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.
Highlights
IntroductionMacrophages, the immune cells against invading pathogens, have a cardinal role in innate immune response.[1,2] excessively activated macrophages usually cause the aberrant release of inflammatory mediators involved in diversified inflammatory diseases, such as rheumatoid arthritis, sepsis, and inflammatory bowel disease.[3,4,5] the inhibition of inflammatory mediators such as TNF-α, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and IL-6 is the priority in the development of new anti-inflammatory drugs
The inhibition of inflammatory mediators such as TNF-α, inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), IL-1β, and IL-6 is the priority in the development of new anti-inflammatory drugs
The lipophilic tanshinones were proposed to be the active components of Danshen
Summary
Macrophages, the immune cells against invading pathogens, have a cardinal role in innate immune response.[1,2] excessively activated macrophages usually cause the aberrant release of inflammatory mediators involved in diversified inflammatory diseases, such as rheumatoid arthritis, sepsis, and inflammatory bowel disease.[3,4,5] the inhibition of inflammatory mediators such as TNF-α, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and IL-6 is the priority in the development of new anti-inflammatory drugs.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
