ReferenceID 3356
Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway
Cell Death Dis
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-inflamma
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Record Fields
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- Reference Id
- 3356
- Evidence Id
- 19946
- Core Evidence Id
- 19946
- Source Reference Id
- 3
- Herb2 Reference Id
- HBREF000006
- Subject Paper Key
- HERB001193_28817116
- Pubmed Id
- 28817116
- Doi
- 10.1038/cddis.2017.389
- Paper Title
- Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway
- Paper 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-α, IL-6, and IL-1β in RAW264.7 cells, bone marrow-derived macrophages, and THP-1 cells. TTN attenuated the LPS-induced transcriptional activity of NF-κB and decreased IκB-α and IKK phosphorylation and NF-κB/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-κB/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.
- Journal
- Cell Death Dis
- Publish Year
- 2017
- Experiment Subject
- mouse; bone marrow-derived macrophages; raw264.7 cells; thp-1 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Inflammatory Disorders
- Paper Title Cn
- Paper Title En
- Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway
- Bilingual Status
- semi_complete