[1] Association Z. 2024 Alzheimer’s disease facts and figures[J]. AlzheimersDement, 2024,20(5) : 3708-3821.
[2] 仇成轩 , 杜怡峰. 重视阿尔茨海默病和老年痴呆症的人群干预 研究[J]. 山东大学学报(医学版) , 2017, 55(10) : 1-6.
[3] Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention , intervention, and care: 2020 report of the Lancet Commission[J]. Lancet, 2020, 396(10248) : 413-446.
[4] 李腾飞 , 郭志全 , 王晔. β-淀粉样蛋白代谢异常与阿尔茨海默病 [J]. 神经疾病与精神卫生 , 2022, 22(12) : 904-908.
[5] LiS, WeiZ, Chen J, et al. Oral administration of a fusion protein between the cholera toxin B subunit and the 42-amino acidisoform of amyloid-βpeptide produced in silkworm pupae protects against Alzheimer’s disease in mice[J]. PLoS One, 2014, 9(12) : e113585.
[6] RocchiA, Yamamoto S, Ting T, et al. A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomersand improved cognition in Alzheimer’s disease[J]. PLoSGenetics, 2017, 13(8) : e1006962.
[7] Aboelwafa H R, El-kott A F, Abd-Ella E M, et al. The possible neuroprotective effect of silymarin against aluminum chloride -prompted Alzheimer’s-like disease in rats[J]. Brain Sciences, 2020, 10(9) : 628.
[8] ToboreT O. On the central role of mitochondria dysfunction and oxidative stress in Alzheimer’s disease[J]. Neurological Sciences, 2019, 40(8) : 1527-1540.
[9] Kawamoto EM, MunhozCD, GlezerI, etal. Oxidative state in platelets and erythrocytes in aging and Alzheimer’s disease [J]. NeurobiologyofAging, 2005, 26(6) : 857-864.
[10] Stancu IC, CremersN, VanrusseltH, etal. AggregatedTau activatesNLRP3-ASCinflammasomeexacerbating exogenously seeded and non-exogenously seeded Tau pathologyin vivo[J]. ActaNeuropathologica, 2019, 137(4) : 599-617.
[11] ConnollyK, Lehoux M, O’Rourke R, et al. Potential role of chitinase-3-likeprotein1 (CHI3L1/YKL-40) inneurodegeneration andAlzheimer’s disease[J]. Alzheimer’s & Dementia, 2023, 19 (1) : 9-24.
[12] 王刚 , 齐金蕾 , 刘馨雅 , 等. 中国阿尔茨海默病报告 2024[J]. 诊断学理论与实践 , 2024, 23(3) : 219-256.
[13] CummingsJ, LeeG, MortsdorfT, etal. Alzheimer’s disease drug development pipeline: 2017 [ J ]. Alzheimer’ s & Dementia : Translational Research & Clinical Interventions, 2017, 3(3) : 367-384.
[14] Silva T, ReisJ, TeixeiraJ, etal. Alzheimer’sdisease, enzyme targetsand drugdiscoverystruggles: From naturalproductsto drugprototypes[J]. AgeingResearchReviews, 2014, 15: 116- 145.
[15] LiuX Q, YiW J, XiBH, etal. Identification ofdrug-disease associations using a random walk with restart method and supervised learning[J]. Computational and Mathematical Methodsin Medicine, 2022, 2022: 7035634.
[16] Yu N, Huang Y, Jiang Y, et al. Ganoderma lucidum Triterpenoids ( GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer ’s Disease Mice[J]. Oxidative Medicine and Cellular Longevity, 2020, 2020(1) : 9894037.
[17] Bao M L, Bade R G, Liu H, et al. Astragaloside IV against Alzheimer’s disease via microglia-mediated neuroinflammation using network pharmacology and experimental validation[J]. EuropeanJournalofPharmacolo gy, 2023, 957: 175992.
[18] DartiguesJ F, Grasset L, Helmer C, et al. Ginkgo biloba extract consumption and long-term occurrence of death and dementia[J]. The Journal of Prevention of Alzheimer’s Disease, 2017, 4(1) : 16-20.
[19] SavaskanE, Mueller H, HoerrR, et al. Treatment effects of GinkgobilobaextractEGb761 onthespectrum ofbehavioraland psychologicalsymptoms ofdementia: Meta-analysis ofrandomized controlledtrials[J]. InternationalPsychogeriatrics, 2018, 30(3) : 285-293.
[20] 冯孝章 , 陈玉武 , 杨峻山. 天麻化学成分的研究[J]. 化学学 报 , 1979, 37(3) : 175-182.
[21] Menyiy N E, Elouafy Y, Moubachir R, et al. Chemistry, biological activities, and pharmacological properties of gastrodin : Mechanism insights. [J]. Chemistry& Biodiversity, 2024, 21(6) : e202400402.
[22] Yu H, Zang J, Chen B Q, et al. Research progress on classification ofchemicalconstituents from Gastrodia elata and theirpharmacological effects[J]. Chin Tradit Herbal Drugs, 2022, 53: 5553-5562.
[23] Tang C L, Wang L, Liu X X, et al. Comparative pharmacokinetics of gastrodin in rats after intragastric administration of free gastrodin, parishin and Gastrodia elata extract [J]. JournalofEthnopharmacology, 2015, 176: 49-54.
[24] Liu Y, Gao J L, PengM, etal. A review on centralnervous system effects of gastrodin[J]. Frontiers in Pharmacology, 2018, 9: 24.
[25] Zhao FY, Yin CL, LaiY F, etal. Extraction, purification, characteristics, bioactivities, application, and toxicity of GastrodiaR . Br. polysaccharides: A review[J]. International JournalofBiologicalMacromolecules, 2025, 301: 140084.
[26] Wang Y L, Bai M T, Wang X, et al. Gastrodin: A comprehensive pharmacological review [ J ]. Naunyn- Schmiedeberg ’s Archives of Pharmacology, 2024, 397(6) : 3781-3802.
[27] Liu CM, Tian Z K, Zhang Y J, et al. Effects of gastrodin againstlead-induced brain injury in mice associ ated with the Wnt /Nrf2pathway[J]. Nutrients, 2020, 12(6) : 1805.
[28] deOliveiraMR, BrasilFB, FürstenauCR. Nrf2mediatesthe anti-apoptotic and anti-inflammatory effects induced by gastrodin in hydrogen peroxide-treated SH-SY5Y cells[J]. JournalofMolecularNeuroscien ce, 2019, 69(1) : 115-122.
[29] ZhangJS, Zhou SF, Wang Q, et al. Gastrodin suppresses BACE 1 expression under oxidative stress condition via inhibition of the PKR/eIF2α pathway in Alzheimer’s disease [J]. Neuroscience, 2016, 325: 1-9.
[30] JiaoM, Yin K Z, Zhang T, et al. Effect of the SSeCKS- TRAF6interactionongastrodin-mediatedprotec tion against2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced astrocyte activation and neuronaldeath[J]. Chemosphere, 2019, 226: 678-686.
[31] Zhou L P, Chen X Y, Liang S , et al. Exploring gastrodin againstaging-related genesinAlzheimer’sdiseasebyintegrated bioinformaticsanalysisand machine learning[J]. International JournalofMolecularSciences , 2025, 26(18) : 9097.
[32] Zhu C H, Wang ST, Ma S Y, et al. Gastrodin reduces Aβ brain levels in an Alzheimer’s disease mouse model by inhibiting P-glycoprotein ubiquitination[J]. Phytomedicine, 2024, 135: 156229.
[33] Lei H P, Yang X, Hu Y T, et al. Gastrodin alleviates mitochondrial energy metabolism dysfunction via activatingβ- catenin /c-Myc/MCT2signaling in Alzheimer’s disease models [J]. Journalofethnopharmacology, 2026, 354:120548.
[34] Guo T, Zhang D, Zeng Y, et al. Molecular and cellular mechanismsunderlyingthepathogenesisofAlzheimer’sdisease [J]. MolecularNeurodegeneration, 2020, 15(1) :40.
[35] Sun Y Y, Wang Z, Huang H C. Roles ofAPOE4 on the pathogenesis in Alzheimer’ s disease and the potential therapeutic approaches [ J ]. Cellular and Molecular Neurobiology, 2023, 43(7) : 3115-3136.
[36] Vecchio F L, Bisceglia P, Imbimbo B P, et al. Are apolipoprotein E fragmentsa promising new therapeutictarget forAlzheimer ’s disease? [J]. Therapeutic advances in chronic disease, 2022, 13:20406223221081605.
[37] ChangSJ, MaT R, Miranda R D, etal. Lipid-and receptor- bindingregionsofapolipoproteinE4fragmentsactinconcertto cause mitochondrial dysfunction and neurotoxicity [ J ]. ProceedingsoftheNationalAcademyofSciencesoftheUnited StatesofAmerica , 2005, 102(51) : 18694-18699.
[38] HuangYD, MuckeL. Alzheimermechanismsand therapeutic strategies[J]. Cell , 2012, 148(6) : 1204-1222.
[39] LiangT, Hang W J, Chen J H, et al. ApoE4 (Δ272-299) induces mitochondrial-associated membrane formation and mitochondrial impairment by enhancing GRP75-modulated mitochondrial calcium overload in neuron [ J ]. Cell & Bioscience, 2021, 11(1) : 50.
[40] LiuJ, PeiT, MuJ,etal. SystemsPharmacologyUncoversthe Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever[J]. Evidence-Based Complementary and Alternative Medicine, 2016, 2016(1) : 9025036.
[41] Ran B, Chen L, Li M J, et al. Drug-drug interactions prediction using fingerprint only[ J]. Computational and MathematicalMethodsinMedicine, 2022, 2022(1) : 7818480.
[42] Pires M, Rego A C. Apoe4 and Alzheimer’s Disease Pathogenesis-Mitochondrial Deregulation and Targeted TherapeuticStrategies[J]. Internationaljournal of molecular sciences , 2023, 24(1) :778.
[43] Zhang H, Yuan B, Huang H, et al. Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation[J]. Brazilian Journal of Medical and BiologicalResearch, 2018, 51(10) : e7439.
[44] TonA M M, Campagnaro B P, Alves G A, et al. Oxidative Stress and Dementia in Alzheimer’s Patients: Effects of SynbioticSupplementation[J]. OxidativeMedicine and Cellular Longevity, 2020, 2020(1) : 2638703.
[45] Li Y, Zhang E, Yang H, et al. Gastrodin Ameliorates Cognitive Dysfunction in Vascular Dementia Rats by SuppressingFerroptosisviatheRegulation oftheNrf2/Keap1- GPx 4 SignalingPathway[J]. Molecules, 2022, 27(19) : 6311.
[46] Czabotar P E, Lessene G, Strasser A, et al. Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy[J] Nature Reviews Molecular Cell Biology, 2014, 15(1) : 49-63.
[47] 柳正 ,王朝晖. 蛋白质酪氨酸激酶2通过 PI3K/AKT/Gsk3b信 号调控 Tau磷酸化[J]. 标记免疫分析与临床 , 2022, 29 (3) : 464-470.
[48] Yao Y Y, Li R, Guo Y J, et al. Gastrodin attenuates lipopolysaccharide-induced inflammatory response and migration via the Notch-1 signaling pathway in activated microglia [J]. NeuroMolecular Medicine, 2022, 24(2) : 139- 154.
[49] BeurelE, Grieco SF, JopeR S. Glycogen synthase kinase-3 (GSK3) : Regulation, actions, and diseases[J]. Pharmacology & Therapeutics, 2015, 148:114-131.
[50] LuZ, Fu J, Wu G, etal. Neuroprotection and mechanism of gas -miR36-5pfrom Gastrodia elata in an Alzheimer’s disease model by regulating glycogen synthase kinase-3β [ J ]. InternationalJournal of Molecular Sciences, 2023, 24(24) : 17295.
[51] HernndezF, GmezdeBarredaE, Fuster-MatanzoA, etal. GSK 3: A possible link between beta amyloid peptide and tau protein[J]. ExperimentalNeurology, 2010, 223(2) :322-325.
[52] Engel T, Goñi-Oliver P, Lucas J J, et al. Chronic lithium administration to FTDP-17 tau and GSK-3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangleformation , butpre-formedneurofibrillarytanglesdo not revert [J]. Journal of Neurochemistry, 2006, 99(6) : 1445- 1455.