Extraction-driven structural modulation dictates the anti-diabetic potency of Notopterygium franchetii...

Extraction-driven structural modulation of polysaccharides from Notopterygium franchetii was investigated to identify the structural determinants of anti-diabetic activity. Hot-water extraction and mild-acid extraction yielded three homogeneous fractions, among which WNP-1 (82.4 kDa) and ANP-1 (4.3 kDa) showed distinct structure-function profiles. Methylation and 1D/2D NMR analyses indicated that WNP-1 contained a relatively rigid, high-molecular-weight network enriched in →4)-α-D-Glcp-(1 → and →2)-β-D-Galp-(1 → linkages, whereas ANP-1 possessed a flexible →4)-α-D-Glcp-(1 → backbone with →3)-β-D-Galp-(1 → branches. These structural differences led to divergent functional properties. WNP-1 exhibited superior shear-thinning behavior and thermal stability, while ANP-1 showed the strongest α-glucosidase inhibition (IC₅₀ = 0.48 mg/mL). In diabetic mice, ANP-1 reduced fasting blood glucose by 23.79%, improved serum lipid profiles, alleviated liver injury, and decreased insulin resistance. In insulin-resistant HepG2 cells, ANP-1 enhanced glucose uptake and glycogen synthesis, accompanied by activation of IRS1/PI3K/AKT signaling. These results indicate that low molecular weight and enrichment of (1 → 3)-linked galactose residues are key structural features associated with enhanced anti-diabetic activity, whereas high molecular weight favors rheological and thermal performance.