%0 Journal Article
%T Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway
%A Chunming Wang
%A Hongwei Gao
%A Naixin Kang
%A Qiong-ming Xu
%A Shilin Yang
%A Wen Sun
%A Xin Liu
%A Xiuping Chen
%A Yanli Liu
%J Archive of "Cell Death & Disease".
%D 2017
%R 10.1038/cddis.2017.389
%X Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-汐, IL-6, and IL-1汕 in RAW264.7 cells, bone marrow-derived macrophages, and THP-1 cells. TTN attenuated the LPS-induced transcriptional activity of NF-百B and decreased I百B-汐 and IKK phosphorylation and NF-百B/p65 nuclear translocation. Furthermore, TTN inhibited the LPS-induced transcriptional activity of AP-1, which was induced by the reduction of JNK1/2, ERK1/2, and p38MAPK phosphorylation. TTN blocked LPS-induced Toll-like receptor 4 (TLR4) dimerization, which consequently decreased MyD88 recruitment and TAK1 phosphorylation. In addition, TTN pretreatment effectively inhibited xylene-induced ear edema and LPS-induced septic death and improved LPS-induced acute kidney injury in mice. TTN exerts anti-inflammatory effects in vitro and in vivo by blocking TLR4 dimerization to activate MyD88每TAK1每NF-百B/MAPK signaling cascades, which provide the molecular basis of the anti-inflammatory effect of Danshen and suggest that TTN is a potential agent for the treatment of inflammatory diseases
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596575/