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Anti-aging traditional Chinese medicine: potential mechanisms involving AMPK pathway and calorie restriction based on “medicine-food homology” theory

从“药食同源”探讨抗衰老中药激活AMPK通路改善能量代谢的潜在机制



全 文 :2016
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Vol41,No.6 March,2016
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,Tel:18565552084,Email:liudy209@163com
AntiagingtraditionalChinesemedicine:potentialmechanismsinvolvingAMPK
pathwayandcalorierestrictionbasedon"medicinefoodhomology"theory
LIUDongyan1,3,LIYihan1,3,XUYantong2,3,ZHUYan2,3
(1.TianjinUniversityofScience&Technology,Tianjin300457,China;
2.TianjinStateKeyLaboratoryofModernChineseMedicine,TianjinUniversityofTraditional
ChineseMedicine,Tianjin300457,China;3.CenterforResearchandDevelopmentofChineseMedicine,
TianjinInternationalJointAcademyofBiotechnology&Medicine,Tianjin300457,China)
[Abstract] TherehavebeenmanyreportsabouttheantiagingefectoftraditionalChinesemedicine(TCM),butthematerialbasis
andmechanismofactionhavenotbeenclearlyelucidatedAMPactivatedproteinkinase(AMPK)isthereceptorofenergymetabolism
anditslifeextendingefecthasbeenconfirmedindiferentexperimentsOverexpressionoractivationwithmetforminofAAK2/
AMPKhasbeenshowntoextendlifeexpectancyinnematodesandDrosophilaThepossibledownstreampathwaysofAMPKagainstag
ingincludeTOR/S6kpathway,FOXOspathwayandCRTCpathwayOneofthecoreconceptsoftraditionalChinesemedicineisdis
easeprevention,forwhichoneofmanifestationsistoimprovethebodywiththesamesourceofmedicineandfoodtoachievelongevity
·4411·
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AMPK
@NÐÑÒöP¶ƒÓ²fù
ItispossibletoactivateAMPKtoachievethegoalofhealthpreservationandprolongingthelifebysomeofthe"medicinefoodharmo
ny"treatmentsOursurveyfindsthatin"medicinefoodharmony"compoundTCM,"invigoratingthekidneydeficiencyandpromoting
bloodcirculation"classdominatesandSalviaeMiltiorhizaeRadixRhizoma,AstragaliRadix,CoptidisRhizoma,Poria,Atractylodes
MacrocephalaeRhizoma,RadixetRhizomaRhei,andGinsengRadixetRhizomaareusedinhighfrequencyNetworkpharmacology
analysisusingingenuitypathwayanalysis(IPA)softwarerevealedthatTCMderiveddrugsinteractingwithAMPKtargetproteinsin
cludedberberine,emodin,curcumin,resveratrol,alcohol,cordyceps,arctin,suggestinginacertainextentthefeasibilityof"medi
cinefoodhomology"drugstoextendthelifespanthroughtheAMPKpathwayOurstudycombinesacomprehensivedatabasequeryand
anIPAnetworkpharmacologyanalysistoidentifyChinesemedicinemonomerandcomponentsthatmayactivateAMPKpathwaytodelay
agingandtodiscussthepotentialofthesemedicinebyimprovingenergymetabolismtodelaytheagingprocess,basedontheconceptof
traditionalChinesemedicine"medicinefoodhomology"
[Keywords] AMPactivatedproteinkinase(AMPK);aging;traditionalChinesemedicine;calorierestriction
doi:10.4268/cjcmm20160629
  
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Ò@òµ¶Äŋ´P¶ƒ>Më\ËÄ
ÅÒö)¹Ýß

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[6]。
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Ñ :ì[?±>Lš=‹ƒ0£ý²

à
B[αå_FÔ、[βêëFÔ¨[γêëFÔ。™
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9ƒd’]
(Thr172)


ñXèƒÕ]_é“Òӕ–
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[78]。
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²Èí
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AAK2
œìÎXÈ퉊

,¯
œì²ïöû͋ŒÛZr5xÒöíC
ùƒ‚Ä
[914]。

AMPKα2ç÷:ˆP¶‡d,` 9rɓúΨ‰
Š
[15]。
†ð²­

¾.8àbPƒÌÍd/‹œÒ@ò:
TQÇì’S¡»¢<±‰Š
[1617]。
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–¡ï5­
SHR
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µu
10%。
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SHR
‡ˆ$

8àb
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128%,54%。
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ҕ
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­<±
‰ŠDB[vhi

2= dƒé


AMPK
³Æ°ƒ<
‰‚Ä`£DB•i.±–

8W¨eŽz.±–bê
AMPK
ÜÝBþ°pÄQƒ‰Š
[13]。
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AMPK
ƒ<Ć²W¨¨ŽzbÜÝ
AMPK
ƒ<Ä

[14]。
AMPK
• _ b O @ N Ö ü é u
liverkinaseB1
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¨
calcium/calmodulindependentkinasekinaseb
(CaMKKb)[19]
ҕ

6²ÒöÙÚÛ
,LKB1
é
AMPK
Öüƒ
ÒÓ
[20]。AMPK
eÎÏÖü@ò
TOR/S6k
èé
、FOXOs
è
é
、CRTC
èéöë
[21]。
111 TOR/S6k
èé
 
„…ãÿ

±ù
TOR
@Nœì<±
Èí

ÄQö‰Š
[22]。TOR
éd’]

Ғ]Ñ ÒÓ

‰
°ÕW¯ŽÊ

ÒÓ²ôÒÓÑ üÓ

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TOR
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AMPK
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TOR
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ƒ‚

ÖüB

?€£
:①AMPKÕ]_ҕ TSC2(tuber
oussclerosisprotein2),
—êZr±ù
TORC1
ƒhi
;②
·5411·
2016
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41
áà

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Vol41,No.6 March,2016
AMPK
Õ]_6è±ù
TORC1。
1,
,TORC1
ƒÛOÑ 
S6K
ґÎX
AMPKα2
(Ser491)
Õ]_

/±ù
Thr172
ƒÕ]_

Õ1

±ù
TORC1
ґ˜r[™š•_
AMPK[21]。
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èé
 FOXOs
é
Forkheadbox
á\Õ3

“
Η±‰Öü@òêëÛOçÔÕë

µi
RNAi
()^
ªþÛOÔÕð~

5£°‹ƒ°ŠÖ0
10%~20%。
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,FOXOs
üÓêøu±ù
Ins/IGF1(reduced
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ü
Ó
[23],
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èé
 
M{]óä~Œ<=Ñ á\aÒ
•Õ3
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ulatedtranscriptionalcoactivators(CRTCs)
é!u‚Pƒ
CREB
aҕÕ3
,¯
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CREB
çB


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CREB
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3”ÒöÝß

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ö

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CRTCs
†
AMPK
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[25]。
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AMPK
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,CRTC1(
Èí
CRTC
ü
Ӑ

ÁëI_®Ø

ê^ª
CRTC1
b
AMPK
çèҒ
]
S76
†
S179
~

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CRTC1
Ë•_®Ø

µu
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ëP]¥¨,”„…ò

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-p)‹´Ô䆑3fù

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(traditionalChinesemedicine,TCM)
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1‘„…Pò¯œÒé@òЯÒ
öP¶ì—nƒ
[26]。
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AMPK
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j
”,
ҕ
AMPK
ґÎXfÆ°5xÒöíCùƒ®
Ø

ê1‘$,Ñґҕ
AMPK。
Õ1

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AMPK
ҕ
™š

­eÎÏ$,—n×Ò
,`
­“,ͤ>œn–—n‘
›

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1。
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p)²­{‚ƒ„…€;

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•
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ì
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²
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Jr^Þ
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öP+”~œi^Þ
25
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ditionalChinesemedicine
2 
ҕ
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ƒ€$,

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ҕ
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)

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,`
b3‘{‚

ù+ú­Ò•
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Eyì

B˜˜$,B
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më1‘$,•‘e—Ò‘Zrҕ
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u<Ü
2。
Ü

pÿ

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pÿ3~œ˜ñd
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ҕ
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ؗêêøÒöP¶<*ÎÏ

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Nƒ$,€

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@NÐÑÒöP¶ƒÓ²fù
  
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1 
ҕ
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@N€$,
Table1 CompoundtraditionalChinesemedicinescapableofAMPKactivation
€ • *Ë^Þ
Å%Î Ëj

 )

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Ëï

D3

m*

‡Ë


[27]
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‡Ë

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9w
[28]
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æ^

hFË

y*

RS

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Ù_‹


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[29]
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m*

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Ëï

 )

ü×
[30]
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2、
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jk3

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[32]
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i)

m
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ù
)、
Ùno

RS

«Å

Ëð

¶Ã

pœq

T
)、
m
*

íî



FèK
[3334]
îÅ©rš½ °FË

Ùoz

°s™*

RS

m*

Ëðö
[35]
€A_€ Ÿ£

Ÿ¥

šÔË



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[3637]
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Ëð

\3

ù
)、
̐

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)、
ė

Ë»
2、
9w



™*


[38]
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Áù
)、
z<

Ùt3

ô

9w

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u3


)、
ɱ

vw

¢{ª

ã[
[39]
-#úë_ƀ RS

pœq

£K

 )

Ùx

å{
[40]
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Ëï

Ë»

D3
[41]
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cy

vh

m*

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[42]
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z<
[43]
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wz

$n

á{

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î[

z[

ù
)、
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m
)、
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[44]
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å{

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m*

$n
[45]
×j€ Ëð

Ëj

×ÚÌ
[4647]
Ü
2 
ҕ
AMPK
—8,eB‚‘
Table2 TraditionalChinesemedicinederivedsinglecomponentscapableofAMPKactivation
d_ _=‹ hi *Ë^Þ
>Åd Ëj>Å p
STZ
æçƒ

­ÅÆ¢:ˆ%í
AMPKαÕ]_ [4849]
°‹ºd ËðO •_
AMPK,
Η
L6
‡ˆŽÄÅÅíq
[50]
vhi @ò
AMPKNFκBv<@N±ùBV2:F´ÄÅΆ–ÄÅÕ3ÔÕÜÝ [51]
ôº ÎX
AMPK
Õ]_ҕ

±ù
ACC
•–

ÐїO&e
[52]
Žd €‚3Ž Η
STZ
æçƒ

­ÅÆ¢:ˆ%톎z
AMPK
Õ]_
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