Structural characterization of an active polysaccharide from Gardenia jasminoide and its anti-pulmonary fibrosis effect associated with TGF-β1/Smad3 signaling pathway.

Pulmonary fibrosis is a chronic fibrosing interstitial pneumonia leading to respiratory failure and even death. However, no effective therapy is available in clinical. Given the protective effect of geniposide from Gardenia jasminoides on pulmonary fibrosis, it was hypothesized that polysaccharides from this herb might exert consistent effects. Here, a novel polysaccharide (GP121) with a molecular weight of 77.5 kDa was isolated from Gardenia jasminoides. Unlike typical rhamnogalacturonan I (RG-I) type polysaccharide, its backbone is characterized as a mixture of the rhamnogalacturonan I (RG-I) and arabogalactan (AG) domain, both of which are linked by 1,6-glycosidic bond. The RG-I domain is predominantly branched at the O-4 by arabogalactan, while the AG domain is mainly branched at the O-3 by arabinose tetrasaccharide, and then by Gal sidechains of varying length. The in vitro experiments demonstrated that GP121 potently inhibited (>95 %) TGF-β1-induced abnormal proliferation in MRC-5 cells. Additionally, GP121 reduced abnormal cell migration by 37 % and also reversed the upregulated expression of type I collagen (COL1A1), vimentin, and α-smooth muscle actin (α-SMA) induced by TGF-β1. Moreover, the anti-pulmonary fibrosis effect of GP121 were synergistically enhanced by the Smad3 inhibitor SIS3. In conclusion, these findings demonstrate the potential of GP121 as a functional food for treating pulmonary fibrosis.