天麻对神经退行性疾病的作用及其机制研究进展

doi:10.3969/j.issn.1674-490X.2025.04.001

摘要/Abstract

摘要： 天麻,作为中国传统名贵中药材,被广泛用于治疗头痛、眩晕、失眠、癫痫等神经系统疾病。天麻素和天麻多糖是天麻中两种重要的活性成分,能够有效治疗和改善多种神经系统相关疾病及神经损伤症状。神经退行性疾病是中枢神经系统细胞和组织发生变性和功能障碍导致的一组疾病,综述天麻素和天麻多糖对各神经退行性疾病的保护作用及机制,以期为天麻中各活性成分在神经退行性疾病中的临床应用和机制研究提供参考。

关键词: 天麻素, 天麻多糖, 神经保护, 神经退行性疾病, 阿尔茨海默病, 帕金森病

Abstract: Gastrodia elata, a precious traditional Chinese medicinal herb, has been widely utilized in the treatment of neurological disorders such as headaches, dizziness, insomnia, and epilepsy. Gastrodin and Gastrodia elata polysaccharides, two pivotal bioactive constituents derived from this herb, exhibit therapeutic efficacy in alleviating symptoms and improving outcomes in diverse neurological conditions and neural injuries. Neurodegenerative diseases, characterized by progressive degeneration and functional impairment of cells and tissues within the central nervous system, represent a significant global health burden. This article comprehensively reviews recent advances in understanding the mechanisms and therapeutic potential of gastrodin and Gastrodia elata polysaccharides across various neurodegenerative diseases. The aim is to provide a foundational reference for future clinical applications and mechanistic investigations of these bioactive components in the management of neurodegenerative pathologies.

Key words: Gastrodin, Gastrodia elata polysaccharides, neuroprotection, neurodegenerative diseases, Alzheimer disease, Parkinson disease

中图分类号:

R285

李诗黛,王红杰. 天麻对神经退行性疾病的作用及其机制研究进展[J]. 医学研究与教育, 2025, 42(4): 1-9.

参考文献

[1] QI S, YIN P, WANG L, et al. Prevalence of Parkinson's disease: acommunity-based study in China[J].Mov Disord, 2021, 36(12): 2940-2944. DOI: 10.1002/mds.28762.
[2] CHU Q, CHEN M, SONG D X, et al. Apios americana Medik flowers polysaccharide(AFP-2)attenuates H₂O₂ induced neurotoxicity in PC12 cells[J]. Int J Biol Macromol, 2019, 123: 1115-1124. DOI: 10.1016/j.ijbiomac.2018.11.078.
[3] ARMADA-MOREIRA A, GOMES J I, PINA C C, et al. Going the extra(synaptic)mile: excitotoxicity as the road toward neurodegenerative diseases[J].Front Cell Neurosci, 2020, 14: 90. DOI: 10.3389/fncel.2020.00090.
[4] HEEMELSM T. Neurodegenerative diseases[J]. Nature, 2016,539(7628): 179. DOI: 10.1038/539179a.
[5] ZHANG Y Y, LIN X L, XIA L, et al. Progress on the anti-inflammatory activity and structure-efficacy relationship of polysaccharides from medical and edible homologous traditional Chinese medicines[J]. Molecules, 2024, 29(16): 3852. DOI: 10.3390/molecules29163852.
[6] LI J, LONG Q Y, DING H, et al. Progress in the treatment of central nervous system diseases based on nanosized traditional Chinese medicine[J]. Adv Sci(Weinh), 2024, 11(16): e2308677. DOI: 10.1002/advs.202308677.
[7] YU E, GAO Y G, LI Y Q, et al. An exploration of mechanism of high quality and yield of Gastrodia elata Bl. f. glauca by the isolation, identification and evaluation of Armillaria[J]. BMC Plant Biol, 2022, 22(1): 621. DOI: 10.1186/s12870-022-04007-8.
[8] 雷有成,李建蕊,肖佳佳,等.不同规格等级天麻中多糖的含量测定[C] //中华中医药学会第七次中药分析学术交流会会议论文集.广州:中华医学会, 2014: 243-248.
[9] WAN X H, YIN Y M, ZHOU C Z, et al. Polysaccharides derived from Chinese medicinal herbs: a promising choice of vaccine adjuvants[J]. Carbohydr Polym, 2022, 276: 118739. DOI: 10.1016/j.carbpol.2021.118739.
[10] KNOPMAN D S, AMIEVA H, PETERSEN R C, et al. Alzheimer disease[J]. Nat Rev Dis Primers, 2021, 7(1): 33. DOI: 10.1038/s41572-021-00269-y.
[11] STEPHENSON H G, BETTHAUSER T J, HULLE C A V, et al. Longitudinal neurodegeneration in relation to amyloid pathology among cognitively unimpaired individuals[J]. Alzheimers Dement, 2024, 20(S9): e094055. DOI: 10.1002/alz.094055.
[12] CHEN X Y, HOLTZMAN D M. Emerging roles of innate and adaptive immunity in Alzheimer's disease[J]. Immunity, 2022, 55(12): 2236-2254. DOI: 10.1016/j.immuni.2022.10.016.
[13] LIU B, GAO J M, LI F, et al. Gastrodin attenuates bilateral common carotid artery occlusion-induced cognitive deficits via regulating aβ-related proteins and reducing autophagy and apoptosis in rats[J]. Front Pharmacol, 2018, 9: 405. DOI: 10.3389/fphar.2018.00405.
[14] CHAI A B, HARTZ A M S, GAO X X, et al. New evidence for P-gp-mediated export of amyloid-β PEPTIDES in molecular, blood-brain barrier and neuronal models[J]. Int J Mol Sci, 2020, 22(1): 246. DOI: 10.3390/ijms22010246.
[15] ZHU C H, WANG S T, 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. DOI: 10.1016/j.phymed.2024.156229.
[16] TANG Z, PENG Y Q, JIANG Y, et al. Gastrodin ameliorates synaptic impairment, mitochondrial dysfunction and oxidative stress in N2a/APP cells[J]. Biochem Biophys Res Commun, 2024, 719: 150127. DOI: 10.1016/j.bbrc.2024.150127.
[17] FASINA O B, WANG J Y, MO J X, et al. Gastrodin from Gastrodia elata enhances cognitive function and neuroprotection of AD mice via the regulation of gut microbiota composition and inhibition of neuron inflammation[J]. Front Pharmacol, 2022, 13: 814271. DOI: 10.3389/fphar.2022.814271.
[18] CHU Y P, HIRST W D, FEDEROFF H J, et al. Nigrostriatal tau pathology in Parkinsonism and Parkinson's disease[J]. Brain, 2024, 147(2): 444-457. DOI: 10.1093/brain/awad388.
[19] BLOEM B R, OKUN M S, KLEIN C. Parkinson's disease[J]. Lancet, 2021, 397(10291): 2284-2303. DOI: 10.1016/s0140-6736(21)00218-x.
[20] SADEGHIAN Z, EYVARI-BROOSHGHALAN S, SABAHI M, et al. Post treatment with Gastrodin suppresses oxidative stress and attenuates motor disorders following 6-OHDA induced Parkinson disease[J]. Neurosci Lett, 2022, 790: 136884. DOI: 10.1016/j.neulet.2022.136884.
[21] WANG Y H, LUO K X, LI J R, et al. Focused ultrasound promotes the delivery of gastrodin and enhances the protective effect on dopaminergic neurons in a mouse model of Parkinson's disease[J]. Front Cell Neurosci, 2022, 16: 884788. DOI: 10.3389/fncel.2022.884788.
[22] YAN J Y, YANG Z S, ZHAO N H, et al. Gastrodin protects dopaminergic neurons via insulin-like pathway in a Parkinson's disease model[J]. BMC Neurosci, 2019, 20(1): 31. DOI: 10.1186/s12868-019-0512-x.
[23] 赵文斌.天麻及其有效物质对阿尔兹海默症模型小鼠的作用机制研究[D].兰州:兰州大学, 2019:22-40.
[24] 李光美,王朝群,唐超,等.天麻多糖对阿尔茨海默症小鼠焦虑行为及记忆功能的影响[J].遵义医科大学学报, 2023, 46(3): 227-233, 285. DOI: 10.14169/j.cnki.zunyixuebao.2023.0044.
[25] GAN Q X, PENG M Y, WEI H B, et al. Gastrodia elata polysaccharide alleviates Parkinson's disease via inhibiting apoptotic and inflammatory signaling pathways and modulating the gut microbiota[J]. Food Funct, 2024, 15(6): 2920-2938. DOI: 10.1039/d3fo05169b.
[26] 黄锐,赵健,吴锋,等.电针联合天麻多糖对脑缺血大鼠基底外侧杏仁核巢蛋白、脑源性神经营养因子表达的影响[J].针刺研究, 2016, 41(3): 230-234. DOI: 10.13702/j.1000-0607.2016.03.008.
[27] 王薇,缪化春,吴锋,等.天麻多糖结合电针抑制脑缺血大鼠Meynert基底核神经元损伤和上调BDNF、SCF及VEGF表达[J].中国组织化学与细胞化学杂志, 2017,26(2): 122-128. DOI: 10.16705/j.cnki.1004-1850.2017.02.005.
[28] NEEDHAM B D, KADDURAH-DAOUK R, MAZMANIAN S K. Gut microbial molecules in behavioural and neurodegenerative conditions[J].Nat Rev Neurosci, 2020, 21(12): 717-731. DOI: 10.1038/s41583-020-00381-0.
[29] HOU K J, WU Z X, CHEN X Y, et al. Microbiota in health and diseases[J]. Signal Transduct Target Ther, 2022, 7(1): 135. DOI: 10.1038/s41392-022-00974-4.
[30] LIANG Y, LIU C C, CHENG M M, et al. The link between gut microbiome and Alzheimer's disease: from the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease[J]. Alzheimers Dement, 2024, 20(8): 5771-5788. DOI: 10.1002/alz.14057.
[31] SCHEPERJANS F, AHO V, PEREIRA P A B, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype[J]. Mov Disord, 2015, 30(3): 350-358. DOI: 10.1002/mds.26069.
[32] HUO J Y, LEI M, LI F F, et al. Structural characterization of a polysaccharide from Gastrodia elata and its bioactivity on gut microbiota[J]. Molecules, 2021, 26(15): 4443. DOI: 10.3390/molecules26154443.
[33] HUO J Y, LEI M, ZHOU Y, et al. Structural characterization of two novel polysaccharides from Gastrodia elata and their effects on Akkermansia muciniphila[J]. Int J Biol Macromol, 2021, 186: 501-509. DOI: 10.1016/j.ijbiomac.2021.06.157.
[34] XU D, WU Q Y, LIU W Y, et al. Therapeutic efficacy and underlying mechanisms of Gastrodia elata polysaccharides on dextran sulfate sodium-induced inflammatory bowel disease in mice: modulation of the gut microbiota and improvement of metabolic disorders[J]. Int J Biol Macromol, 2023, 248: 125919. DOI: 10.1016/j.ijbiomac.2023.125919.
[35] GAN Q X, CHEN L L, XIAN J C, et al. Digestive characteristics of Gastrodia elata Blume polysaccharide and related impacts on human gut microbiota in vitro[J]. J Ethnopharmacol, 2024, 328: 118064. DOI: 10.1016/j.jep.2024.118064.
[36] XU Y J, WEI S J, ZHU L Y, et al. Low expression of the intestinal metabolite butyric acid and the corresponding memory pattern regulate HDAC4 to promote apoptosis in rat hippocampal neurons[J]. Ecotoxicol Environ Saf, 2023, 253: 114660. DOI: 10.1016/j.ecoenv.2023.114660.
[37] HU S S, LIN Z Y, ZHAO S B, et al. Pu-erh tea alleviated colitis-mediated brain dysfunction by promoting butyric acid production[J]. Food Chem Toxicol, 2023, 172: 113594. DOI: 10.1016/j.fct.2022.113594.
[38] SINGH K, SETHI P, DATTA S, et al. Advances in gene therapy approaches targeting neuro-inflammation in neurodegenerative diseases[J]. Ageing Res Rev, 2024, 98: 102321. DOI: 10.1016/j.arr.2024.102321.
[39] SARLUS H, HENEKA M T. Microglia in Alzheimer's disease[J]. J Clin Investig, 2017, 127(9): 3240-3249. DOI: 10.1172/jci90606.
[40] ISIK S, YEMAN KIYAK B, AKBAYIR R, et al. Microglia mediated neuroinflammation in Parkinson's disease[J]. Cells, 2023, 12(7): 1012. DOI: 10.3390/cells12071012.
[41] DAI J N, ZONG Y, ZHONG L M, et al. Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways[J]. PLoS One, 2011, 6(7): e21891. DOI: 10.1371/journal.pone.0021891.
[42] SONG J J, LI H, WANG N, et al. Gastrodin ameliorates the lipopolysaccharide-induced neuroinflammation in mice by downregulating miR-107-3p[J]. Front Pharmacol, 2022, 13: 1044375. DOI: 10.3389/fphar.2022.1044375.
[43] 刘萌萌,张伊,张耀元,等.天麻多糖对脂多糖诱导抑郁小鼠的作用及机制研究[J].中国药师, 2021, 24(11): 2018-2023. DOI: 10.19962/j.cnki.issn1008-049X.2021.11.011.
[44] ZHANG Y, YE P, ZHU H, et al. Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway[J]. CNS Neurosci Ther,2024, 30(3): e14456. DOI: 10.1111/cns.14456.
[45] AGIRMAN G, YU K B, HSIAO E Y. Signaling inflammation across the gut-brain axis[J].Science, 2021, 374(6571): 1087-1092. DOI: 10.1126/science.abi6087.
[46] CLAUDINO DOS SANTOS J C, LIMA M P P, BRITO G A C, et al. Role of enteric Glia and microbiota-gut-brain axis in parkinson disease pathogenesis[J]. Ageing Res Rev, 2023, 84: 101812. DOI: 10.1016/j.arr.2022.101812.
[47] SPILSBURY A, MIWA S, ATTEMS J, et al. The role of telomerase protein TERT in Alzheimer's disease and in tau-related pathology in vitro[J]. J Neurosci, 2015, 35(4): 1659-1674. DOI: 10.1523/JNEUROSCI.2925-14.2015.
[48] JIANG T, CHU J, CHEN H, et al. Gastrodin inhibits H₂O₂-induced ferroptosis through its antioxidative effect in rat glioma cell line C6[J]. Biol Pharm Bull, 2020, 43(3): 480-487. DOI: 10.1248/bpb.b19-00824.
[49] WU S, HUANG R, ZHANG R Q, et al. Gastrodin and gastrodigenin improve energy metabolism disorders and mitochondrial dysfunction to antagonize vascular dementia[J]. Molecules, 2023, 28(6): 2598. DOI: 10.3390/molecules28062598.
[50] HE J Z, LI X, YANG S P, et al. Gastrodin extends the lifespan and protects against neurodegeneration in the Drosophila PINK1 model of Parkinson's disease[J]. Food Funct, 2021, 12(17): 7816-7824. DOI: 10.1039/d1fo00847a.
[51] JI N, LIU P, ZHANG N, et al. Comparison on bioactivities and characteristics of polysaccharides from four varieties of Gastrodia elata blume[J]. Front Chem, 2022, 10: 956724. DOI: 10.3389/fchem.2022.956724.
[52] DU C J, LIU X Y, ALGADI H, et al. Polysaccharide extraction optimization, monosaccharide composition, and antioxidant activity analysis of different varieties of Gastrodia elata Bl aerial parts[J]. Biomass Convers Biorefin, 2024, 14(23): 29353-29365. DOI: 10.1007/s13399-023-05014-x.
[53] 侯敏娜,侯少平.陕产天麻多糖抗氧化活性实验研究[J].陕西农业科学, 2018, 64(6): 31-32, 71.
[54] CHEN X, CAO D X, ZHOU L, et al. Structure of a polysaccharide from Gastrodia elata Bl., and oligosaccharides prepared thereof with anti-pancreatic cancer cell growth activities[J]. Carbohydr Polym, 2011, 86(3): 1300-1305. DOI: 10.1016/j.carbpol.2011.06.029.
[55] 明建,曾凯芳,吴素蕊,等.天麻多糖PGEB-3-H对东莨菪碱所致小鼠学习记忆障碍的影响[J].食品科学, 2010, 31(3): 246-249.
[56] 谢学渊,任婷麟,安扬.天麻多糖对谷氨酸损伤HT22细胞的保护作用[J].解放军药学学报, 2016, 32(2): 120-123.DOI: 10.3969/j.issn.1008-9926.2016.02.005.
[57] MO J, ENKHJARGAL B, TRAVIS Z D, et al. AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP-2 pathway after subarachnoid hemorrhage in rats[J]. Redox Biol, 2019, 20: 75-86. DOI: 10.1016/j.redox.2018.09.022.
[58] 谢学渊,晁衍明,杜珍,等.天麻多糖的抗衰老作用[J].解放军药学学报, 2010, 26(3): 206-209.DOI: 10.3969/j.issn.1008-9926.2010.03.06.
[59] SPIRES-JONES T L, ATTEMS J, THAL D R. Interactions of pathological proteins in neurodegenerative diseases[J]. Acta Neuropathol, 2017, 134(2): 187-205. DOI: 10.1007/s00401-017-1709-7.
[60] CEN X F, ZHANG M K, ZHOU M X, et al. Mitophagy regulates neurodegenerative diseases[J]. Cells, 2021, 10(8): 1876. DOI: 10.3390/cells10081876.
[61] WANG X S, TIAN Z, ZHANG N, et al. Protective effects of gastrodinagainst autophagy-mediated astrocyte death[J]. Phytother Res, 2016, 30(3): 386-396. DOI: 10.1002/ptr.5538.
[62] LEI X, YUAN Y, ZOU Q. The role and mechanism of gastrodin in the medial prefrontal cortex autophagy of PTSD rats[J]. Int J Clin Exp Pathol, 2020, 13(5): 989-994.
[63] STRACK R. Deep learning in imaging[J]. Nat Methods, 2019, 16(1): 17. DOI: 10.1038/s41592-018-0267-9.
[64] ZHOU Z D, YI L X, WANG D Q, et al. Role of dopamine in the pathophysiology of Parkinson's disease[J]. Transl Neurodegener, 2023, 12(1): 44. DOI: 10.1186/s40035-023-00378-6.
[65] CHEN Z R, HUANG J B, YANG S L, et al. Role of cholinergic signaling in Alzheimer's disease[J].Molecules, 2022, 27(6): 1816. DOI: 10.3390/molecules27061816.
[66] 史华,何琦,娄元俊,等.天麻多糖对脑瘫幼鼠脑内神经递质的影响[J].中国实验方剂学杂志, 2017, 23(23): 140-145. DOI: 10.13422/j.cnki.syfjx.2017230140.