Structural characterization and inhibitory activity against silicosis of a bioactive polysaccharide from Farfarae Flos.

BACKGROUND

Silicosis is a progressive fibrotic lung disease marked by chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition. There is evidence that natural polysaccharides have the potential to attenuate the progression of silicosis. Farfarae Flos (FF), a traditional Chinese medicine, has been widely used to treat cough, asthma, and bronchitis. However, the potential effects of polysaccharides from FF on silicosis remain unknown.

OBJECTIVE

This study aimed to investigate the anti-silicosis effects and underlying mechanisms of the polysaccharide from FF, as well as to characterize the structure.

METHODS

A crude polysaccharide (FFP) was extracted from FF, and a homogeneous polysaccharide (FFP1) was purified from FFP by ultrafiltration. The effects of FFP against silicosis were evaluated using a silica-induced mouse model. The underlying mechanisms were explored through gut microbiota and metabolomics. The structural characteristics of FFP1 were identified using HPLC-UV, GPC-MALS-RI, ion chromatography, GC-MS, FT-IR and NMR. In addition, the anti-silicosis effects and potential mechanisms of FFP1 were further investigated in TGF-β1-induced epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transition (FMT) models in vitro.

RESULTS

In this study, FFP was found to alleviate silicosis-related pathology in mice, as evidenced by histological analysis, ELISA, and immunohistochemistry. Gut microbiota and metabolomic analyses indicated that FFP mitigates silicosis by modulating gut microbiota composition and regulating the levels of phenylalanine. Furthermore, FFP1, characterized as a linear inulin-type fructan (5.891 kDa), attenuates silicosis progression by inhibiting the TGF-β1/Smad signaling pathway to suppress EMT and FMT in vitro.

CONCLUSION

In conclusion, FFP exerts anti-silicosis effects in vivo by modulating gut microbiota and phenylalanine metabolism. Furthermore, FFP1, a purified inulin-type fructan, inhibits TGF-β1/Smad-mediated EMT and FMT in vitro. These findings highlight the gut-lung axis as a promising therapeutic target for silicosis prevention and treatment.