Chinese herb, Sparganium stoloniferu-derived Sparstolonin B (SsnB) as an anti-inflammatory and anti-atherogenic agent

Principal Investigator: Daping Fan

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daping fan
Project PI: Daping Fan

The global aim of our research is to promote the regression of atherosclerotic plaques through restoring macrophage cholesterol homeostasis and controlling macrophage inflammation. The goal of the current study is to expand on our preliminary results that 1) SsnB has potent anti-inflammatory effects on macrophages by blocking Toll-like receptor 2 (TLR2) and TLR4 signaling; 2) SsnB diminishes the ability of activated endothelial cells to attract monocyte for adhesion and decreases arterial smooth muscle cell migration; 3) SsnB effectively suppresses inflammatory response in mice. We will test the hypothesis that SsnB can be developed as an anti-atherosclerosis agent by virtue of its selective inhibitory effects on TLR2 and TLR4 signaling. To test this hypothesis, we propose three specific aims. SA1. To elucidate the molecular mechanism by which SsnB blocks TLR2 and TLR4 signaling. We will express and purify the Toll/IL-1 receptor (TIR) domains of TLRs, the adaptor proteins TIRAP/Mal and MyD88, and examine the binding of SsnB to these proteins. SA2. To examine the effects of SsnB on resident vascular cells. We will test the hypothesis that SsnB suppresses the inflammatory phenotype in arterial endothelial and smooth muscle cells by blocking TLR2 and TLR4 signaling. SA3. To test the hypothesis that SsnB attenuates atherogenesis in mice. LDL receptor (LDLR) deficient mice will be fed high fat diet to induce hypercholesterolemia and atherosclerosis. SsnB will be administrated to test if it attenuates atherogenesis in these mice.

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