药学研究2026，Vol.45Issue(8)：851-859,9.DOI:10.13506/j.cnki.jpr.2026.08.002
基于网络药理学和实验验证的不同炮制程度何首乌改善轻度认知障碍机制
Mechanism study on the improvement of mild cognitive impairment by different processing degrees of Polygonum multiflorum based on network pharmacology and experimental verification
摘要
Abstract
Objective To investigate the mechanisms by which Polygonum multiflorum Thunb.(PM),at different levels of processing,improves mild cognitive impairment,based on network pharmacology and animal experiments,thereby providing molecular evidence for the potentiation through processing' hypothesis.Methods Using network pharmacology and molecular docking methods,we screened for active components and targets associated with mild cognitive impairment(MCI),constructed a protein-protein interaction(PPI)network,and performed gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Molecular docking was performed on core constituents and key targets,and binding energies were calculated.Using a scopolamine-induced MCI mouse model,low-and high-dose groups were established for the crude product and the 'Process-3,P3','Process-6,P6' and'Process-9,P9' preparations,respectively.Mouse behavioural parameters,as well as indicators of oxidative stress,cholinergic activity,and central neurotransmitter levels in brain tissue,were assessed.Results Network pharmacology analysis revealed that PM exerts a multi-target,multi-pathway effect in improving MCI;Emodin methyl ether and emodin are likely to play a primary role,with Akt1 and PIK3CA identified as core targets,both exhibiting binding energies below-6.7 kcal·mol-1;The mechanism primarily involves the PI3K-Akt,HIF and FoxO signalling pathways.Results from animal experiments indicate that all treatment groups showed a significant reduction in error time and error frequency,along with a prolongation of latency.Furthermore,there were increases in GSH-Px,ChAT activity,GSH and ACh and GABA levels in brain tissue,whilst MDA levels,AChE activity and Glu levels were reduced.3.The expression levels of p-PI3K were significantly reduced in all treatment groups(P<0.05),whilst there were no statistically significant differences in p-Akt expression;Bcl-2 protein was up-regulated in the P3-L and P9 groups,whilst Bax was down-regulated in the high-dose raw product and P9 groups.Conclusion The improvement in MCI achieved by different preparation methods of PM is associated with enhanced antioxidant activity,regulation of the cholinergic system and balancing of central neurotransmitters,and can modulate the PI3K-Akt pathway;The P9-H preparation upregulates Bcl-2 and downregulates Bax,restoring the Bcl-2/Bax balance and inhibiting neuronal apoptosis,thereby elucidating the mechanism of synergistic enhancement through preparation at the molecular level.关键词
何首乌/炮制/轻度认知障碍/氧化应激/胆碱能系统/神经递质Key words
Polygonum multiflorum Thunb./Processing/Mild cognitive impairment/Oxidative stress/Cholinergic system/Neurotransmitters分类
医药卫生引用本文复制引用
王金泉,段云天,韦前同,曾春晖,杨柯..基于网络药理学和实验验证的不同炮制程度何首乌改善轻度认知障碍机制[J].药学研究,2026,45(8):851-859,9.基金项目
国家自然科学基金项目(No.82060718) （No.82060718）
国家中医药管理局"中药炮制传承技术传承基地"资助项目(No.JGY2021111) （No.JGY2021111）
广西自然科学基金项目(No.2023GXNSFDA026020) （No.2023GXNSFDA026020）
2024年广西中医药自筹经费科研课题(No.GXZYA20240281) （No.GXZYA20240281）
