Abstract
Polymeric phenolic compounds often have limited bioavailability. Depolymerization can overcome this limitation and enhance their bioactivity. Red pine bark is rich in tannins and other phenolic compounds, making it a suitable candidate for functional enhancement via hydrogenolytic depolymerization. This study compared the potential of red pine bark extract and its hydrogenolytically depolymerized form to mitigate scopolamine (SCOP)-induced amnesia in rats using behavioral tests (Y-maze, passive avoidance, and Morris water maze). We also assessed long-term potentiation (LTP) in hippocampal slices and oxidative stress in PC-12 cells. Both extracts effectively improved SCOP-induced cognitive decline and reduced oxidative stress. Notably, depolymerized red pine bark extract demonstrated stronger rescue of SCOP-induced LTP suppression through muscarinic receptor-dependent mechanisms. Both extracts similarly alleviated N-methyl-D-aspartate receptor-dependent LTP impairment and exhibited no effect under α-amino-3-hydroxy-5-methyl-4-isoxyzolepropionic acid receptor blockade. These findings indicate that hydrogenolytic depolymerization enhances phenolic bioactivity and selectively protects synaptic plasticity relevant to cognitive function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-026-02092-1.