A highly sulfated α-1,4-linked Galactoglucan of Antrodia cinnamomea with anti-inflammatory and anti-Cancer activities

Abstract

Sulfate polysaccharides (SPS) are polysaccharides with highly anionic properties due to of the binding of negatively charged sulfate groups to the central sugar backbone. This study aims to structurally elucidate and functionally evaluate a natural SPS purified from fraction 2 of SPS of 50 mM ammonium sulfate feeding of A. cinnamomea, noted as N50 F2. N50 F2 exhibited a high sulfate content of 3.89 mmol/g demonstrated excellent anti-cancer activity. Its anti-inflammatory effect is mediated by down-regulating AKT phosphorylation and reducing TGFRII expression in LPS-induced macrophage cells. The anti-cancer activity of N50 F2 is achieved through the down-regulation of the phosphorylation of AKT/ERK/EGFR/FAK and the inhibition of slug, TGFRI, and TGFRII's expression. N50 F2 also activated apoptotic related molecules of CHOP, and cleavage PARP, caspase 3 in lung cancer cells. Structural delineation demonstrated that N50 F2 was a sulfated α-1,4-linked galactoglucan, with a glucosyl branch on the 3-O position of one skeleton moiety and a galactosyl on the 6-O position of another, with sulfate substitutions on all the hydroxy positions. This study offers a reliable production method for SPS and highlights the potential of SPS for pharmaceutical applications.