A novel branched galacturonan from Gardenia jasminoides alleviates liver fibrosis linked to TLR4/NF-κB signaling

Gardenia jasminoides (GJ) is a classic edible medicine in China of which the fruit has been proved to alleviate liver damage. We hypothesized whether polysaccharide in the fruit could have comparable bioactivity. To address this, a novel polysaccharide GJE0.2-2, is purified from the fruit of Gardenia jasminoides. Indeed, GJE0.2-2 may attenuate CCl4-induced liver fibrosis in mice and impede the expression of critical fibrogenesis associated molecules such as alpha-SMA, FN1, and Collagen I induced by TGF-beta in human hepatic stellate LX-2 cells. Mechanism studies suggest that this bioactivity may be implicated in TLR4/NF-kappa B signaling pathway via directly binding to TLR4. The structure characterization shows that the backbone of this polysaccharide is mainly composed of galacturonic acid with minor rhamnose, branched with galactose and arabinose, galacturonic acid, and esterified hexenuronic acid (HexpA). These findings provide evidence for a novel pectin-linked polysaccharide-based new drug candidate development for liver fibrosis therapy.