Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer's disease

Brain, Behavior, and Immunity

Volumn 46, Issue , 2015, Pages 121-131

  Liu, Xu ^a   Hao, Wenlin ^a   Qin, Yiren ^a,b   Decker, Yann ^a   Wang, Xuan ^c   Burkart, Martin ^d   Schötz, Karl ^d   Menger, Michael D ^a   Fassbender, Klaus ^a   Liu, Yang ^a  

^a SAARLAND UNIVERSITY   (Germany)

^b SOOCHOW UNIVERSITY   (China)

^c Putuo People's Hospital ^*  (China)

^d DR WILLMAR SCHWABE GMBH AND CO KG   (Germany)

Author keywords

Alzheimer's disease; Autophagy; A ; Inflammation; Microglia; Neurodegeneration

Indexed keywords

AMYLOID PRECURSOR PROTEIN; ANTIINFLAMMATORY AGENT; BETA SECRETASE; CRYOPYRIN; GINKGO BILOBA EXTRACT; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; MUNC18 1; MUNC18 PROTEIN; POSTSYNAPTIC DENSITY PROTEIN 95; PROTEIN; SYNAPTOSOME ASSOCIATED PROTEIN 25; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; DLGH4 PROTEIN, MOUSE; GINKGO BILOBA EXTRACT 761; GUANYLATE KINASE; MEMBRANE PROTEIN; NEUROPROTECTIVE AGENT; PLANT EXTRACT; STXBP1 PROTEIN, MOUSE; SYNAPTOSOMAL ASSOCIATED PROTEIN 25;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; BARNES MAZE TEST; BRAIN HOMOGENATE; CELLULAR SECRETION; COGNITION; CONTROLLED STUDY; DIET SUPPLEMENTATION; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG TOLERABILITY; ENZYME ACTIVATION; FEMALE; GINKGO BILOBA; HUMAN; INVESTIGATIVE PROCEDURES; LONG TERM CARE; MICROGLIA; MOUSE; NONHUMAN; PATHOLOGY; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEPLETION; PROTEIN STRUCTURE; QUANTITATIVE ANALYSIS; RANDOMIZED CONTROLLED TRIAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE; WESTERN BLOTTING; ANIMAL; BRAIN; DRUG EFFECTS; MAZE TEST; METABOLISM; NERVE CELL;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BRAIN; GINKGO BILOBA; GUANYLATE KINASE; MAZE LEARNING; MEMBRANE PROTEINS; MICE; MICE, TRANSGENIC; MUNC18 PROTEINS; NEURONS; NEUROPROTECTIVE AGENTS; PLANT EXTRACTS; SYNAPTOSOMAL-ASSOCIATED PROTEIN 25;

EID: 84928827263     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2015.01.011     Document Type: Article

References (60)

1. Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., Fiebich B.L., Finch C.E., Frautschy S., Griffin W.S., Hampel H., Hull M., Landreth G., Lue L., Mrak R., Mackenzie I.R., McGeer P.L., O'Banion M.K., Pachter J., Pasinetti G., Plata-Salaman C., Rogers J., Rydel R., Shen Y., Streit W., Strohmeyer R., Tooyoma I., Van Muiswinkel F.L., Veerhuis R., Walker D., Webster S., Wegrzyniak B., Wenk G., Wyss-Coray T. Inflammation and Alzheimer's disease. Neurobiol. Aging 2000, 21:383-421.
2. Augustin S., Rimbach G., Augustin K., Schliebs R., Wolffram S., Cermak R. Effect of a short- and long-term treatment with Ginkgo biloba extract on amyloid precursor protein levels in a transgenic mouse model relevant to Alzheimer's disease. Arch. Biochem. Biophys. 2009, 481:177-182.
3. Bastianetto S., Ramassamy C., Doré S., Christen Y., Poirier J., Quirion R. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur. J. Neurosci. 2000, 12:1882-1890.
4. Biber A., Koch E. Bioavailability of ginkgolides and bilobalide from extracts of Ginkgo biloba using GC/MS. Planta Med. 1999, 65:192-193.
5. Birks J., Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst. Rev. 2009, 1:CD003120.
6. Chishti M.A., Yang D.S., Janus C., Phinney A.L., Horne P., Pearson J., Strome R., Zuker N., Loukides J., French J., Turner S., Lozza G., Grilli M., Kunicki S., Morissette C., Paquette J., Gervais F., Bergeron C., Fraser P.E., Carlson G.A., George-Hyslop P.S., Westaway D. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J. Biol. Chem. 2001, 276:21562-21570.
7. Cho M.H., Cho K., Kang H.J., Jeon E.Y., Kim H.S., Kwon H.J., Kim H.M., Kim D.H., Yoon S.Y. Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy 2014, 10:1761-1775.
8. Chuang S.Y., Lin C.H., Fang J.Y. Natural compounds and aging: between autophagy and inflammasome. Biomed. Res. Int. 2014, 2014:297293.
9. Chuang S.Y., Yang C.H., Chou C.C., Chiang Y.P., Chuang T.H., Hsu L.C. TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:16079-16084.
10. Colciaghi F., Borroni B., Zimmermann M., Bellone C., Longhi A., Padovani A., Cattabeni F., Christen Y., Di Luca M. Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. Neurobiol. Dis. 2004, 16:454-460.
11. Dahlgren K.N., Manelli A.M., Stine W.B., Baker L.K., Krafft G.A., LaDu M.J. Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J. Biol. Chem. 2002, 277:32046-32053.
12. DeFeudis F.V., Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr. Drug Targets 2000, 1:25-58.
13. DeKosky S.T., Williamson J.D., Fitzpatrick A.L., Kronmal R.A., Ives D.G., Saxton J.A., Lopez O.L., Burke G., Carlson M.C., Fried L.P., Kuller L.H., Robbins J.A., Tracy R.P., Woolard N.F., Dunn L., Snitz B.E., Nahin R.L., Furberg C.D. Ginkgo evaluation of memory (GEM) study investigators. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 2008, 300:2253-2262.
14. Dodge H.H., Zitzelberger T., Oken B.S., Howieson D., Kaye J. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline. Neurology 2008, 70:1809-1817.
15. Eckert A. Mitochondrial effects of Ginkgo biloba extract. Int. Psychogeriatr. 2012, 24(Suppl. 1):S18-S20.
16. Fassbender K., Walter S., Kühl S., Landmann R., Ishii K., Bertsch T., Stalder A.K., Muehlhauser F., Liu Y., Ulmer A.J., Rivest S., Lentschat A., Gulbins E., Jucker M., Staufenbiel M., Brechtel K., Walter J., Multhaup G., Penke B., Adachi Y., Hartmann T., Beyreuther K. The LPS receptor (CD14) links innate immunity with Alzheimer's disease. FASEB J. 2004, 18:203-205.
17. Gundersen H.J., Jensen E.B. The efficiency of systematic sampling in stereology and its prediction. J. Microsc. 1987, 147:229-263.
18. Haines D.D., Varga B., Bak I., Juhasz B., Mahmoud F.F., Kalantari H., Gesztelyi R., Lekli I., Czompa A., Tosaki A. Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: a comparison with ibuprofen. Phytother. Res. 2011, 25:128-136.
19. Halle A., Hornung V., Petzold G.C., Stewart C.R., Monks B.G., Reinheckel T., Fitzgerald K.A., Latz E., Moore K.J., Golenbock D.T. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat. Immunol. 2008, 9:857-865.
20. Hao W., Liu Y., Liu S., Walter S., Grimm M.O., Kiliaan A.J., Penke B., Hartmann T., Rübe C.E., Menger M.D., Fassbender K. Myeloid differentiation factor 88-deficient bone marrow cells improve Alzheimer's disease-related symptoms and pathology. Brain 2011, 134:278-292.
21. He P., Zhong Z., Lindholm K., Berning L., Lee W., Lemere C., Staufenbiel M., Li R., Shen Y. Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice. J. Cell Biol. 2007, 178:829-841.
22. Heneka M.T., Kummer M.P., Latz E. Innate immune activation in neurodegenerative disease. Nat. Rev. Immunol. 2014, 14:463-477.
23. Heneka M.T., Kummer M.P., Stutz A., Delekate A., Schwartz S., Vieira-Saecker A., Griep A., Axt D., Remus A., Tzeng T.C., Gelpi E., Halle A., Korte M., Latz E., Golenbock D.T. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013, 493:674-678.
24. Herrschaft H., Nacu A., Likhachev S., Sholomov I., Hoerr R., Schlaefke S. Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240mg. J. Psychiatr. Res. 2012, 46:716-723.
25. Hou Y., Aboukhatwa M.A., Lei D.L., Manaye K., Khan I., Luo Y. Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice. Neuropharmacology 2010, 58:911-920.
26. Huang Y., Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell 2012, 148:1204-1222.
27. Ihl R., Bachinskaya N., Korczyn A.D., Vakhapova V., Tribanek M., Hoerr R., Napryeyenko O. Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial. Int. J. Geriatr. Psychiatry 2011, 26:1186-1194. GOTADAY Study Group.
28. Jaturapatporn D., Isaac M.G., McCleery J., Tabet N. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Cochrane Database Syst. Rev. 2012, 2:CD006378.
29. Jiang L., Su L., Cui H., Ren J., Li C. Ginkgo biloba extract for dementia: a systematic review. Shanghai Arch. Psychiatry 2013, 25:10-21.
30. Kasper S. Clinical data in early intervention. Int. Psychogeriatr. 2012, 24(Suppl. 1):S41-S45.
31. Klionsky D.J., et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 2008, 4:151-175.
32. Kotakadi V.S., Jin Y., Hofseth A.B., Ying L., Cui X., Volate S., Chumanevich A., Wood P.A., Price R.L., McNeal A., Singh U.P., Singh N.P., Nagarkatti M., Nagarkatti P.S., Matesic L.E., Auclair K., Wargovich M.J., Hofseth L.J. Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis. Carcinogenesis 2008, 29:1799-1806.
33. Lambert J.C., Grenier-Boley B., Chouraki V., Heath S., Zelenika D., Fievet N., Hannequin D., Pasquier F., Hanon O., Brice A., Epelbaum J., Berr C., Dartigues J.F., Tzourio C., Campion D., Lathrop M., Amouyel P. Implication of the immune system in Alzheimer's disease: evidence from genome-wide pathway analysis. J. Alzheimers Dis. 2010, 20:1107-1118.
34. Lautenschlager N.T., Ihl R., Müller W.E. Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective. Int. Psychogeriatr. 2012, 24:S46-S50.
35. Lee Y.W., Lin J.A., Chang C.C., Chen Y.H., Liu P.L., Lee A.W., Tsai J.C., Li C.Y., Tsai C.S., Chen T.L., Lin F.Y. Ginkgo biloba extract suppresses endotoxin-mediated monocyte activation by inhibiting nitric oxide- and tristetraprolin-mediated toll-like receptor 4 expression. J. Nutr. Biochem. 2011, 22:351-359.
36. Liu Y., Liu X., Hao W., Decker Y., Schomburg R., Fülöp L., Pasparakis M., Menger M.D., Fassbender K. IKKβ deficiency in myeloid cells ameliorates Alzheimer's disease-related symptoms and pathology. J. Neurosci. 2014, 34:12982-12999.
37. Liu S., Liu Y., Hao W., Wolf L., Kiliaan A.J., Penke B., Rübe C.E., Walter J., Heneka M.T., Hartmann T., Menger M.D., Fassbender K. TLR2 is a primary receptor for Alzheimer's amyloid β peptide to trigger neuroinflammatory activation. J. Immunol. 2012, 188:1098-1107.
38. Liu Y., Walter S., Stagi M., Cherny D., Letiembre M., Schulz-Schaeffer W., Heine H., Penke B., Neumann H., Fassbender K. LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide. Brain 2005, 128:1778-1789.
39. Lucin K.M., O'Brien C.E., Bieri G., Czirr E., Mosher K.I., Abbey R.J., Mastroeni D.F., Rogers J., Spencer B., Masliah E., Wyss-Coray T. Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer's disease. Neuron 2013, 79:873-886.
40. Luo Y., Smith J.V., Paramasivam V., Burdick A., Curry K.J., Buford J.P., Khan I., Netzer W.J., Xu H., Butko P. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:12197-12202.
41. Michaud J.P., Hallé M., Lampron A., Thériault P., Préfontaine P., Filali M., Tribout-Jover P., Lanteigne A.M., Jodoin R., Cluff C., Brichard V., Palmantier R., Pilorget A., Larocque D., Rivest S. Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:1941-1946.
42. Schroder K., Tschopp J. The inflammasomes. Cell 2010, 140:821-832.
43. Selkoe D.J. Alzheimer's disease is a synaptic failure. Science 2002, 298:789-791.
44. Shankar G.M., Li S., Mehta T.H., Garcia-Munoz A., Shepardson N.E., Smith I., Brett F.M., Farrell M.A., Rowan M.J., Lemere C.A., Regan C.M., Walsh D.M., Sabatini B.L., Selkoe D.J. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 2008, 14:837-842.
45. Shi C.S., Shenderov K., Huang N.N., Kabat J., Abu-Asab M., Fitzgerald K.A., Sher A., Kehrl J.H. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol. 2012, 13:255-263.
46. Smith J.V., Luo Y. Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761. J. Alzheimers Dis. 2003, 5:287-300.
47. Stackman R.W., Eckenstein F., Frei B., Kulhanek D., Nowlin J., Quinn J.F. Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment. Exp. Neurol. 2003, 184:510-520.
48. Tan M.S., Yu J.T., Tan C.C., Wang H.F., Meng X.F., Wang C., Jiang T., Zhu X.C., Tan L. Efficacy and adverse effects of Ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. J. Alzheimers Dis. 2015, 43:589-603.
49. Tchantchou F., Lacor P.N., Cao Z., Lao L., Hou Y., Cui C., Klein W.L., Luo Y. Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J. Alzheimers Dis. 2009, 18:787-798.
50. Tchantchou F., Xu Y., Wu Y., Christen Y., Luo Y. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease. FASEB J. 2007, 21:2400-2408.
51. Tian Y., Chang J.C., Greengard P., Flajolet M. The convergence of endosomal and autophagosomal pathways: implications for APP-CTF degradation. Autophagy 2014, 10:694-696.
52. Ude C., Schubert-Zsilavecz M., Wurglics M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin. Pharmacokinet. 2013, 52:727-749.
53. Vassar R., Citron M. Abeta-generating enzymes: recent advances in beta- and gamma-secretase research. Neuron 2000, 27:419-422.
54. Vellas B., Coley N., Ousset P.J., Berrut G., Dartigues J.F., Dubois B., Grandjean H., Pasquier F., Piette F., Robert P., Touchon J., Garnier P., Mathiex-Fortunet H., Andrieu S. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. 2012, 11:851-859. GuidAge Study Group.
55. Weinmann S., Roll S., Schwarzbach C., Vauth C., Willich S.N. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr. 2010, 10:14.
56. Wyss-Coray T., Rogers J. Inflammation in Alzheimer disease - a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med. 2012, 2:a006346.
57. Xie K., Liu Y., Hao W., Walter S., Penke B., Hartmann T., Schachner M., Fassbender K. Tenascin-C deficiency ameliorates Alzheimer's disease-related pathology in mice. Neurobiol. Aging 2013, 34:2389-2398.
58. Yao Z.X., Han Z., Drieu K., Papadopoulos V. Ginkgo biloba extract (EGb 761) inhibits beta-amyloid production by lowering free cholesterol levels. J. Nutr. Biochem. 2004, 15:749-756.
59. Yin B., Liang H., Chen Y., Chu K., Huang L., Fang L., Matro E., Jiang W., Luo B. EGB1212 post-treatment ameliorates hippocampal CA1 neuronal death and memory impairment induced by transient global cerebral ischemia/reperfusion. Am. J. Chin. Med. 2013, 41:1329-1341.
60. Zadoyan G., Rokitta D., Klement S., Dienel A., Hoerr R., Gramatté T., Fuhr U. Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: a cocktail interaction study in healthy volunteers. Eur. J. Clin. Pharmacol. 2012, 68:553-560.