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Chinese Herbal Medicine Adjusting Brain Microenvironment via Mediating Central Nervous System Lymphatic Drainage in Alzheimer’s Disease

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Abstract

Due to its complex pathogenesis and lack of effective therapeutic methods, Alzheimer’s disease (AD) has become a severe public health problem worldwide. Recent studies have discovered the function of central nervous system lymphatic drainage, which provides a new strategy for the treatment of AD. Chinese herbal medicine (CHM) has been considered as a cure for AD for hundreds of years in China, and its effect on scavenging β-amyloid protein in the brain of AD patients has been confirmed. In this review, the mechanism of central nervous system lymphatic drainage and the regulatory functions of CHM on correlation factors were briefly summarized. The advances in our understanding regarding the treatment of AD via regulating the central lymphatic system with CHM will promote the clinical application of CHM in AD patients and the discovery of new therapeutic drugs.

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References

  1. Chuah YK, Basir R, Talib H, et al. Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflam 2013;2013:403460.

    PubMed  PubMed Central  Google Scholar 

  2. Alteri E, Guizzaro L. Be open about drug failures to speed up research. Nature 2018;563:317–319.

    Article  CAS  PubMed  Google Scholar 

  3. Morrone CD, Liu M, Black SE, et al. Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms. Front Aging Neurosci 2015;7:64.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Attems J, Jellinger K, Thal DR, et al. Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2011;37:75–93.

    Article  CAS  PubMed  Google Scholar 

  5. Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 2012;4:147ra111.

    Article  Google Scholar 

  6. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015;523:337–341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Boland B, Yu WH, Corti O, et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nat Rev Drug Discov 2018;17:660–688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zeng Q, Siu W, Li L, et al. Autophagy in Alzheimer’s disease and promising modulatory effects of herbal medicine. Exp Gerontol 2019;119:100–110.

    Article  PubMed  Google Scholar 

  9. Jarrell JT, Gao L, Cohen DS, et al. Network medicine for Alzheimer’s disease and traditional Chinese medicine. Molecules 2018;23.

  10. Revett TJ, Baker GB, Jhamandas J, et al. Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci 2013;38:6–23.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cai Z, Liu N, Wang C, et al. Role of RAGE in Alzheimer’s disease. Cell Mol Neurobiol 2016;36:483–495.

    Article  CAS  PubMed  Google Scholar 

  12. Liu L, Wan W, Xia S, et al. Dysfunctional Wnt/β -catenin signaling contributes to blood-brain barrier breakdown in Alzheimer’s disease. Neurochem Int 2014;75:19–25.

    Article  CAS  PubMed  Google Scholar 

  13. Deane R, Sagare A, Zlokovic BV. The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer’s disease. Curr Pharm Des 2008;14:1601–1605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Deane R, Wu Z, Sagare A, et al. LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 2004;43:333–344.

    Article  CAS  PubMed  Google Scholar 

  15. Miller MC, Tavares R, Johanson CE, et al. Hippocampal RAGE immunoreactivity in early and advanced Alzheimer’s disease. Brain Res 2008;1230:273–280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sharma HS, Castellani RJ, Smith MA, et al. The blood-brain barrier in Alzheimer’s disease: novel therapeutic targets and nanodrug delivery. Int Rev Neurobiol 2012;102:47–90.

    Article  CAS  PubMed  Google Scholar 

  17. Da Mesquita S, Louveau A, Vaccari A, et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature 2018;560:185–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang L, Zhang Y, Zhao Y, et al. Deep cervical lymph node ligation aggravates AD-like pathology of APP/PS1 mice. Brain Pathol 2019;29:176–192.

    Article  CAS  PubMed  Google Scholar 

  19. Xu Z, Xiao N, Chen Y, et al. Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits. Mol Neurodegener 2015;10:58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Smith AJ, Duan T, Verkman AS. Aquaporin-4 reduces neuropathology in a mouse model of Alzheimer’s disease by remodeling peri-plaque astrocyte structure. Acta Neuropathol Commun 2019;7:74.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gao X, Ming J, Liu S, et al. Sevoflurane enhanced the clearance of Aβ 1–40 in hippocampus under surgery via up-regulating AQP-4 expression in astrocyte. Life Sci 2019;221:143–151.

    Article  CAS  PubMed  Google Scholar 

  22. Moftakhar P, Lynch MD, Pomakian JL, et al. Aquaporin expression in the brains of patients with or without cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2010;69:1201–1209.

    Article  CAS  PubMed  Google Scholar 

  23. Yang J, Lunde LK, Nuntagij P, et al. Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer’s disease. J Alzheimers Dis 2011;27:711–722.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang J, Zhan Z, Li X, et al. Intermittent fasting protects against Alzheimer’s disease possible through restoring aquaporin-4 polarity. Front Mol Neurosci 2017;10:395.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yin M, Pu T, Wang L, et al. Astroglial water channel aquaporin 4-mediated glymphatic clearance function: a determined factor for time-sensitive treatment of aerobic exercise in patients with Alzheimer’s disease. Med Hypotheses 2018;119:18–21.

    Article  CAS  PubMed  Google Scholar 

  26. Noell S, Wolburg-Buchholz K, Mack AF, et al. Evidence for a role of dystroglycan regulating the membrane architecture of astroglial endfeet. Eur J Neurosci 2011;33:2179–2186.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Noell S, Fallier-Becker P, Deutsch U, et al. Agrin defines polarized distribution of orthogonal arrays of particles in astrocytes. Cell Tissue Res 2009;337:185–195.

    Article  CAS  PubMed  Google Scholar 

  28. Amiry-Moghaddam M, Frydenlund DS, Ottersen OP. Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the physiology and pathophysiology of water transport. Neuroscience 2004;129:999–1010.

    Article  CAS  PubMed  Google Scholar 

  29. Neely JD, Amiry-Moghaddam M, Ottersen OP, et al. Syntrophin-dependent expression and localization of aquaporin-4 water channel protein. Proc Natl Acad Sci USA 2001;98:14108–14113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Qiu GP, Xu J, Zhuo F, et al. Loss of AQP4 polarized localization with loss of β -dystroglycan immunoreactivity may induce brain edema following intracerebral hemorrhage. Neurosci Lett 2015;588:42–48.

    Article  CAS  PubMed  Google Scholar 

  31. Zhao XL, Li GZ, Sun B, et al. MMP-mediated cleavage of beta-dystroglycan in myelin sheath is involved in autoimmune neuritis. Biochem Biophys Res Commun 2010;392:551–556.

    Article  CAS  PubMed  Google Scholar 

  32. Yan W, Zhao X, Chen H, et al. β-Dystroglycan cleavage by matrix metalloproteinase-2/-9 disturbs aquaporin-4 polarization and influences brain edema in acute cerebral ischemia. Neuroscience 2016;326:141–157.

    Article  CAS  PubMed  Google Scholar 

  33. Bruno MA, Mufson EJ, Wuu J, et al. Increased matrix metalloproteinase 9 activity in mild cognitive impairment. J Neuropathol Exp Neurol 2009;68:1309–1318.

    Article  CAS  PubMed  Google Scholar 

  34. Lorenzl S, Albers DS, Relkin N, et al. Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer’s disease. Neurochem Int 2003;43:191–196.

    Article  CAS  PubMed  Google Scholar 

  35. Montagne A, Nation DA, Sagare AP, et al. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nature 2020;581:71–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yang W, Wu Q, Yuan C, et al. Aquaporin-4 mediates astrocyte response to β -amyloid. Mol Cell Neurosci 2012;49:406–414.

    Article  CAS  PubMed  Google Scholar 

  37. Csernansky JG, Dong H, Fagan AM, et al. Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia. Am J Psychiatry 2006;163:2164–2169.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Popp J, Wolfsgruber S, Heuser I, et al. Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer’s type. Neurobiol Aging 2015;36:601–607.

    Article  CAS  PubMed  Google Scholar 

  39. Green KN, Billings LM, Roozendaal B, et al. Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer’s disease. J Neurosci 2006;26:9047–9056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Baglietto-Vargas D, Medeiros R, Martinez-Coria H, et al. Mifepristone alters amyloid precursor protein processing to preclude amyloid beta and also reduces tau pathology. Biol Psychiatry 2013;74:357–366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wei F, Song J, Zhang C, et al. Chronic stress impairs the aquaporin-4-mediated glymphatic transport through glucocorticoid signaling. Psychopharmacology (Berl) 2019;236:1367–1384.

    Article  CAS  Google Scholar 

  42. Breslin JW. Mechanical forces and lymphatic transport. Microvasc Res 2014;96:46–54.

    Article  PubMed  Google Scholar 

  43. Antila S, Karaman S, Nurmi H, et al. Development and plasticity of meningeal lymphatic vessels. J Exp Med 2017;214:3645–3667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cha YR, Fujita M, Butler M, et al. Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature. Dev Cell 2012;22:824–836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jha SK, Rauniyar K, Karpanen T, et al. Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1. Sci Rep 2017;7:4916.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Louveau A, Herz J, Alme MN, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci 2018;21:1380–1391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Nurmi H, Saharinen P, Zarkada G, et al. VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption. EMBO Mol Med 2015;7:1418–1425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tutunea-Fatan E, Majumder M, Xin X, et al. The role of CCL21/CCR7 chemokine axis in breast cancer-induced lymphangiogenesis. Mol Cancer 2015;14:35.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Yongjun Y, Shuyun H, Lei C, et al. Atorvastatin suppresses glioma invasion and migration by reducing microglial MT1-MMP expression. J Neuroimmunol 2013;260:1–8.

    Article  PubMed  Google Scholar 

  50. Langenfurth A, Rinnenthal JL, Vinnakota K, et al. Membranetype 1 metalloproteinase is upregulated in microglia/brain macrophages in neurodegenerative and neuroinflammatory diseases. J Neurosci Res 2014;92:275–286.

    Article  CAS  PubMed  Google Scholar 

  51. Wong HL, Jin G, Cao R, et al. MT1-MMP sheds LYVE-1 on lymphatic endothelial cells and suppresses VEGF-C production to inhibit lymphangiogenesis. Nat Commun 2016;7:10824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang Y, Lin C, Zhang L, et al. Cognitive improvement during treatment for mild Alzheimer’s disease with a Chinese herbal formula: a randomized controlled trial. PLoS One 2015;10:e0130353.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Furukawa K, Tomita N, Uematsu D, et al. Randomized doubleblind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer’s disease. Geriatr Gerontol Int 2017;17:211–218.

    Article  PubMed  Google Scholar 

  54. Yang Y, Liu JP, Fang JY, et al. Effect and safety of Huannao Yicong Formula in patients with mild-to-moderate Alzheimer’s disease: a randomized, double-blinded, donepezil-controlled trial. Chin J Integr Med 2019;25:574–581.

    Article  PubMed  Google Scholar 

  55. Liu P, Kong M, Liu S, et al. Effect of reinforcing kidney-essence, removing phlegm, and promoting mental therapy on treating Alzheimer’s disease. J Tradit Chin Med 2013;33:449–454.

    Article  PubMed  Google Scholar 

  56. Feng CZ, Cao L, Luo D, et al. Dendrobium polysaccharides attenuate cognitive impairment in senescence-accelerated mouse prone 8 mice via modulation of microglial activation. Brain Res 2019;1704:1–10.

    Article  CAS  PubMed  Google Scholar 

  57. Huang Y, Guo B, Shi B, et al. Chinese herbal medicine Xueshuantong enhances cerebral blood flow and improves neural functions in Alzheimer’s disease mice. J Alzheimers Dis 2018;63:1089–1107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhang Z, Wang X, Zhang D, et al. Geniposide-mediated protection against amyloid deposition and behavioral impairment correlates with downregulation of mTOR signaling and enhanced autophagy in a mouse model of Alzheimer’s disease. Aging (Albany NY) 2019;11:536–548.

    Article  Google Scholar 

  59. Kawakami Z, Ikarashi Y, Kase Y. Glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid in glycyrrhiza, a constituent herb of yokukansan, ameliorate thiamine deficiency-induced dysfunction of glutamate transport in cultured rat cortical astrocytes. Eur J Pharmacol 2010;626:154–158.

    Article  CAS  PubMed  Google Scholar 

  60. Zhu SM, Xiong XX, Zheng YY, et al. Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent pathway in an astrocyte model of cerebral ischemia/reoxygenation. Anesth Analg 2009;109:1493–1499.

    Article  CAS  PubMed  Google Scholar 

  61. Ko HM, Joo SH, Kim P, et al. Effects of Korean Red Ginseng extract on tissue plasminogen activator and plasminogen activator inhibitor-1 expression in cultured rat primary astrocytes. J Ginseng Res 2013;37:401–412.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Chu H, Ding H, Tang Y, et al. Erythropoietin protects against hemorrhagic blood-brain barrier disruption through the effects of aquaporin-4. Lab Invest 2014;94:1042–1053.

    Article  CAS  PubMed  Google Scholar 

  63. Qi LL, Fang SH, Shi WZ, et al. CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes. Life Sci 2011;88:50–56.

    Article  CAS  PubMed  Google Scholar 

  64. Kaufmann D, Kaur Dogra A, Tahrani A, et al. Extracts from traditional Chinese medicinal plants inhibit acetylcholinesterase, a known Alzheimer’s disease target. Molecules 2016;21:1161.

    Article  PubMed Central  Google Scholar 

  65. Li Y, Wang B, Liu C, et al. Inhibiting c-Jun N-terminal kinase (JNK)-mediated apoptotic signaling pathway in PC12 cells by a polysaccharide (CCP) from Coptis chinensis against amyloid-β (Aβ)-induced neurotoxicity. Int J Biol Macromol 2019;134:565–574.

    Article  CAS  PubMed  Google Scholar 

  66. Li J, Ni L, Li B, et al. Coptis Chinensis affects the function of glioma cells through the down-regulation of phosphorylation of STAT3 by reducing HDAC3. BMC Complement Altern Med 2017;17:524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhao C, Zhang H, Li H, et al. Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice. Neuropharmacology 2017;116:18–29.

    Article  CAS  PubMed  Google Scholar 

  68. Gao C, Liu Y, Jiang Y, et al. Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced Alzheimer rat model. Brain Pathol 2014;24:261–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Li C, Wang X, Cheng F, et al. Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system. Eur J Pharmacol 2019;854:224–231.

    Article  CAS  PubMed  Google Scholar 

  70. Liu C, Chen K, Lu Y, et al. Catalpol provides a protective effect on fibrillary A β 1-42-induced barrier disruption in an in vitro model of the blood-brain barrier. Phytother Res 2018;32:1047–1055.

    Article  CAS  PubMed  Google Scholar 

  71. Yang CM, Yang SH, Lee TH, et al. Evaluation of anti-inflammatory effects of Helminthostachys zeylanica extracts via inhibiting bradykinin-induced MMP-9 expression in brain astrocytes. Mol Neurobiol 2016;53:5995–6005.

    Article  PubMed  Google Scholar 

  72. Hu Q, Yu B, Chen Q, et al. Effect of Linguizhugan Decoction on neuroinflammation and expression disorder of the amyloid β -related transporters RAGE and LRP-1 in a rat model of Alzheimer’s disease. Mol Med Rep 2018;17:827–834.

    CAS  PubMed  Google Scholar 

  73. Yang P, Chen A, Qin Y, et al. Buyang Huanwu Decoction combined with BMSCs transplantation promotes recovery after spinal cord injury by rescuing axotomized red nucleus neurons. J Ethnopharmacol 2019;228:123–131.

    Article  PubMed  Google Scholar 

  74. Liu B, Liu G, Wang Y, et al. Protective effect of Buyang Huanwu Decoction on neurovascular unit in Alzheimer’s disease cell model via inflammation and RAGE/LRP1 pathway. Med Sci Monit 2019;25:7813–7825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Jayasingh Chellammal HS, Veerachamy A, Ramachandran D, et al. Neuroprotective effects of 1 δ` -1`-acetoxyeugenol acetate on Aβ (25-35) induced cognitive dysfunction in mice. Biomed Pharmacother 2019;109:1454–1461.

    Article  CAS  PubMed  Google Scholar 

  76. Zhou YQ, Yang ZL, Xu L, et al. Akebia saponin D, a saponin component from Dipsacus asper Wall, protects PC 12 cells against amyloid-beta induced cytotoxicity. Cell Biol Int 2009;33:1102–1110.

    Article  CAS  PubMed  Google Scholar 

  77. Wang Y, Shen J, Yang X, et al. Akebia saponin D reverses corticosterone hypersecretion in an Alzheimer’s disease rat model. Biomed Pharmacother 2018;107:219–225.

    Article  CAS  PubMed  Google Scholar 

  78. Leung KW, Ng HM, Tang MK, et al. Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1 α to promote angiogenesis. Angiogenesis 2011;14:515–522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yu J, Mao L, Guan L, et al. Ginsenoside Rg1 enhances lymphatic transport of intrapulmonary silica via VEGF-C/VEGFR-3 signaling in silicotic rats. Biochem Biophys Res Commun 2016;472:182–188.

    Article  CAS  PubMed  Google Scholar 

  80. Jia F, Mou L, Ge H. Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210. Int J Immunopathol Pharmacol 2019;33:2058738419866021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Meng ZY, Kang HL, Duan W, et al. MicroRNA-210 promotes accumulation of neural precursor cells around ischemic foci after cerebral ischemia by regulating the SOCS1-STAT3-VEGF-C pathway. J Am Heart Assoc 2018;7:e005052.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Li J, Chen Y, Zhang L, et al. Total saponins of panaxnotoginseng promotes lymphangiogenesis by activation VEGF-C expression of lymphatic endothelial cells. J Ethnopharmacol 2016;193:293–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yang XN, Li CS, Chen C, et al. Protective effect of Shouwu Yizhi Decoction against vascular dementia by promoting angiogenesis. Chin J Nat Med 2017;15:740–750.

    CAS  PubMed  Google Scholar 

  84. Duan MH, Wang LN, Jiang YH, et al. Angelica sinensis reduced Aβ -induced memory impairment in rats. J Drug Target 2016;24:340–347.

    Article  CAS  PubMed  Google Scholar 

  85. Piltonen M, Planken A, Leskelä O, et al. Vascular endothelial growth factor C acts as a neurotrophic factor for dopamine neurons in vitro and in vivo. Neuroscience 2011;192:550–563.

    Article  CAS  PubMed  Google Scholar 

  86. Luo L, Kim SW, Lee HK, et al. Anti-Zn2+-toxicity of 4-hydroxybenzyl alcohol in astrocytes and neurons contribute to a robust neuroprotective effects in the postischemic brain. Cell Mol Neurobiol 2018;38:615–626.

    Article  CAS  PubMed  Google Scholar 

  87. Chen WC, Lai YS, Lin SH, et al. Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling. J Ethnopharmacol 2016;182:190–199.

    Article  CAS  PubMed  Google Scholar 

  88. Kim BW, Koppula S, Kim JW, et al. Modulation of LPS-stimulated neuroinflammation in BV-2 microglia by Gastrodia elata: 4-hydroxybenzyl alcohol is the bioactive candidate. J Ethnopharmacol 2012;139:549–557.

    Article  CAS  PubMed  Google Scholar 

  89. Luo L, Kim SW, Lee HK, et al. Anti-oxidative effects of 4-hydroxybenzyl alcohol in astrocytes confer protective effects in autocrine and paracrine manners. PLoS One 2017;12:e0177322.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Zhang X, Fei X, Tao W, et al. Neuroprotective effect of Modified Xijiao Dihuang Decoction against oxygen-glucose deprivation and reoxygenation-induced injury in PC12 cells: involvement of TLR4-MyD88/NF-κ B signaling pathway. Evid Based Complement Alternat Med 2017;2017:3848595.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Fei X, Zhang X, Wang Q, et al. Xijiao Dihuang Decoction alleviates ischemic brain injury in MCAO rats by regulating inflammation, neurogenesis, and angiogenesis. Evid Based Complement Alternat Med 2018;2018:5945128.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Wan J, Wan H, Yang R, et al. Protective effect of Danhong Injection combined with Naoxintong Capsule on cerebral ischemia-reperfusion injury in rats. J Ethnopharmacol 2018;211:348–357.

    Article  PubMed  Google Scholar 

  93. Pang MF, Georgoudaki AM, Lambut L, et al. TGF-β 1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis. Oncogene 2016;35:748–760.

    Article  CAS  PubMed  Google Scholar 

  94. Yang Z, Zhao T, Zou Y, et al. Curcumin inhibits microglia inflammation and confers neuroprotection in intracerebral hemorrhage. Immunol Lett 2014;160:89–95.

    Article  CAS  PubMed  Google Scholar 

  95. Lu L, Li HQ, Li JH, et al. Neuroprotection of Sanhua Decoction against focal cerebral ischemia/reperfusion injury in rats through a mechanism targeting aquaporin 4. Evid Based Complement Alternat Med 2015;2015:584245.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Cheng CY, Ho TY, Hsiang CY, et al. Angelica sinensis exerts angiogenic and anti-apoptotic effects against cerebral ischemia-reperfusion injury by activating p38MAPK/HIF-1/VEGF-A signaling in rats. Am J Chin Med 2017;45:1683–1708.

    Article  PubMed  Google Scholar 

  97. Zhang M, Cui Z, Cui H, et al. Astaxanthin alleviates cerebral edema by modulating NKCC1 and AQP4 expression after traumatic brain injury in mice. BMC Neurosci 2016;17:60.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210046, China

    Xi-bin Zhou, Yu-xing Zhang, Chun-xiang Zhou & Jun-jie Ma

  2. Department of Traditional Chinese Medicine, Nanjing BenQ Hospital, Nanjing, 210036, China

    Chun-xiang Zhou

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Zhou XB and Ma JJ undertook data collation and manuscript writing, Zhang YX and Zhou CX polished the manuscript.

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Correspondence to Jun-jie Ma.

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The authors declare that there are no conflicts of interest regarding the publication of this paper.

Supported by the National Natural Science Foundation of China (No. 81774021) and Yushan Traditional Chinese Medicine Classic Inheritance Award Fund

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Chinese Herbal Medicine Adjusting Brain Microenvironment via Mediating Central Nervous System Lymphatic Drainage in Alzheimer’s Disease

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Zhou, Xb., Zhang, Yx., Zhou, Cx. et al. Chinese Herbal Medicine Adjusting Brain Microenvironment via Mediating Central Nervous System Lymphatic Drainage in Alzheimer’s Disease. Chin. J. Integr. Med. 28, 176–184 (2022). https://doi.org/10.1007/s11655-021-3342-5

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