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Publications (2)6.19 Total impact

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    ABSTRACT: Sparstolonin B (SsnB) is an isocoumarin compound isolated from the tubers of both Sparganium stoloniferum and Scirpus yagara. We previously demonstrated that SsnB blocked the Toll-like receptor (TLR) 2- and TLR4-triggered inflammatory signaling in macrophages by inhibiting the recruitment of MyD88 to the TIR domains of TLR2 and TLR4. The present study was designed to examine the effects of SsnB on vascular inflammatory responses in human umbilical vein endothelial cells (HUVECs) challenged by lipopolysaccharide (LPS, a TLR4 ligand). We found that SsnB dose-dependently attenuated the LPS-induced expression of interleukin (IL)-1β and monocyte chemoattractant protein 1 both at the transcription and translation levels in HUVEC. LPS-induced endothelial cell adhesion molecules, intercellular adhesion molecular-1 and vascular cell adhesion molecule-1 expressions were also reduced by treatment with SsnB. In addition, co-incubation with SsnB attenuated THP-1 monocyte adhesion to LPS-activated HUVECs. Furthermore, SsnB efficiently suppressed LPS-induced phosphorylation of extracellular -signal-regulated kinase (Erk1/2) and Akt in HUVECs. These findings show that SsnB can suppress endothelial cell inflammation, suggesting that SsnB might be suitable for development as a therapeutic agent for inflammatory cardiovascular disease.
    Archives of Pharmacal Research 04/2013; · 1.54 Impact Factor
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    ABSTRACT: Blockade of excessive Toll-like receptor (TLR) signaling is a therapeutic approach being actively pursued for many inflammatory diseases. Here we report a Chinese herb-derived compound, sparstolonin B (SsnB), which selectively blocks TLR2- and TLR4-mediated inflammatory signaling. SsnB was isolated from a Chinese herb, Spaganium stoloniferum; its structure was determined by NMR spectroscopy and x-ray crystallography. SsnB effectively inhibited inflammatory cytokine expression in mouse macrophages induced by lipopolysaccharide (LPS, a TLR4 ligand), Pam3CSK4 (a TLR1/TLR2 ligand), and Fsl-1 (a TLR2/TLR6 ligand) but not that by poly(I:C) (a TLR3 ligand) or ODN1668 (a TLR9 ligand). It suppressed LPS-induced cytokine secretion from macrophages and diminished phosphorylation of Erk1/2, p38a, IκBα, and JNK in these cells. In THP-1 cells expressing a chimeric receptor CD4-TLR4, which triggers constitutive NF-κB activation, SsnB effectively blunted the NF-κB activity. Co-immunoprecipitation showed that SsnB reduced the association of MyD88 with TLR4 and TLR2, but not that with TLR9, in HEK293T cells and THP-1 cells overexpressing MyD88 and TLRs. Furthermore, administration of SsnB suppressed splenocyte inflammatory cytokine expression in mice challenged with LPS. These results demonstrate that SsnB acts as a selective TLR2 and TLR4 antagonist by blocking the early intracellular events in the TLR2 and TLR4 signaling. Thus, SssB may serve as a promising lead for the development of selective TLR antagonistic agents for inflammatory diseases.
    Journal of Biological Chemistry 06/2011; 286(30):26470-9. · 4.65 Impact Factor