Sparstolonin B as a TLR antagonist in suppression of liver inflammation through epigenetic mechanisms

Principal Investigators Daping Fan and Saurabh Chatterjee

Daping Fan  Web Site 

Saurabh Chatterjee  Web Site

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In this project we will test the central hypothesis that Sparstolonin B (SsnB), a novel compound, isolated from Chinese herb, Sparganium stoloniferum, can halt the transition from simple hepatic steatosis to Non-alcoholic steatohepatitis (NASH) by virtue of its ability to inhibit TLR2 and TLR4 signaling in multiple liver cell types through epigenetic regulation. We will test our hypothesis using 3 mouse models of NASH: 1) Western diet fed apoE-/- mice administrated with one dose of LPS (LPS as a second hit, and a TLR-4 ligand); 2) A chronic environment-linked NASH model (A CYP2E1 substrate for oxidative stress as a second hit); and 3) A more established model by feeding wild type C57BL/6 mice with a methionine- and choline-deficient diet (MCD) which causes the transition from benign steatosis to steatohepatitis (Dietary interactions as a second hit). We will test epigenetic regulation of TLR-2, TLR-4 and MyD88 genes.

Recent Publications