祦եǾɤͳϷή䤹ǤϤʤ褦



ߥåؤ J. V. Smith ᡢ Y. Luo ˤ륤祦եΥӥ塼򤴾Ҳ𤷤ޤ礦


֥ ӥ ȥ饯 ( 祦ե ) ʬҳŪᥫ˥˴ؤ븦
Studies on molecular mechanisms of Ginkgo biloba extract Appl Microbiol Biotechnol (2004) 64: 465472 J. V. Smith . Y. Luo




祦եˤϣĤʬꡢ餬ˡѤäƤȤȤ餳Υӥ塼ϻϤޤ롣


1)ƥڥ


2)եܥΥ



1)ƥڥϼʬव롣


a)󥳥饤 ABCJM


b)ӥХ饤



a)󥳥饤ɤθ


󥳥饤ɤϷ쾮ij (PAF) Υ󥿥˥Ȥǡ쾮ijӶŽ˳롣ˤäƷս۴Ĥ ס1


󥿥˥ȤȤϤѤ˳ʪ (ɹʪ)


Ĥޤꥮ󥳥饤ɤϷηɤȤԤǤ롣



2)եܥΥɤθ


եܥΥɤϹѤȯ롣

եܥΥɤ˧ĤŷˤäƹƤ롣ˤäơҥɥ饸ˤȿ䤹ľŪ٥󥸺Ѥͭ (2)


ҥɥ饸ϥե꡼饸롣


ҥɥ饸¾ʪȿ䤹ѥģΣĤ롣


˥塼ʪǤ˰»ûФƤ⡢Υ饸뤬᡼Ϳ롣


եܥΥɤϤĤޤ˥塼뤳ȤԤǤ롣





SOD ( superoxide dismutase ) Τ褦ʹѥȯ륿Τ褦ʹʪä (3)(4)


SODȤФΥҥɥ饸̵ǤΤȡ


ȤSODϲȼƤޤ


եܥΥɤSODä롣




եܥΥɾο prooxidant transitional metal ions (㤨Fe2+) ȷ礷ƥ졼ȴĤ (3)


ˤ꿷ʥҥɥ饸˳ (2)(5)


ŴϻӤ䤹


ŴǤƱǤ


嵭ϡեܥΥɤŴȿƻɤȤ






ǤϤʬޤ।祦եμפʸ̤ˤĤơ



ե꡼饸롢ȥ쥹ˤĤ


ե꡼饸륹٥󥸥㡼ѤäƤ

ROS ( reactive oxygen species ) ȿǻ٤򸺾 (6)(7)(8)


ROS ( Ǽ ) Ȥϥե꡼饸롢ǤΡ


祦եϤ򸺤餹ȤϹѤˤĤƤ



ȿ (6)


ȿȤϡλϢȤݤΤȡ


뤭äǿǤȴ줿ϡե꡼饸Ȳ


줬ϢλϤޤꡣ


饸벽¾ʪŻҤå饸䤷Ƥ椯


饸ϷʻοǤĤĤ̤


Ȥ褦ˡȿȤϡлӲݡ


ƥ祦եϤϢȿƯͭ롣


ʤߤˡ


ӥߥE饸򸵤᤹ʪ


ӥߥŤΥץݼ¿̤ˤʤ䤹ä夲ͤʤΤդɬס


λɤΥץȤ֤ʤ顢եܥΥɤɤǤ礦




2 ȥ쥹


PBR ( peripheral-type benzodiazepine receptor ) ȯ򸺤餹 (6)


PBRȤϡ٥󥾥ԥΤΤȤǥιˤΤΤȡ


¿¸ߤƤ롣


祦եϥ̤򸺤餹褦Ǥ롣



¸ԲķʥۥǤϤΤΡΤ͡ʾ㳲ۥǤ⤢롣


ȤХȯʤȥ쥹ϡϤѽ̤ͤޤ󡣳ϤΥ˥塼󤬻ǤƤޤ


ϤˤϥμΤ¿ޤ


ʢ¿ơ饹ȥ쥹ϤҤȤ餻롣Ϥޤ̤ʵˡ


ϤΤΥȥ쥹ȿؤȡָƤӤ״ﴱǤ뤿ᡢ̤ΩĻȤߤǤ


ʥϡŪʥȥ쥹ϡ˳ϤΥ˥塼ֶʳפؤɤߤͤޤ


ֶʳפȤݤϥ˥塼󤬻ǤȤߤΤҤȤĤǤ


˻ɷ㤵줿˥塼˥륷।̤ή˥塼󤬶ʳ֤Ȥʤꡢư򵯤̤ơǤ롢Ȥݡ


ϤεǽˤĤϤΤȻפޤǰΤᡣ


Ϥϵ夵국Ƥӵꤹ뵭ﴱǤ


ޤϤΤΥȥ쥹ȿؤž륹åǤ⤢롣


äƳϤͤǤäƤ˥塼󤬿ľꡣ




ǾΥΥߥ ( MAO ) 㲼 (9)


MAO ( Υߥ󥪥 ) ˳ǾΥɡѥߥǻ٤夲롣


MAO˳ϡꥫǤϹĺޤȤƤȤ뤳Ȥޤ


줹ʤ祦եιĺѤ򼨤Ǥ




3 ˥塼Υݥȡؤκ


˥塼Υݥȡθ (10)(11)(12


ݥȡȤϥץव줿˦λǡ˦μȸ븽ݤǡ˥塼ǸΤҤȤġ




4 ǧεǽؤθ


祦եϥߥɥ١Ȥ𤵤Ƥޤ


в˦˦ˤ륢ߥɥ١ζŽ (11)


ջ׷ǽϤưʪˤ뿷νȥ쥹ؤα䵤ʬѲȤäҤФͭ (9)(13)


ģΣ»۾ʥΥѥ뤳Ȥޤ


ȤǾˤƤϡѥ¤βǡ衢¦ޤꤿޤ٤ʬˤभФȤʤ뤳Ȥޤ


۾ʥѥƱ֤夷ȲƤ椯


βϥߥɥ١ȸƤФޤ


ߥɥ١ϥĥϥޡ¤θΤҤȤĤȤ⸫Ƥޤ


ߥɥ١夷˥塼Ϥ䤬ƿ夷Ǥ뤳ȤʬäƤޤ


祦եϤοʳˤ˥塼Ȥ⤢ޤ


嵭ϥ祦եߥɥ١ηȤǤ


ʤߤˤΥӥ塼ˡ祦եεϲѤ𤹤ʸΰѤϤޤ󤬡βǽ򼨤ʸ򸫤Ĥ뤳ȤϤǤޤ


ʬҥ٥ǤϡȤ NDMAΡĹ˴طΡˤΥΥåȥޥ˥祦եͿϤä𤵤Ƥޤ




5 աήɤؤκ


쾮ij PAF ̤ˤǾβ (10)


ͳд˰ EDRF (Stimulation of endothelium-derivedrelaxing factor) λɷˤư̮̮Ӻٴɤν۴IJ (14)


ɤΤäȤ¦¸ߤ͡ʪʬ礷ޤ


EDRF (NO ) ⤽ΤΤҤȤġ


ǤϷɤдˤ롣


祦եήɤȤΤϤΤȹͤ롣




5 ãʪؤκ


ǾΦ1-ɥʥΡ5-HT1A ( ȥ˥ ) ΤӥॹΤǯˤ븺ͽ (6)


Ϥιȥ󥹥ݡμߤ (6)


ʥץ˦Ф줿륳ϡʥץ˦μΤȤǡ®ʬ򤵤ޤ 󥨥ƥ顼ˤäƥȿݻˡ


ʥץϿã򤹤뤿˥륳١ͭʤФʤޤ


˥塼ϥ륳θǤ륳ޤΤǡʬ򤵤ƼϤɺ򡢺١ʥץ˼ꤳɬפޤ


Ϥιȥ󥹥ݡȤϡ饳μ߸ΤȤǤ


Ĥޤꥤ祦եϥ륳䤹褦ǤʥΥꥵΨ夵ˡʤʤߤ˹ͻˤ⤳Ưޤ


륳ϡηؽư̲˴طãʪǤ뤳ȤϤΤȻפޤ




7 ȥ쥹ѡȯؤκѤʤ


ϤΥ륳ɼΤΥ쥮졼˳ (6)


祦եϡȥ쥹ؤϤȤ


ϤΥ륳ɼΤθ򤯤ȤȤκѤϡιƱͤƯ


륳ɼΤȤϥμΤǤ


μΤγȤϡΤΥȥ쥹ȿؤڤؤ뤿˽ס


ϤˤϥμΤ¿ꡢ椨ʥϳϤ˲ȤΤۤɤΤä




ΰҤž̤Ĵ᤹롣η̡˦ι֤äȥ쥹򶯲ã륳̤(15)


DNA佤˦ˤ뵡ǽ˴ؤ륿ѥѲ˱ƶ򤢤DNA»(15)


祦եϰȯ˺ѤϤζ˥塼˶Ưͭ롣




8 ¾


ߥȥɥꥢθƵĴΨäˤATP٥ (1)


ϥ祦եΥͥ륮䤹Ȥ


ۤˤ⡢祦եϹ⻳¤ͭǤȤ⤢롣


줬̣ΤϻǤμ߸Ψ夲ȤȤǤ


ΤʤǤǤμߤθ֤ϤӤޤ


椹Ȥ錄ϸƵۤĤ˺줬


椷ʤФʤʤȤˤϡ祦եݤޤ礦










椹ŻXSmall












ɺѤǾ㳲Фݸ (16)


Фβĵؤαƶ (6)(3)


祦եϼä˥塼褦Ǥ롣






ǤϡɤΤ褦ʥ祦եݤɤΤǤ礦


祦ե˴ޤޤ륮󥴡ϥˤɤʤȤϾΤȻפޤ


ȤϤ󥴡̤Υ祦ե򶡵뤹븶᡼ʤơ餯¸³ǤʤۤɡνϼǤ


祦եʼϤüˤϰʤȹͤƤɤ⤷ޤ


ȤϤƤθ᡼ϡ¤륤祦եͭͭʬ̤İƤޤ


ˤʤϥץȥ᡼䤤碌Ƥߤ뤳ȤɤǤ礦


ǤϡɤΥ祦եݤ뤫षƬǾΤϥ祦եΥݥƥ󥷥ɤФȤȤǤ礦


祦ե¾ΥץȤɤȤ߹碌ƻȤޤ礦


錄᤹ΤϡȤйͻۥե륻Ȥ߹碌뤳ȤǤ


ͻϥ祦եƱֶ͡ʳפޤƯ륳䤹ƯԤǤޤ


祦եȤ߹碌¸ǤϡADHD⤵Ƥޤ


Ϥ뤳ȤԤǤޤ



˥祦եȥۥե륻Ȥ߹碌ˤϡϡϤ뤳Ȥ⤵Ƥޤ


饵ץȤ̤˹ʬ˹礦祦եå򸫤ĤƤߤƤϤǤ礦





SWITCH ˤϡȤۤƱ̤Υ祦եͻۥե륻󡢥Хѥ˥饨۹礵Ƥޤ


祦եñȤݤȡޡȥץSWITCHȤ٤ƤߤƤ򤤤⤷ޤ

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References
(1)Defeudis FV (2002a) Bilobalide and Neuroprotection. Pharmacol

Res 46:565568

(2)Zimmermann M, Colciaghi F, Cattabeni F, Di Luca M (2002)Ginkgo biloba extract: from molecular mechanisms to the
treatment of Alzheimer's disease. Cell Mol Biol 48:613623

(3)Gohil K, Packer L (2002) Global gene expression analysis identifiescell and tissue specific actions of Ginkgo biloba extract, EGb761. Cell Mol Biol 48:625631

(4)Oken B, Storzbach D, Kaye J (1998) The efficacy of Ginkgo bilobaon cognitive function in Alzheimer disease. Arch Neurol55:14091415

(5)Ni Y, Zhao B, Hou J, Xin W (1996) Preventive effect of Ginkgobiloba extract on apoptosis in rat cerebellar neuronal cellsinduced by hydroxyl radicals. Neurosci Lett 214:115118

(6)DeFeudis F, Drieu K (2000) Ginkgo biloba extract (EGb 761) andCNS functions: basic studies and clinical applications. CurrDrug Targets 1:2558

(7)Lien E, Ren S, Bui H, Wang R (1999) Quantitative structure-activityrelationship analysis of phenolic antioxidants. Free Radic BiolMed 26:285294

(8)Smith J, Luo Y (2003) Elevation of oxidative free radicals inAlzheimer's disease models can be attenuated by Ginkgo bilobaextract EGb 761. J Alzheimer's Dis 5:287300

(9)Pardon M, Joubert C, Perez-Diaz F, Christen Y, Launay J, Cohen-Salmon C (2000) In vivo regulation of cerebral monoamineoxidase activity in senescent controls and chronically stressedmice by long-term treatment with Ginkgo biloba extract (EGb761) Mech Ageing Dev 113:15768

(10)Bastianetto S, Ramassamy C, Dore S, Christen Y, Poirier J, QuirionR (2000) The Ginkgo biloba extract (EGb 761) protectshippocampal neurons against cell death induced by betaamyloid.Eur J Neurosci 12:18821890

(11)Luo Y, Smith J, Paramasivam V, Burdick A, Curry K, Buford J,Khan I, Netzer W, Xu H, Butko P (2002) Inhibition of amyloidbetaaggregation and caspase-3 activation by the Ginkgo bilobaextract EGb761. Proc Natl Acad Sci USA 99:1219712202

DeFeudis FV (1998) Ginkgo biloba extract (EGb 761): fromchemistry to clinic. Ullstein, Weisbaden, Germany

(12)Smith J, Burdick A, Golik P, Khan I, Wallace D, Luo Y (2002) Antiapoptoticproperties of Ginkgo biloba extract EGb 761 indifferentiated PC12 cells. Cell Mol Biol 48:699707

(13)Cohen-Salmon C, Venault P, Martin B, Raffalli-Sebille M, BarkatsM, Clostre F, Pardon M, Christen Y, Chapouthier G (1997)Effects of Ginkgo biloba extract (EGb 761) on learning andpossible actions on aging. J Physiol 91:291300

(14)Smith P, Maclennan K, Darlington C (1996) The neuroprotectiveproperties of the Ginkgo biloba leaf: a review of the possiblerelationship to platelet-activating factor (PAF) J Ethnopharmacol50:131139

(15)DeFeudis FV (2002b) Effects of Ginkgo biloba extract (EGb 761)on gene expression: possible relevance to neurologicaldisorders and age-associated cognitive impairment. Drug DevRes 57:214235

(16)Oberpichler H, Sauer D, Rossberg C, Mennel HD, Krieglstein J(1990) PAF antagonist ginkgolide B reduces postischemicneuronal damage in rat brain hippocampus. J Cereb Blood FlowMetab 10:133135