Sparstolonin B suppresses lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells

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 (HU-VECs) 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.

Protective effects of the active fraction from the tuber of Scirpus yagara in mouse endotoxin shock model

“…Previous phytochemical studies showed various phenol acids, cisstilbenoids, aromatic alkine and isocoumarin isolated from Scirpus yagara would be the effective constituents (Cui et al, 2012;Liang et al, 2013aLiang et al, , 2013b. In the present study, we identified the presence of eight major compounds (protocatechuic acid, vanillic acid, p-coumaric acid, ferulic acid, sciryagarol I, methyl-3,6-dihydroxy-2-[2-(2-hydroxyphenyl)-ethynyl] benzoate, SsnB and SanLeng diphenyllactone) in AF by HPLC analysis.…”

“…In the present study, we identified the presence of eight major compounds (protocatechuic acid, vanillic acid, p-coumaric acid, ferulic acid, sciryagarol I, methyl-3,6-dihydroxy-2-[2-(2-hydroxyphenyl)-ethynyl] benzoate, SsnB and SanLeng diphenyllactone) in AF by HPLC analysis. Among these, SsnB cannot only block monocyte/macrophage inflammatory responses mediated by TLR2 and TLR4, but also can attenuate inflammation in vascular endothelial cells (Liang et al, 2011(Liang et al, , 2013a(Liang et al, , 2013b. Ferulic acid inhibits LPS/IFN-γ-induced NF-κB activity which plays pivotal roles in the immediate-early stages of immune and inflammatory response (Ou et al, 2003).…”

“…2, eight compounds from AF have been revealed (Cui et al, 2012;Liang et al, 2013aLiang et al, , 2013b). Fig.…”

“…In addition, these constituents have demonstrated anti-inflammatory, anti-oxidant, anti-HIV and anticancer activity (Yang et al, 2005;Kong et al, 2009;Yang et al, 2010). Recently we have identified several compounds from the tubers, including methyl-3,6-dihydroxy-2-[2-(2-hydroxyphenyl)-ethynyl] benzoate, ferulic acid, sparstolonin B (SsnB), sciryagarol I, II, etc (Cui et al, 2012;Liang et al, 2013aLiang et al, , 2013b. Among these compounds, SsnB, a selective Toll-like receptor 2 (TLR2) and TLR4 antagonist, can selectively block TLR2-and TLR4-mediated inflammatory responses in primary mouse macrophages in vitro (Liang et al, 2011).…”

Total synthesis of Sparstolonin B, a potent anti-inflammatory agent

“…[1][2][3] TLRs play an essential part in the perception of microbes and shape the complex host responses that occur during infection. 4 However, the signalling initiated by TLRs is a double-edged sword since a prolonged and exaggerated response can cause tissue and organ damage.…”