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Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway.


ABSTRACT: 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-?, IL-6, and IL-1? in RAW264.7 cells, bone marrow-derived macrophages, and THP-1 cells. TTN attenuated the LPS-induced transcriptional activity of NF-?B and decreased I?B-? and IKK phosphorylation and NF-?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-TAK1-NF-?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.

SUBMITTER: Gao H 

PROVIDER: S-EPMC5596575 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway.

Gao Hongwei H   Liu Xin X   Sun Wen W   Kang Naixin N   Liu Yanli Y   Yang Shilin S   Xu Qiong-Ming QM   Wang Chunming C   Chen Xiuping X  

Cell death & disease 20170817 8


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 secret  ...[more]

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