Abstract:Objective This study aimed to investigate the effects of different drying methods on the physicochemical quality and functional properties of Gastrodia elata (G.elata) and to elucidate the molecular mechanisms underlying the inhibition of acetylcholinesterase (AChE) by the active components of G. elata. Method G. elata samples were processed by hot air drying (HAD), vacuum freeze drying (FD), vacuum drying (VD), far-infrared drying (FIRD), and vacuum freeze-hot air combined drying. The variations in the physicochemical quality of G. elata were systematically evaluated. The components responsible for AChE inhibition were screened Overcoming the limitations of single method drying, the FD12-HAD3 combined drying process significantly promoted the conversion of parishins into gastrodin and p-hydroxybenzyl alcohol, increasing the mass fraction of the two compounds by 8.19% compared with the vacuum freeze drying group. The AChE inhibition rate of G. elata processed with the combined drying process reached 60.84%, which was significantly higher than those in other drying groups. The molecular dynamics simulations revealed that small molecules (p-hydroxybenzyl alcohol and gastrodin) precisely anchored the catalytic active site of AChE, while macromolecules (parishins) sterically blocked the peripheral anionic site, thereby establishing a network of multi-target synergistic competitive inhibition. Conclusion The FD12-HAD3 combined drying process exhibits outstanding efficacy in both enriching active components and enhancing AChE-inhibitory functions, providing a robust scientific basis for the high-quality processing of G. elata.