Structure characteristics of a pectic polysaccharide from the leaves of Cornus officinalis Sieb. et Zucc. (Shanzhuyu) and its inhibition on hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents a highly aggressive malignancy with limited treatment options. While the traditional herb Cornus officinalis Sieb. et Zucc. ( C. officinalis , commonly called Asiatic dogwood or “Shanzhuyu” in Chinese) is known for its hepatoprotective properties, the structural features and anti-HCC potential of polysaccharides from its leaves remain largely unexplored. Therefore, we hypothesized that the leaf-derived polysaccharides with uncharacterized structure may exhibit anti-HCC activity. In this study, a homogeneous anti-HCC polysaccharide, designated PCL-2I ( Mw = 67.0 kDa), was isolated from C. officinalis leaves, and its structure was characterized by monosaccharide composition, methylation analysis, partial acid hydrolysis, and NMR spectra. PCL-2I is a pectic polysaccharide with a backbone repeating unit: →[6,3)-β-Glc p -(1 → 6)-α-Gal p -(1 → 6)-α-Gal p -(1] x → [4)-α-Gal p A-(1 → 4)-β-Gal p A-OMe-(1] y → [4)-α-Gal p A-(1 → 2,4)-α-Rha p -(1 → 4)-α-Gal p A-(1 → 2)-α-Rha p -(1] z →. Its branched side chains include →6)-α-Gal p -(1→, →3)-α-Ara f -(1→, →3,5)-α-Ara f -(1→, and →2)-α-Rha p -(1→, with substitutions at C-3 of the Glc residue and C-4 of Rha residue, respectively. PCL-2I suppressed HCC growth in vivo and induced apoptosis in vitro by targeting pyruvate kinase M2 (PKM2), thereby attenuating glycolysis and disrupting hypoxia-inducible factor-1α oncogenic signaling. These effects may be attributed to PCL-2I's high content of arabinose and galactose. This study provides a theoretical foundation for utilizing PCL 2I, a pectic polysaccharide from C. officinalis leaves, as a potential therapeutic agent against HCC by targeting PKM2.