Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5833742 | International Immunopharmacology | 2011 | 6 Pages |
Cryptotanshinone (CTN), one of the major constituents of tanshinones, was investigated for anti-inflammatory activity in the murine macrophage cell line RAW 264.7. CTN inhibited the production of nitric oxide (NO) production, as well as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages. Since CTN was considered as inhibiting LPS-triggered phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation, we consequently evaluated the expression of toll-like receptor 4 (TLR4) and CD14, as well as phosphorylation of TGF-β-activated kinase 1 (TAK1). CTN reduced the expression of CD14 and TLR4, and suppressed LPS-induced phosphorylation of TAK1. Furthermore, CTN significantly increased the survival rate against LPS challenge in D-galactosamine-sensitized mice, which was in line with in vitro results. These results suggested that CD14/TLR4 and TAK1 might be the potential molecular targets for addressing the protective effects of CTN on LPS-induced inflammatory effects in macrophages.
Graphical abstractDownload full-size imageHighlights⺠We focused on the anti-inflammatory activity of cryptotanshinone. ⺠Cyptotanshinone inhibited NO production, as well as expression of iNOS and COX-2. ⺠Cryptotanshinone downregulated the increased CD14/TLR4 by LPS. ⺠Cryptotanshinone suppressed LPS-induced phosphorylation of TAK1.