Cryptotanshinone inhibits LPS-induced proinflammatory mediators via TLR4 and TAK1 signaling pathway |
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| Authors: | Li Xin Lian Li-Hua Bai Ting Wu Yan-Ling Wan Ying Xie Wen-Xue Jin Xuejun Nan Ji-Xing |
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| Affiliation: | aKey Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China |
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| Abstract: | 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. |
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| Keywords: | Abbreviations: COX-2, cyclooxygenase-2 DMSO, dimethyl sulfoxide D-GlaN, D-galactosamine IL-1, interleukin-1 IκB-α, inhibitory kappa B-α IKK, IκB kinase iNOS, inducible nitric oxide synthase IRAK, interleukin-1 receptor-associated kinase LPS, lipopolysaccharide LBP, lipopolysaccharide-binding protein MAPK, mitogen-activated protein kinases, MAPKKK, MAPK kinase kinase MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MyD88, myeloid differentiation primary response gene 88 L-NIL, L-N6-(1-Iminoethyl)lysine hydrochloride NF-κB, nuclear factor-κB NO, nitric oxide PGE2, prostaglandin E2 TAK1, TGF-beta activated kinase 1 TAB, TAK1-binding protein TIRAP, toll/IL-1 receptor domain containing adaptor protein TLR4, toll-like receptor 4 TNF-α, tumor necrosis factor-α TRAF6, TNF receptor associated factor 6 TRAM, TRIF-related adaptor molecule TRIF, toll/IL-1 receptor domain containing adaptor inducing interferon-β |
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