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-Glcp-(1 → 6)-α-Galp-(1 → 6)-α-Galp-(1]_x → [4)-α-GalpA-(1 → 4)-β-GalpA-OMe-(1]_y → [4)-α-GalpA-(1 → 2,4)-α-Rhap-(1 → 4)-α-GalpA-(1 → 2)-α-Rhap-(1]_z→. Its branched side chains include →6)-α-Galp-(1→, →3)-α-Araf-(1→, →3,5)-α-Araf-(1→, and →2)-α-Rhap-(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 PCL2I, a pectic polysaccharide from C. officinalis leaves, as a potential therapeutic agent against HCC by targeting PKM2.