysiological basis for a series of diseases. Documented data showed the anti-inflammatory effects of Salvia miltiorrhiza Bunge (Danshen), a traditional herb. The pharmacological activities of dihydronortanshinone (DNT), a tanshinone isolated from Danshen, remain unknown. In this study, the anti-inflammatory effects and underlying mechanisms of DNT were investigated with a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. DNT significantly suppressed LPS-induced inflammatory mediators such as nitrite oxide (NO), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS). LPS-induced reactive oxygen species (ROS) generation was inhibited by DNT, rotenone (Rot), thenoyltrifluoroacetone (TTFA), and antimycin A (AA). Furthermore, DNT inhibited LPS-induced NF-kappa Bp65 phosphorylation, nuclear translocation, as well as JNK1/2 and p38MAPK phosphorylation. In addition, DNT interrupted Toll-like receptor 4 (TLR4) dimerization and molecular docking results suggested that it was buried in the pocket of TLR4-MD2 complex. In conclusion, DNT inhibited LPS-induced inflammation mainly through NF-kappa B, mitochondrial ROS, and MAPK pathways possibly mediated by interfering LPS-TLR4-MD2 complex.
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