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Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2012, Article ID 191632, 13 pagesdoi:10.1155/2012/191632
Review Article
Chinese Medicine in Diabetic Peripheral Neuropathy:Experimental Research on Nerve Repair and Regeneration
Yuanlin Piao and Xiaochun Liang
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical Collegeand Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China
Correspondence should be addressed to Xiaochun Liang, [email protected]
Received 11 February 2012; Revised 8 April 2012; Accepted 26 April 2012
Academic Editor: Monica Rosa Loizzo
Copyright © 2012 Y. Piao and X. Liang. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.
Diabetic peripheral neuropathy (DPN) is one of the most common complications of chronic diabetes mellitus. Pathologicalcharacteristics of DPN include axonal atrophy, nerve demyelination, and delayed regeneration of peripheral sensory nerve fibers.The goal of treatment in DPN is not only to ameliorate neurological symptoms but also to slow or reverse the underlyingneurodegenerative process. Schwann cells and neurotrophic factors play important roles in the repair and regeneration ofperipheral nerves. The present paper reviews current studies and evidence regarding the neurological effects of traditional Chinesemedicine, with an emphasis on recent developments in the area of nerve repair and regeneration in DPN.
1. Introduction
Diabetic peripheral neuropathy (DPN) is a common com-plication of chronic diabetes. Pathological characteristicsof DPN include axonal atrophy, nerve demyelination, anddelayed regeneration of peripheral sensory nerve fibers. Toour knowledge, the pathophysiological mechanism of DPNin dysfunctional peripheral nerve repair and regeneration isnot well understood.
The symptoms associated with DPN have been men-tioned in various traditional Chinese medicine (TCM)references. Pujifang (Prescriptions for Universal Relief), anancient Chinese medicine book written in the Ming dynasty,described the following constellation of symptoms: “Thekidney pattern of diabetes consists of symptoms of thirst,dry eye, impotence, and annoying pain in the hands andfeet.” Moreover, in Wangxugaoyian (Medical Records ofWangxugao) from the Qing dynasty, there was a case of apatient with diabetes noted to have “numbness of handsand feet” and “limbs as cold as ice.” The differentiation ofDPN implicates the domains of “sinew impediment,” “bloodimpediment,” and “leg flaccidity” in Chinese medicine [1].
From the viewpoint of TCM [1], the etiology andpathogenesis of DPN are as follows: (1) with an increased
duration of disease in diabetes, a deficiency of yin burnsbody fluid and blood, resulting in empty heat. This increasesblood viscosity, resulting in blood stasis, as well as blockageof sinews and channels; (2) excessive intake of foods highin fat and sugar content results in the deficiency of spleenand stomach, resulting in the accumulation of dampnessand phlegm, which has a synergistic effect with stasis; (3)sinew and channels demonstrate poor nourishment becauseof the deficiency of liver and kidney; (4) the deficiency ofyin results in a deficiency of yang, which generates an innercold that results in microvascular coagulation. These fouraspects result in a decreased peripheral flow of qi and bloodto muscles, sinew, and channels. With regard to visceralorgan systems, DPN is related to the liver, spleen, and kidney.The nature of DPN is deficiency secondarily complicatedby excess; the deficiency is the root, and the excess is asubsequent manifestation. The root cause is deficiency inqi, yin, and yang; the subsequent complication is bloodstasis and phlegm accumulation. Common patterns andtreatments of DPN are summarized in Table 1.
Recently the effects of Schwann cells and neurotrophicfactors on the repair and regeneration of peripheral nervehave been of research interest. Recent studies have shownthat TCM medications may affect neuronal repair and
2 Evidence-Based Complementary and Alternative Medicine
Ta
ble
1:C
omm
onpa
tter
ns
and
trea
tmen
tsof
DP
Nin
Ch
ines
em
edic
ine.
Patt
ern
Clin
ical
man
ifes
tati
onT
her
apeu
tic
prin
cipl
eTr
eatm
ent
(for
mu
la)
Ori
gin
offo
rmu
laC
omp
onen
ts
Defi
cien
cyof
Yin
and
bloo
dst
asis
Nu
mbn
ess
and
burn
ing
pain
inh
ands
and
feet
grad
ual
lyex
ten
dsto
the
enti
relim
bs,
aggr
avat
edat
nig
ht;
nig
ht
swea
tin
g;sp
onta
neo
us
swea
tin
g;h
eat
sen
sati
onin
the
ches
t,pa
lms
and
sole
s;so
ren
ess
and
wea
knes
sof
the
lum
bar
regi
onan
dkn
ees
join
ts,d
rym
outh
;th
irst
y;dr
yst
ool;
dark
-red
ton
gue
wit
hpe
eled
orlit
tle
coat
ing;
fin
ean
dch
oppy
puls
e.
Nou
rish
Yin
and
rem
ove
bloo
dst
asis
Zh
ibai
Dih
uan
gW
an1
(An
emar
rhen
a-P
hel
lode
ndr
on-R
ehm
ann
iaP
ill)
toge
ther
wit
hTa
ohon
gsiw
uta
ng
2(P
ersi
ca-C
arth
amu
sFo
ur
Subs
tan
ces
Dec
octi
on)
1Ji
ngu
iyao
lue
(Syn
opsi
sof
Pre
scri
ptio
ns
ofth
eG
olde
nC
ham
ber)
;2Y
izon
gjin
jian
(Gol
den
Mir
ror
ofM
edic
ine)
Shud
ihua
ng(R
adix
Reh
man
nia
epr
epar
ata)
,Sh
anzh
uyu
(Fru
ctu
sC
orn
i),S
hany
ao(R
hiz
oma
Dio
scor
eae)
,Zex
ie(R
hiz
oma
Alis
mat
is),
Fulin
g(P
oria
),M
udan
pi(C
orte
xM
outa
n),
Zhi
mu
(Rh
izom
aA
nem
arrh
enae
),H
uang
bai(
Cor
tex
Ph
ello
den
dri)
,Dan
ggui
(Rad
ixA
nge
licae
sin
ensi
s),
Chu
anxi
ong
(Rh
izom
aC
hu
anxi
ong)
,Bai
shao
(Rad
ixPa
eon
iae
alba
),Ta
oren
(Sem
enPe
rsic
ae),
Hon
ghua
(Flo
sC
arth
amit
inct
orii
)
Defi
cien
cyof
Yan
gan
dbl
ood
stas
is
Nu
mbn
ess
pain
,agg
rava
ted
atn
igh
tor
enco
un
ters
cold
nes
s,av
ersi
onto
cold
,col
dlim
bs,s
oren
ess
and
wea
knes
sof
the
lum
bar
regi
onan
dkn
ees
join
ts,t
aste
less
nes
sin
the
mou
thw
ith
out
thir
sty,
impo
ten
ce,
prem
atu
reej
acu
lati
on,p
oor
orlo
ose
stoo
l,pa
leor
dark
ton
gue,
wh
ite
thic
kor
grea
syco
atin
g,de
epfi
ne
orde
epsl
owpu
lse.
War
man
dto
nif
yYa
ng
and
rem
ove
bloo
dst
asis
Jin
guis
hen
qiw
an1
(Gol
den
Ch
est
Kid
ney
-QiP
ill)
toge
ther
wit
hTa
ohon
gsiw
uta
ng
2(P
ersi
ca-C
arth
amu
sFo
ur
Subs
tan
ces
Dec
octi
on)
1Ji
ngu
iyao
lue
(Syn
opsi
sof
Pre
scri
ptio
ns
ofth
eG
olde
nC
ham
ber)
;2Y
izon
gjin
jian
(Gol
den
Mir
ror
ofM
edic
ine)
Fuzi
(Rad
ixA
con
itil
ater
alis
prep
arat
a),G
uizh
i(R
amu
lus
Cin
nam
omi)
,Sha
nzhu
yu(F
ruct
us
Cor
ni)
,Sh
anya
o(R
hiz
oma
Dio
scor
eae)
,Zex
ie(R
hiz
oma
Alis
mat
is),
Mud
anpi
(Cor
tex
Mou
tan
),Fu
ling
(Por
ia),
Shud
ihua
ng(R
adix
Reh
man
nia
epr
epar
ata)
,D
angg
ui(R
adix
An
gelic
aesi
nen
sis)
,Chu
anxi
ong
(Rh
izom
aC
hu
anxi
ong)
,Bai
shao
(Rad
ixPa
eon
iae
Alb
a),T
aore
n(S
emen
Pers
icae
),H
ongh
ua(F
los
Car
tham
itin
ctor
ii)
Evidence-Based Complementary and Alternative Medicine 3
Ta
ble
1:C
onti
nu
ed.
Patt
ern
Clin
ical
man
ifes
tati
onT
her
apeu
tic
prin
cipl
eTr
eatm
ent
(for
mu
la)
Ori
gin
offo
rmu
laC
omp
onen
ts
Defi
cien
cyof
Yin
turn
ing
into
win
d
Nu
mbn
ess
orso
ren
ess
inh
ands
and
feet
,di
zzin
ess,
and
vert
igo
and
afe
elin
gof
falli
ng,
sore
nes
s,an
dw
eakn
ess
ofth
elu
mba
rre
gion
and
knee
join
ts,h
eat
sen
sati
onin
the
ches
t,pa
lms
and
sole
s;st
agge
rin
gga
it,r
edto
ngu
ew
ith
peel
edco
atin
g,de
epfi
ne,
and
wir
ypu
lse.
Nou
rish
Yin
and
exti
ngu
ish
win
d
Yig
uan
jian
1(O
ne
Lin
kin
gD
ecoc
tion
)to
geth
erw
ith
Zh
enga
nxi
fen
gtan
g2
(Pac
ifyi
ng
the
Live
ran
dE
xtin
guis
hin
gW
ind
Dec
octi
on)
1Li
uzh
ouyi
hua
(Med
ical
Talk
sof
Liu
zhou
);2
Yix
-u
ezh
ongz
hon
gcan
xilu
(Med
ical
Rec
ords
Loya
lto
Ch
ines
eM
edic
ine
and
Ref
eren
ceto
Wes
tern
Med
icin
e)
Shas
hen
(Rad
ixG
leh
nia
e),M
aido
ng(R
adix
Oph
iopo
gon
is),
Dan
ggui
(Rad
ixA
nge
licae
sin
ensi
s),
Shen
gdih
uang
(Rad
ixR
ehm
ann
iae)
,Gou
qi(F
ruct
us
Lyci
ich
inen
sis)
,Niu
xi(R
adix
Ach
yran
this
bide
nta
tae)
,Dai
zhes
hi(H
aem
atit
um
)Lo
nggu
(Mas
todi
Oss
isfo
ssili
a),M
uli(
Con
cha
Ost
reae
),G
uiba
n(P
last
rum
Test
udi
nis
),X
uans
hen
(Rad
ixSc
roph
ula
riae
),T
ianm
endo
ng(R
adix
Asp
arag
i),
Bai
shao
(Rad
ixPa
eon
iae
alba
),Y
inch
enha
o(H
erba
Art
emis
iae
scop
aria
e),C
huan
lianz
i(Fr
uct
us
Toos
enda
n),
Mai
ya(F
ruct
us
Hor
deig
erm
inat
us)
,G
anca
o(R
adix
Gly
cyrr
hiz
aeu
rale
nsi
s)
Ph
legm
and
bloo
dst
asis
bloc
kin
gth
ech
ann
els
Nu
mbn
ess,
pare
sth
esia
,ave
rsio
nto
cold
orh
eat,
sore
nes
san
dw
eakn
ess
ofth
elu
mba
rre
gion
and
knee
sjo
ints
,afe
elin
gof
hea
vin
ess
inlo
wer
limbs
,mu
scle
atro
phy,
epig
astr
icfu
llnes
s,lo
ssof
appe
tite
,poo
ror
loos
est
ool,
noc
turn
alem
issi
on,i
mpo
ten
ceor
prem
atu
reej
acu
lati
on,s
wol
len
ton
gue
wit
hth
ick
grea
syco
atin
g,de
ep-fi
ne
orde
ep-c
hop
pypu
lse.
Dis
pelp
hle
gman
dre
mov
ebl
ood
stas
is
Pis
hen
shu
angb
uwan
1(S
plee
n-K
idn
eyD
oubl
eSu
pple
men
tP
ill),
Erc
hen
tan
g2
(Tw
oO
ldD
ecoc
tion
)an
dTa
ohon
gsiw
uta
ng
3(P
ersi
ca-C
arth
amu
sFo
ur
Subs
tan
ces
Dec
octi
on)
1X
ian
xin
gzh
aiyi
x-u
egu
angb
iji(E
xten
sive
Med
ical
Not
esof
Ear
lyA
wak
eH
ouse
);2
Taip
-in
ghu
imin
hej
ijufa
ng
(Pre
scri
ptio
ns
from
the
Gre
atPe
ace
Imp
eria
lGra
ceP
har
mac
y);3
Leiz
hen
gzh
icai
(Cla
ssifi
edPa
tter
ns
wit
hC
lear
-cu
tTr
eatm
ents
)
Ren
shen
(Rad
ixG
inse
ng)
,Lia
nzi(
Sem
enN
elu
mbi
nis
),Tu
sizi
(Sem
enC
usc
uta
e),W
uwei
zi(F
ruct
us
Sch
isan
drae
),Sh
anzh
uyu
(Fru
ctu
sC
orn
i),
Shan
yao
(Rh
izom
aD
iosc
orea
e),C
heqi
anzi
(Sem
enP
lan
tagi
nis
),R
oudo
ukou
(Sem
enM
yris
tica
e),J
uhon
g(E
xoca
rpiu
mC
itri
rubr
um
),Sh
aren
(Fru
ctu
sA
mom
i),B
ajit
ian
(Rad
ixM
orin
dae
offici
nal
is),
Bug
uzhi
(Fru
ctu
sPs
oral
eae)
,Ban
xia
(Rh
izom
aP
inel
liae
prep
arat
um
),C
henp
i(Pe
rica
rpiu
mC
itri
reti
cula
tae)
,Ful
ing
(Por
ia),
Zhi
ganc
ao(R
adix
Gly
cyrr
hiz
aepr
epar
ata)
,Shu
dihu
ang
(Rad
ixR
ehm
ann
iae
prep
arat
a),D
angg
ui(R
adix
An
gelic
aesi
nen
sis)
,Chu
anxi
ong
(Rh
izom
aC
hu
anxi
ong)
,B
aish
ao(R
adix
Paeo
nia
eal
ba),
Taor
en(S
emen
Pers
icae
),H
ongh
ua(F
los
Car
tham
itin
ctor
ii)
4 Evidence-Based Complementary and Alternative Medicine
regeneration in DPN. In this paper, we examine currentexperimental research in Chinese literature and discuss thepossible mechanisms of action of TCM on DPN, focusingon its effects on Schwann cells and neurotrophic factors(Table 2).
The literature search was conducted in the followingdatabase: China Journals Full-Text Database (2002–2012)(http://dlib.cnki.net/kns50/index.aspx). The keywords usedwere: nerve repair, nerve regeneration, Chinese medicine,acupuncture, sciatic nerve, diabetic rats, Schwann cell,neurotrophic factors, and diabetic neuropathy. The authorsread full articles and reached consensus after discussion.The effects and mechanisms of Chinese medicine on nerverepair and regeneration were reviewed. Articles includedin the study covered the following domains of TCM: (1)Chinese herbal medicine therapy and (2) acupuncture andmoxibustion. Research of monomers, review articles, andabstracts were excluded. A total of 21 peer-reviewed paperswritten in Chinese were included in this paper.
2. Schwann Cells
Schwann cells are glial cells of the peripheral nerve system.They are important for maintaining the microenvironmentfor regeneration of peripheral nerves. Schwann cells not onlysupport the repair of peripheral nerves, but they also induce,stimulate, and modulate axonal regeneration and myelinformation via expression and secretion of multiple proteins,peptides, and other bioactive substances. Thus, Schwann cellsplay an important role in promoting repair and regenerationafter peripheral nerve injury. In hyperglycemia, a series ofchanges, including abnormal expression of proteins andenzymes, result in increased apoptosis and decreased cellproliferation and repair signals [23, 24]. Therefore, inhibit-ing apoptosis and promoting growth of Schwann cells maybe crucial in the prevention and treatment of DPN.
2.1. Chinese Medicine Promotes Schwann Cell Prolifera-tion. Multiple studies have demonstrated the presence ofaxonal degeneration and peripheral nerve demyelinationin DPN. Characteristic histopathological findings includelipid droplets, Reich granules, and glycogen granules in thecytoplasm of Schwann cells, mitochondrial swelling, anddisappearance of mitochondrial cristae, which are indicativeof a proapoptotic state. Schwann cell proliferation andmigration promote nerve regeneration and thus are likelyto mitigate in DPN. Sun et al. [2] applied the serumpharmacological method (Figure 1) to investigate the effectof serum containing Jinmaitong on the proliferation ofSchwann cells cultured under hyperglycemic conditions.Compared with a control group treated with neurotrophin,there was no significant difference between the two groups intheir effect on enhancing the proliferation of Schwann cells.Furthermore, both groups also increased the expression ofnerve growth factor (NGF) in the same cultured Schwanncells. Wu et al. [3] used the XTT method and the 3H2TdRincorporation assay to assess the activity and proliferation ofSchwann cells isolated from sciatic nerve tissues of newbornWistar rats. They confirmed that allyl glycosides significantly
Chinese medicine
Serum containing Chinese medicine
Cultured Schwann cells
+
Figure 1: Preparation of serum containing Chinese medicine.
reversed the inhibition of proliferation of Schwann cellsinduced by hyperglycemia.
2.2. Chinese Medicine Inhibits Apoptosis of Schwann Cells.Apoptosis is a manifestation of cell damage. The typicalhistopathological pattern of mitochondrial swelling anddissolved mitochondrial cristae occur in response tostreptozotocin (STZ) administered to diabetic rats [25]. Invitro experiments showed that hyperglycemia reproducesthis pattern of apoptosis in Schwann cells [26]. Ji et al. [4]reported that application of Jiangtangshuluofang normalizedlevels of serum insulin and glycosylated hemoglobin andinhibited the apoptosis of Schwann cells surroundingsciatic nerves in diabetic rats. The mechanism is thoughtto be related to the inhibition of proapoptotic factorscaspase-3 and Bax and promoting of expression of Bcl-2, anantiapoptotic factor. Liu et al. [5] reported that the Chinesemedicines astragalus, salvia, and yam have antiapoptoticactions on Schwann cells cultured under hyperglycemicconditions. These medicines increased levels of Bcl-2 expres-sion, while inhibiting expression of caspase-3. Furthermore,the combination of those three herbs was synergistic. Invitro studies showed that the medicated serum containingJinmaitong decreased the expression of inducible nitric oxidesynthase (iNOS), NADPH oxidase p22-phox, 8-OHdG, andactive caspase-3 (17 kDA) in Schwann cells, suggestingthat Jinmaitong can reduce oxidative injury and apoptosisassociated with hyperglycemic conditions (Table 3) [6, 7].
3. Chinese Medicine’s Effects onNeurotrophic Factors
Neurotrophic factors are essential for the maintenance andsurvival of neurons. When peripheral nerve are injured,neurotrophic factors can bond to specific tyrosine kinasereceptors on the surface of target cells, preventing neuronalcell death and promoting the repair of neurons and axonregeneration. Neurotrophic factors can be classified into:neurotrophins (including NGF, brain-derived neurotrophicfactor, and neurotrophin); neuropoietic cytokines (including
Evidence-Based Complementary and Alternative Medicine 5
Ta
ble
2:K
eyda
tafr
omci
ted
stu
dies
inC
hin
ese
liter
atu
re.
Firs
tau
thor
(yea
r)re
f.T
issu
e/ce
llsE
xper
imen
talt
reat
men
tC
ontr
oltr
eatm
ent
Met
hod
sfo
rm
ain
indi
cato
rsM
ain
outc
omes
Au
thor
’sco
ncl
usi
on
Sun
(200
9)[2
]Sc
hwan
nce
lls
Seru
mco
nta
inin
gJi
nm
aito
ng
(Sin
ew-C
han
nel
Un
obst
ruct
ion
)
Neu
rotr
opin
MT
Tas
say
for
prol
ifer
atio
nof
Schw
ann
cells
Pro
mot
edpr
olif
erat
ion
ofSc
hwan
nce
llsan
din
crea
sed
expr
essi
onof
NG
Fof
Schw
ann
cells
cult
ure
din
hig
hgl
uco
se
“Can
prom
ote
the
prol
ifer
atio
nof
Schw
ann
cells
and
incr
ease
the
expr
essi
onof
NG
Fof
Schw
ann
cells
cult
ure
din
hig
hgl
uco
se”
Wu
(200
9)[3
]Sc
hwan
nce
llsA
llylg
lyco
side
extr
acte
dfr
omH
erba
Rh
odio
lae
Shen
mai
zhu
shey
e(G
inse
ng-
Oph
iopo
gon
isin
ject
ion
)
XT
Tm
eth
odan
d3H
-TdR
inco
rpor
ativ
em
eth
odfo
rac
tivi
tyan
dpr
olif
erat
ive
capa
bilit
yof
Schw
ann
cells
,res
pec
tive
ly
Impr
oved
prol
ifer
ativ
eca
pabi
lity
ofSc
hwan
nce
lls
“Can
impr
ove
inh
ibit
ory
effec
ton
prol
ifer
ativ
eca
pabi
lity
ofSc
hwan
nce
llin
hig
hgl
uco
sem
ilieu
,in
vitr
o”
Ji(2
009)
[4]
Scia
tic
ner
ve
Jian
gtan
gshu
luof
ang
(Dec
reas
eG
luco
seFr
eeC
olla
tera
lsP
resc
ript
ion
)fo
r8
W
Met
hyco
bala
nd
Glic
lazi
de
Rad
ioim
mu
noa
ssay
for
insu
linle
vel
and
HbA
1c;t
un
elfo
rap
opto
sis;
imm
un
ohis
toch
emic
alm
eth
odfo
rex
pres
sion
ofB
cl-2
,Bax
,an
dca
spas
e-3
Incr
ease
dB
cl-2
expr
essi
on;r
edu
ced
casp
ase-
3an
dB
axex
pres
sion
;de
crea
sed
apop
tosi
sof
Schw
ann
cells
.
“Can
incr
ease
the
insu
linle
vela
nd
low
erH
bA1c
leve
lin
diab
etic
rats
,in
hib
itSc
hwan
nce
llsap
opto
sis;
the
mec
han
ism
mig
ht
bere
late
dto
its
inh
ibit
ion
ofca
spas
e-3
and
Bax
expr
essi
on,a
nd
prom
otin
gth
eex
pres
sion
ofB
cl-2
”
Liu
(201
0)[5
]Sc
hwan
nce
lls
Hu
angq
i(R
adix
Ast
raga
li),D
ansh
en(R
adix
Salv
iae
milt
iorr
hiz
ae),
Shan
yao
(Rh
izom
aD
iosc
orea
e),
and
com
pou
nds
ofth
ree
her
balm
edic
ines
Non
e
Flow
cyto
met
erfo
rap
opto
sis
rate
ofSc
hwan
nce
lls;r
eal-
tim
eP
CR
for
expr
essi
onof
Bcl
-2an
dca
spas
e-3
mR
NA
;Wes
tern
blot
tin
gfo
rex
pres
sion
ofB
cl-2
and
casp
ase-
3pr
otei
n
Dec
reas
edap
opto
sis
rate
;in
crea
sed
Bcl
-2m
RN
Aan
dpr
otei
nex
pres
sion
;dec
reas
edca
spas
e-3
mR
NA
expr
essi
onin
astr
agal
us,
salv
iaan
dco
mpo
un
dgr
oups
;de
crea
sed
expr
essi
onof
casp
ase-
3pr
otei
nin
astr
agal
us,
yam
,an
dco
mpo
un
dgr
oups
.
“Th
eap
opto
sis
ofSc
hwan
nce
llco
-cu
ltu
red
wit
hen
doth
elia
lcel
lin
hig
hgl
uco
seca
nbe
prot
ecte
dby
Ch
ines
eh
erbs
,diff
eren
th
erbs
hav
edi
ffer
ent
effec
t,th
eco
mpo
un
din
terv
enti
ongr
oup
was
the
best
”
Zh
ao(2
011)
[6]
Schw
ann
cells
Seru
mco
nta
inin
gJi
nm
aito
ng
(Sin
ew-C
han
nel
Un
obst
ruct
ion
)
Vit
amin
C
Imm
un
oflu
ores
cen
cem
eth
odfo
rth
eex
pres
sion
ofiN
OS;
real
-tim
efl
uor
esce
nce
quan
tita
tive
PC
Rfo
rp2
2-ph
oxm
RN
Aex
pres
sion
Dec
ease
dex
pres
sion
ofiN
OS
and
p22-
phox
mR
NA
ofSc
hwan
nce
lls
“Can
dow
n-r
egu
late
the
expr
essi
onof
iNO
Spr
otei
nof
NA
DP
Hox
idat
ive
p22-
phox
subu
nit
mR
NA
ofSc
hwan
nce
llscu
ltu
red
inh
igh
ergl
uco
sem
ediu
m”
Pia
o(2
011)
[7]
Schw
ann
cells
Seru
mco
nta
inin
gJi
nm
aito
ng
(Sin
ew-C
han
nel
Un
obst
ruct
ion
)
Vit
amin
C
En
zym
e-lin
ked
imm
un
oabs
orba
nt
assa
yfo
r8-
OH
dGle
vel;
imm
un
oflu
ores
cen
cefo
rex
pres
sion
ofca
spas
e-3
prot
ein
;rea
l-ti
me
flu
ores
cen
cequ
anti
tati
veP
CR
for
expr
essi
onof
casp
ase-
3m
RN
A
Dec
reas
ed8-
OH
dGle
vel;
decr
ease
dex
pres
sion
ofca
spas
e-3
prot
ein
and
mR
NA
inth
esu
pern
atan
tof
Schw
ann
cells
“Can
impr
ove
hig
h-g
luco
sein
duce
dox
idat
ive
inju
ryof
DN
Aap
opto
sis
inSc
hwan
nce
lls,s
ugg
esti
ng
itm
igh
tim
prov
eox
idat
ive
inju
ryan
dap
opto
sis
indi
abet
icn
euro
path
y”
6 Evidence-Based Complementary and Alternative MedicineT
abl
e2:
Con
tin
ued
.
Firs
tau
thor
(yea
r)re
f.T
issu
e/ce
llsE
xper
imen
talt
reat
men
tC
ontr
oltr
eatm
ent
Met
hod
sfo
rm
ain
indi
cato
rsM
ain
outc
omes
Au
thor
’sco
ncl
usi
on
Qu
(200
8)[8
]Sc
iati
cn
erve
Jin
mai
ton
g(S
inew
-Ch
ann
elU
nob
stru
ctio
n)
for
16W
Neu
rotr
opin
Rea
l-ti
me
flu
ores
cen
cequ
anti
tati
veP
CR
for
NG
Fm
RN
Aof
scia
tic
ner
ve;i
mm
un
ohis
toch
emic
alm
eth
odfo
rN
GF
prot
ein
ofsc
iati
cn
erve
Incr
ease
dN
GF
and
NG
Fm
RN
Ain
scia
tic
ner
ve.
“Can
upr
egu
late
the
expr
essi
onof
NG
Fpr
otei
nan
dN
GF
mR
NA
insc
iati
cn
erve
ofra
tsw
ith
DP
N”
Den
g(2
007)
[9]
Scia
tic
ner
ve
Qit
engt
ongl
uoy
in(A
stra
galu
sV
ine
Free
Col
late
rals
Dec
octi
on)
for
6W
Non
eIm
mu
noh
isto
chem
ical
assa
yfo
rex
pres
sion
ofN
GF
and
subs
tan
ceP
insc
iati
cn
erve
Impr
oved
chan
ges
ofsc
iati
cn
erve
,in
crea
sed
expr
essi
onof
NG
Fan
dsu
bsta
nce
Pin
scia
tic
ner
ve
“Has
the
prev
enti
vean
dtr
eatm
ent
effec
tson
path
olog
ical
chan
ges
ofsc
iati
cn
erve
ofD
PN
rats
.It’s
poss
ible
mec
han
ism
may
beas
soci
ated
wit
hth
epr
omot
ion
ofex
pres
sion
ofen
doge
nou
sN
GF
and
subs
tan
ceP
”
Yu(2
004)
[10]
Scia
tic
ner
veTa
ngm
onin
g(G
luco
seE
nd
Peac
eG
ran
ule
s)fo
r6
WM
ethy
coba
lR
ever
setr
ansc
ript
ion
PC
Rfo
rN
GF
mR
NA
ofsc
iati
cn
erve
Incr
ease
dex
pres
sion
ofN
GF
mR
NA
“App
ears
tou
preg
ula
teth
eex
pres
sion
ofN
GF
mR
NA
ofsc
iati
cn
erve
indi
abet
icra
ts”
Xu
(200
9)[1
1]Sc
iati
cn
erve
,se
rum
Yiq
iton
glu
ofaz
ufa
ng
(Ton
ify
QiF
ree
Col
late
rals
Pre
scri
ptio
n)
for
6W
Met
hyco
bal
ELI
SAfo
rse
rum
NG
FIn
crea
sed
NO
,dec
reas
edM
DA
,an
din
crea
sed
NG
F;im
prov
edh
isto
path
olog
ical
chan
ges
“Can
prev
ent
DP
Nvi
aim
prov
emen
tof
MD
A,N
O,a
nd
NG
F”
Wan
g(2
010)
[12]
Scia
tic
ner
veTa
ngb
ikan
g(S
uga
rB
lock
age
Rec
over
y)fo
r8
WM
ethy
coba
l
Rea
l-ti
me
flu
ores
cen
cequ
anti
tati
veP
CR
for
NG
Fm
RN
Aof
scia
tic
ner
ve;E
LISA
for
NG
Fle
veli
nse
rum
Incr
ease
dN
GF
leve
lin
seru
man
din
crea
sed
NG
Fm
RN
Aex
pres
sion
.
“Can
incr
ease
the
NG
Fpr
otei
nan
dm
RN
Aex
pres
sion
topl
ayan
impo
rtan
tro
leof
peri
pher
aln
erve
prot
ecti
on”
Ma
(200
7)[1
3]Sc
iati
cn
erve
Mor
us
alba
extr
act
for
8W
Met
hyco
bal
Path
olog
ical
obse
rvat
ion
for
expr
essi
onof
NG
Fan
dm
yelin
basi
cpr
otei
n
Incr
ease
dex
pres
sion
ofN
GF
and
mye
linba
sic
prot
ein
insc
iati
cn
erve
“Mor
us
alba
extr
act
has
fun
ctio
ns
ofin
crea
sin
gth
eex
pres
sion
ofN
GF
and
mye
linba
sic
prot
ein
thu
sim
prov
ing
the
DP
N”
Don
g(2
007)
[14]
Scia
tic
ner
ve
Shen
shu
(BL
23),
Zus
anli
(ST
36);
G68
05-I
Iel
ectr
oacu
pun
ctu
rede
vice
,con
tin
uou
sw
ave,
freq
uen
cy2
Hz,
20m
inev
ery
othe
rda
y,fo
r12
tim
es
Met
hyco
bal
Imm
un
ity
and
flu
ores
cen
tqu
anti
tati
onP
CR
for
NG
Fm
RN
A,
and
imm
un
ohis
toch
emic
alst
ain
ing
anal
ysis
for
NG
Fpr
otei
n-p
osit
ive
cells
ofsc
iati
cn
erve
Incr
ease
dex
pres
sion
ofN
GF
prot
ein
and
NG
Fm
RN
Ain
scia
tic
ner
ve.
“Can
upr
egu
late
the
expr
essi
onof
NG
Fpr
otei
nan
dN
GF
mR
NA
,an
dpr
omot
esc
iati
cn
erve
repa
irin
DP
Nra
ts”
Hu
ang
(201
0)[1
5]Sc
iati
cn
erve
Posi
tive
elec
trod
elo
cate
d1.
0cm
abov
eth
ein
teri
orof
prox
imal
grea
ter
troc
han
ter,
dist
alfi
bula
rh
ead
and
the
insi
deof
each
0.3
cm.
Nee
dle
0.5
cmin
dept
h,
wit
hth
est
imu
lus
inte
nsi
tyof
2-3
V,a
tth
efr
equ
ency
of10
0be
ats/
min
,45
min
each
day
Non
eR
ever
setr
ansc
ript
ase-
PC
Rfo
rex
pres
sion
ofN
GF
mR
NA
and
IGF-
1m
RN
Aof
scia
tic
ner
ve
From
2nd
wee
k,th
eex
pres
sion
ofN
GF
mR
NA
and
IGF-
1m
RN
Ain
crea
sed,
at10
thw
eek;
the
expr
essi
onof
NG
Fm
RN
Aan
dIG
F-1
mR
NA
sust
ain
edin
hig
her
leve
l.
“Can
elev
ate
the
mR
NA
expr
essi
onof
NG
Fan
dIG
F-1
insc
iati
cn
erve
ofdi
abet
icra
t,w
hic
hm
aybe
one
ofth
em
ech
anis
ms
ofac
upu
nct
ure
ondi
abet
icn
euro
path
y”
Evidence-Based Complementary and Alternative Medicine 7
Ta
ble
2:C
onti
nu
ed.
Firs
tau
thor
(yea
r)re
f.T
issu
e/ce
llsE
xper
imen
talt
reat
men
tC
ontr
oltr
eatm
ent
Met
hod
sfo
rm
ain
indi
cato
rsM
ain
outc
omes
Au
thor
’sco
ncl
usi
on
Yin
(200
8)[1
6]Sc
iati
cn
erve
Mox
aed
atth
epo
ints
ofY
ishu
(Ex-
B3)
and
Zus
anli
(ST
36),
15m
inea
chpo
int,
once
daily
for
56co
nse
cuti
veda
ys
Non
eN
euro
elec
trop
hysi
olog
ical
dete
ctio
nfo
rSN
CV
;ELI
SAfo
rN
GF
ofsc
iati
cn
erve
Dec
reas
edbl
ood
glu
cose
leve
l;in
crea
sed
SNC
V;i
ncr
ease
dN
GF
con
ten
tin
scia
tic
ner
ve.
“Th
eim
prov
ing
effec
tof
mox
ibu
stio
non
diab
etic
per
iph
eral
neu
rolo
gica
lsym
ptom
sin
ara
tm
odel
ofD
PN
may
bere
late
dto
anin
crea
sein
the
NG
Fco
nte
nt
and
prom
otio
nof
per
iph
eral
neu
ropr
otec
tion
”
Wan
g(2
010)
[17]
Scia
tic
ner
veJi
nm
aito
ng
(Sin
ew-C
han
nel
Un
obst
ruct
ion
)fo
r8
WN
euro
trop
in
Th
ehy
drot
her
mal
tail-
flic
kan
dpa
inth
resh
old
tom
ech
anic
alst
imu
lati
on;S
AB
Cim
mu
noh
isto
chem
istr
ym
eth
odfo
rC
NT
Fex
pres
sion
and
real
-tim
efl
uor
esce
nce
quan
tita
tive
PC
Rfo
rC
NT
Fm
RN
Aex
pres
sion
insc
iati
cn
erve
Th
epa
inth
resh
olds
wer
era
ised
and
tail-
flic
kla
ten
cies
wer
esh
orte
ned
;th
eex
pres
sion
ofC
NT
Fm
RN
Aan
dpr
otei
nw
asin
crea
sed
“Can
obvi
ousl
yu
preg
ula
teth
eex
pres
sion
ofC
NT
Fm
RN
Aan
dpr
otei
nin
the
scia
tic
ner
veof
rats
wit
hn
euro
path
y”
Wan
g(2
010)
[18]
Schw
ann
cells
Seru
mco
nta
inin
gJi
nm
aito
ng
(Sin
ew-C
han
nel
Un
obst
ruct
ion
)
Neu
rotr
opin
SAB
Cim
mu
noh
isto
chem
istr
ym
eth
odfo
rC
NT
Fex
pres
sion
and
real
-tim
efl
uor
esce
nce
quan
tita
tive
PC
Rfo
rC
NT
Fm
RN
Aex
pres
sion
inSc
hwan
nce
lls
Incr
ease
dC
NT
Fan
dC
NT
Fm
RN
Aex
pres
sion
inSc
hwan
nce
lls
“Can
upr
egu
late
the
expr
essi
onof
CN
TF
and
CN
TF
mR
NA
ofra
tSc
hwan
nce
llsin
cult
ure
dh
igh
glu
cose
med
ium
,so
asto
impr
ove
DP
N”
Zen
g(2
005)
[19]
Scia
tic
ner
ve
Xia
okel
ingn
ongs
uoy
e(D
iabe
tes
Agi
lity
Con
cen
trat
ion
Flu
id)
for
8W
Met
hyco
bal
Rel
ativ
equ
anti
tyP
CR
for
IGF
mR
NA
Incr
ease
dex
pres
sion
ofIG
F-1
mR
NA
insc
iati
cn
erve
“Is
invo
lved
inth
ere
gula
tion
ofIG
F-1
mR
NA
expr
essi
on,a
nd
prob
ably
prev
ents
diab
etic
peri
pher
aln
euro
path
yfr
omde
teri
orat
ion”
Xu
(200
9)[2
0]Sc
iati
cn
erve
Qin
gyin
gtan
g(C
lear
ing
Nu
trit
ive
QiD
ecoc
tion
)fo
r10
WM
ethy
coba
lE
LISA
for
IGF-
1in
seru
m;I
GF-
1in
scia
tic
ner
vean
dliv
erIn
crea
sed
IGF-
1le
veli
nse
rum
,liv
eran
dsc
iati
cn
erve
“In
crea
seth
eex
pres
sion
ofIG
F-1
inti
ssu
e,an
dh
ave
effec
tsof
ner
vere
pair
inD
NP
rats
”
Wan
g(2
010)
[21]
Scia
tic
ner
veTa
ngm
onin
g(G
luco
seE
nd
Peac
eG
ran
ule
s)fo
r8
WN
one
Wes
tern
blot
tin
gfo
rex
pres
sion
ofN
GF
and
IGF-
1in
scia
tic
ner
ve;
scia
tic
ult
rast
ruct
ure
obse
rvat
ion
bytr
ansm
issi
onel
ectr
onm
icro
scop
e
Incr
ease
dex
pres
sion
ofN
GF
and
IGF-
1;pa
thol
ogic
alch
ange
sof
scia
tic
ner
vew
ere
impr
oved
bytr
ansm
issi
onel
ectr
onm
icro
scop
e
“Has
som
epr
otec
tive
effec
ton
scia
tic
ner
vein
diab
etic
rats
.Th
em
ech
anis
mm
aybe
rela
ted
toth
eu
preg
ula
tion
ofth
eex
pres
sion
ofN
GF
and
IGF-
1pr
otei
ns.”
Zh
ang
(200
8)[2
2]Se
rum
Xia
oket
ongb
ikel
i(D
iabe
tes
Free
Obs
tru
ctio
nG
ran
ula
)M
ethy
coba
lR
adio
imm
un
oass
ayfo
rIL
-1β
and
TN
F-α
,ELI
SAfo
rC
D54
Red
uce
dth
ele
velo
fIL-
1β,T
NF-α
,an
dC
D54
“Can
relie
veor
impr
ove
diab
etic
peri
pher
aln
erve
inju
ryby
inte
rfer
ing
wit
hin
flam
mat
ion
fact
ors
indi
abet
es”
MT
T:m
ethy
lth
iazo
lylt
etra
zoliu
m;E
LIS
A:e
nzy
me-
linke
dim
mu
noa
bsor
ben
tas
say;
MD
A:m
alon
dial
dehy
de;D
PN
:dia
beti
cp
erip
her
aln
euro
path
y;ST
Z:s
trep
tozo
toci
n;N
GF:
ner
vegr
owth
fact
or;A
LL
:Allo
xan
;P
CR
:pol
ymer
ase
chai
nre
acti
on;C
NT
F:ci
liary
neu
rotr
oph
icfa
ctor
;SN
CV
:sen
sory
ner
veco
ndu
ctio
nve
loci
ty.
8 Evidence-Based Complementary and Alternative MedicineT
abl
e3:
Sum
mar
yof
form
ula
sci
ted
inth
isre
view
.
Firs
tau
thor
(yea
r)re
f.Fo
rmu
laTr
adit
ion
also
urc
eof
form
ula
Trad
itio
nal
indi
cati
onC
ompo
nen
tsFu
nct
ion
Rat
ion
ale
offo
rmu
la
Ji(2
009)
[4]
Jian
gtan
gshu
luof
ang
(Dec
reas
eG
luco
seFr
eeC
olla
tera
lsP
resc
ript
ion
)
Em
piri
calf
orm
ula
ofD
r.D
ash
un
Che
n
DP
N,p
atte
rnof
defi
cien
cyof
qian
dyi
n,fl
uid
defi
cien
cyh
eat
and
bloo
dst
asis
,de
fici
ency
ofbl
ood
turn
ing
into
win
d
Shen
gdih
uang
(Rad
ixR
ehm
ann
iae)
,Sh
anzh
uyu
(Fru
ctu
sC
orn
i),G
ouqi
zi(F
ruct
us
Lyci
i),G
egen
(Rad
ixP
uer
aria
e),H
uang
qi(R
adix
Ast
raga
li),D
ansh
en(R
adix
Salv
iae
milt
iorr
hiz
ae),
Puh
uang
(Pol
len
Typh
ae),
Shui
zhi(
Hir
udo
),H
uang
lian
(Rh
izom
aC
opti
dis)
,C
hant
ui(P
erio
stra
cum
Cic
adae
),Ji
li(F
ruct
us
Trib
uli)
Nou
rish
yin
ton
ify
qi,
clea
rh
eat
and
moi
sten
dryn
ess,
acti
vate
bloo
dan
dre
mov
est
asis
,dis
pel
win
dan
dfr
eeco
llate
rals
.
Ch
ief:
shen
gdih
uang
,sha
nzhu
yu,g
ouqi
zian
dge
gen
rege
nde
rfl
uid
and
clea
rh
eat,
nou
rish
yin
ofliv
er,k
idn
eyan
dlu
ng.
Dep
uty
:hua
ngqi
ton
ifies
qi;d
ansh
en,
puhu
ang
and
shui
zhir
emov
est
asis
and
free
colla
tera
ls.
Ass
ista
nt:
huan
glia
ncl
ears
hea
t;ch
antu
ian
djil
irel
ieve
itch
ing.
Pia
o(2
011)
[7]
Jin
mai
ton
g(S
inew
-Ch
ann
elU
nob
stru
ctio
n)
Em
piri
calf
orm
ula
ofD
r.X
iaoc
hun
Lian
g
DP
N,p
atte
rnof
kidn
eyde
fici
ency
and
bloo
dst
asis
;pat
tern
ofde
fici
ency
ofbo
thyi
nan
dya
ng,
inte
rior
cold
and
stas
is
Tusi
zi(S
emen
Cu
scu
tae)
,Nuz
henz
i(F
ruct
us
Lig
ust
rilu
cidi
),Sh
uizh
i(H
iru
do),
Yanh
usuo
(Rh
izom
aC
oryd
alis
),H
uan
gqi(
Rad
ixA
stra
gali)
,Sh
engd
ihu
ang
(Rad
ixR
ehm
ann
iae)
,Gui
zhi(
Ram
ulu
sC
inn
amom
i),X
ixin
(Her
baA
sari
)
Ton
ify
kidn
ey,
acti
vate
bloo
d,w
arm
and
un
bloc
kch
ann
els
and
vess
els.
Ch
ief:
tusi
zito
nifi
esya
ng
and
nou
rish
esyi
nof
kidn
ey,s
ecu
res
esse
nce
and
impr
oves
visi
on,a
nd
chec
ksdi
arrh
ea;
nuzh
enzi
nou
rish
esyi
nof
liver
and
kidn
ey,a
nd
clea
rsem
pty-
hea
t.D
epu
ty:s
huiz
hian
dya
nhus
uobr
eak
bloo
d,ex
pels
tasi
san
dre
lieve
pain
.A
ssis
tan
t:hu
angq
ian
dsh
engd
ihua
ngto
nif
yqi
and
nou
rish
yin
;gui
zhia
nd
xixi
nw
arm
and
un
bloc
kch
ann
els
and
vess
els,
and
prom
ote
qian
dbl
ood
circ
ula
tion
.
Den
g(2
007)
[9]
Qit
engt
ongl
uoy
in(A
stra
galu
sV
ine
Free
Col
latr
als
Dec
octi
on)
Em
piri
calf
orm
ula
DP
N,p
atte
rnof
qide
fici
ency
and
bloo
dst
asis
Hua
ngqi
(Rad
ixA
stra
gali)
,Hua
ngba
i(C
orte
xP
hel
lode
ndr
i),N
iuxi
(Rad
ixA
chyr
anth
isbi
den
tata
e),J
ixue
teng
(Cau
lisSp
ath
olob
i),C
angz
hu(R
hiz
oma
Atr
acty
lodi
s),Y
iyir
en(S
emen
Coi
cis)
,Qin
gdai
(In
digo
Nat
ura
lis)
Ton
ify
qi,a
ctiv
ate
bloo
dan
dre
mov
est
asis
.
Not
men
tion
edab
out
trad
itio
nal
rati
onal
e.T
he
auth
ors
stat
edth
at“B
ased
onm
oder
nph
arm
acol
ogic
alre
sear
ch.
Hua
ngqi
stre
ngt
hen
imm
un
ity;
jixue
teng
and
niux
imod
ula
tem
icro
-cir
cula
tion
;hu
angb
ai,c
angz
hu,n
iuxi
and
yiyi
ren
hav
efu
nct
ion
sof
regu
lati
ng
glu
cose
.”
Xu
(200
9)[1
1]
Yiq
iton
glu
ofaz
ufa
ng
(Ton
ify
QiF
ree
Col
late
rals
Pre
scri
ptio
n)
Em
piri
calf
orm
ula
DP
N,p
atte
rnof
kidn
eyde
fici
ency
,qi
defi
cien
cyan
dob
stru
ctio
nof
colla
tera
lves
sels
.
Shud
ihua
ng(R
adix
Reh
man
nia
epr
aepa
rata
),H
esho
uwu
(Rad
ixPo
lygo
nim
ult
iflor
i),L
uosh
iten
g(C
aulis
Trac
hel
osp
erm
i),H
uang
qi(R
adix
Ast
raga
li),D
ilong
(Lu
mbr
icu
s),W
ugon
g(S
colo
pen
dra)
,Q
uanx
ie(S
corp
io)
Nou
rish
yin
,ton
ify
kidn
eyan
dfr
eeco
llate
rals
Ch
ief:
shud
ihua
ngan
dhe
shou
wu
nou
rish
yin
and
ton
ify
kidn
ey.
Dep
uty
:luo
shit
eng
and
huan
gqit
onif
yqi
and
free
colla
tera
ls.
Ass
ista
nt:
dilo
ng,w
ugon
gan
dqu
anxi
efr
eeco
llate
rals
and
relie
vepa
in.
Wan
g(2
010)
[12]
Tan
gbik
ang
(Su
gar
Blo
ckag
eR
ecov
ery)
Ava
riat
ion
ofH
uan
gqig
uiz
hi-
Wuw
uta
ng
(Ast
raga
lus-
Cin
nam
omu
mFi
ve-I
ngr
edie
nt
Dec
octi
on)∗
Blo
odim
pedi
men
t,ex
hib
itin
gn
um
bnes
sse
nsa
tion
insk
inan
dlim
bs,s
ligh
tly
chop
pyan
dti
ght
puls
e.
Hua
ngqi
(Rad
ixA
stra
gali)
,Nuz
henz
i(F
ruct
us
Lig
ust
rilu
cidi
),G
uizh
i(R
amu
lus
Cin
nam
omi)
,Chi
shao
(Rad
ixPa
eon
iae
rubr
a),H
uang
qin
(Rad
ixSc
ute
llari
ae),
Hua
nglia
n(R
hiz
oma
Cop
tidi
s),S
huiz
hi(H
iru
do)
Ton
ify
qian
den
rich
yin
,det
oxif
yan
dre
solv
est
asis
.
Hua
ngqi
ton
ifies
qian
dst
ren
gth
ens
defe
nce
-ext
erio
r;gu
izhi
war
ms
the
chan
nel
san
dfr
eeya
ng;
nuzh
enzi
nou
rish
esyi
nof
liver
and
kidn
ey;c
hish
aodi
ssip
ates
stas
isan
dre
lieve
spa
in;
huan
gqin
and
huan
glia
ncl
ear
hea
t,dr
yda
mpn
ess
and
deto
xify
;shu
izhi
brea
ksbl
ood
and
expe
lsst
asis
.
Evidence-Based Complementary and Alternative Medicine 9
Ta
ble
3:C
onti
nu
ed.
Firs
tau
thor
(yea
r)re
f.Fo
rmu
laTr
adit
ion
also
urc
eof
form
ula
Trad
itio
nal
indi
cati
onC
ompo
nen
tsFu
nct
ion
Rat
ion
ale
offo
rmu
la
Zen
g(2
005)
[19]
Xia
okel
ingn
ongs
uoy
e(D
iabe
tes
Agi
lity
Con
cen
trat
ion
Flu
id)
Em
piri
calf
orm
ula
DP
N,p
atte
rnof
defi
cien
cyof
qian
dyi
nan
dbl
ood
stas
is
Sang
shen
(Fru
ctu
sM
ori)
,Sh
engd
ihua
ng(R
adix
Reh
man
nia
e),
Geg
en(R
adix
Pu
erar
iae)
,Hua
ngqi
(Rad
ixA
stra
gali)
,Ren
shen
(Rad
ixG
inse
ng)
,Xua
nshe
n(R
adix
Scro
phu
lari
ae),
Shui
zhi(
Hir
udo
)
Nou
rish
kidn
eyyi
n,
ton
ify
qian
dac
tiva
tebl
ood.
Ch
ief:
sang
shen
and
shen
gdih
uang
nou
rish
yin
and
ton
ify
kidn
ey.
Dep
uty
:xua
nshe
nan
dge
gen
nou
rish
yin
and
enge
nde
rfl
uid
.A
ssis
tan
t:hu
angq
ian
dre
nshe
n,to
nif
yqi
;sh
uizh
iis
assi
stan
t,ac
tiva
tebl
ood
and
rem
ove
stas
is.
Xu
(200
9)[2
0]
Qin
gyin
gtan
g(C
lear
ing
Nu
trit
ive
Qi
Dec
octi
on)
From
Wen
bin
gtia
obia
n(S
yste
mat
ized
Iden
tifi
cati
onof
War
mPa
thog
enD
isea
ses)
Hea
tin
the
nu
tien
tas
pect
patt
ern
,ex
hib
itin
gfe
ver
wh
ich
ish
igh
erat
nig
ht,
occa
sion
alde
liriu
m,
rest
less
nes
s,in
som
nia
,th
irst
orn
oth
irst
,ski
nra
shes
,dry
tou
nge
and
fin
era
pid
puls
e.
Shui
niuj
iao
(Cor
nu
Bu
bali)
,Sh
engd
ihua
ng(R
adix
Reh
man
nia
e),
Xua
nshe
n(R
adix
Scro
phu
lari
ae),
Zhu
ye(F
oliu
mP
hyllo
stac
hys
nig
rae)
,M
aido
ng(R
adix
Oph
iopo
gon
is),
Dan
shen
(Rad
ixSa
lvia
em
iltio
rrh
izae
),H
uang
lian
(Rh
izom
aC
opti
dis)
,Jin
yinh
ua(F
los
Lon
icer
ae),
Lian
qiao
(Fru
ctus
Fors
yth
iae)
Nou
rish
yin
and
disp
elh
eat
and
acti
vate
bloo
dan
dfr
eeth
ech
ann
els.
Ch
ief:
shui
niuj
iao
and
shen
gdih
uacl
ear
the
hea
tin
nu
trie
nt
aspe
ctan
dco
olth
ebl
ood.
Dep
uty
:xua
nshe
nan
dm
aido
ngn
ouri
shyi
nan
dcl
ear
hea
t.A
ssis
tan
t:jin
yinh
ua,l
ianq
iao,
huan
glia
nan
dzh
uye
clea
rh
eat
and
deto
xify
,pr
omot
eto
disp
elth
epa
thog
enfr
omn
utr
ien
tas
pect
toqi
aspe
ct;d
ansh
enac
tiva
tes
bloo
dan
ddi
spel
stas
isan
dh
eat.
Wan
g(2
010)
[21]
Tan
gmon
ing
(Glu
cose
En
dPe
ace
Gra
nu
les)
Em
piri
calf
orm
ula
DP
N,p
atte
rnof
qide
fici
ency
and
bloo
dst
asis
Hua
ngqi
(Rad
ixA
stra
gali)
,Yan
husu
o(R
hiz
oma
Cor
ydal
is),
Sanq
i(R
adix
Not
ogin
sen
g),C
hish
ao(R
adix
Paeo
nia
eru
bra)
,Dan
shen
(Rad
ixSa
lvia
em
iltio
rrh
izae
),C
huan
xion
g(R
hiz
oma
Ch
uan
xion
g),H
ongh
ua(F
los
Car
tham
i),S
umu
(Lig
nu
mSa
ppan
),Ji
xuet
eng
(Cau
lisSp
ath
olob
i)
Ton
ify
qi,a
ctiv
ate
bloo
d,fr
eeco
llate
rals
and
relie
vepa
in.
Ch
ief:
huan
gqit
onifi
esqi
and
prom
otes
bloo
dci
rcu
lati
on.
Dep
uty
:yan
husu
oan
dch
uanx
iong
rem
ove
stas
isan
dre
gen
der
fres
hbl
ood.
Ass
ista
nt:
sanq
irem
oves
stas
isan
dre
lieve
pain
;dan
shen
,hon
ghua
and
jixue
teng
rem
ove
stas
isan
dfr
eeco
llate
rals
.
Zh
ang
(200
8)[2
2]
Xia
oket
ongb
i(D
iabe
tes
Free
Obs
tru
ctio
nG
ran
ula
)
Em
piri
calf
orm
ula
ofD
r.R
ongf
aZ
han
g
DP
N,p
atte
rnof
defi
cien
cyof
qian
dyi
nan
dbl
ood
stas
is
Hua
ngqi
(Rad
ixA
stra
gali)
,Dan
ggui
(Rad
ixA
nge
licae
sin
ensi
s),G
egen
(Rad
ixP
uer
aria
e),W
eilin
gxia
n(R
adix
Cle
mat
idis
),Z
ushi
ma
(Cor
tex
Dap
hn
egi
rald
ii),
Sang
baip
i(C
orte
xM
ori)
Ton
ify
qi,a
ctiv
ate
bloo
dan
dre
mov
est
asis
,fre
ech
ann
els
and
relie
vepa
in.
Ch
ief:
huan
gqi,
dang
guia
nd
gege
nto
nif
yqi
,act
ivat
ebl
ood
and
relie
vepa
in.
Dep
uty
:wei
lingx
ian
and
zush
ima
disp
elw
ind
and
relie
vepa
in.
Ass
ista
nt:
sang
baip
icle
ars
lun
gh
eat.
∗fr
omJi
ngu
iyao
lue
(Syn
opsi
sof
Pre
scri
ptio
ns
ofth
eG
olde
nC
ham
ber)
,wh
ich
ingr
edie
nts
are
huan
gqi(
Rad
ixA
stra
gali)
,gui
zhi(
Ram
ulu
sC
inn
amom
i),s
haoy
ao(R
adix
Paeo
nia
e),s
heng
jiang
(Rh
izom
aZ
ingi
beri
sre
cen
s)an
dda
zao
(Fru
ctu
sJu
juba
e).
10 Evidence-Based Complementary and Alternative Medicine
ciliary neurotrophic factor [CNTF] and interleukins); andthe transforming growth factor-beta (TGF-β) superfamily(which can be subdivided into acidic fibroblast growthfactors and basic fibroblast growth factors). In addition, thereare other neurotrophic factors, such as insulinlike growthfactor (IGF) and glial-derived neurotrophic factor [27].Present studies suggest that diabetes-induced dysfunction ofnerve regeneration results partially from decreased levels ofsome neurotrophic factors or their receptors.
3.1. NGF. NGF was the first discovered and most typicalneurotrophic factor. It plays an important role in neuronaldevelopment, differentiation, and the maintenance of nor-mal functions. NGF not only protects neurons and reducestheir degeneration and death, but it also promotes nerveregeneration after nerve injury. There is a deficiency of NGFin diabetes, and reduced levels or activity of NGF plays asignificant role in the pathogenesis of diabetic neuropathy[28]. Qu et al. [8] observed that 12 weeks after the successof a STZ-induced diabetic neuropathy rat model, comparedwith the normal rats, the tail-flick latency was significantlyprolonged, the pain threshold was significantly lower, andNGF protein and mRNA expression in the sciatic nerve weresignificantly reduced in the model rats. Moreover, NGF-mRNA expression level in the sciatic nerve was negativelycorrelated with the tail-flick latency and was positively cor-related with the mechanical pain threshold in the model rats.The model rats were orally administered with the Chinesemedicine compound Jinmaitong in three different dosagegroups: large, medium, and small. After the intervention, themedium-dosage group of Jinmaitong showed that the tail-flick latency was significantly reduced, the pain thresholdsignificantly increased, and sciatic NGF-mRNA and proteinexpression were significantly increased, compared with themodel control group. Furthermore, in vitro study provedthat the serum containing Jinmaitong promotes secretionof NGF in high-glucose cultured Schwann cells [2]. Dengand Zhang [9] investigated the effects of Qitengtongluoyinon protein expression of NGF and neuropeptide substanceP (SP) in sciatic nerves of STZ-induced diabetic multipleneuropathy rats, and proved that Qitengtongluoyin canprevent and treat sciatic neuropathy in STZ-induced dia-betic multiple neuropathy rats, probably via promoting theexpression of NGF and SP protein. Yu et al. [10] reported thata 6-week intervention of the Chinese medicine compoundTangmoning in STZ-induced diabetic rats resulted in asignificant increase of NGF mRNA and that the effect wassimilar to that of methycobal. Xu and Yang [11] reported thatYishentongluofazufang can increase the NGF content in theserum of STZ-induced rats. Wang and Liu [12] proved thatTangbikang can increase serum NGF level and increase theexpression of NGF mRNA of sciatic nerve in diabetic rats. Maet al. [13] testified in their experimental study that certainextracts of morus alba can improve diabetic peripheralneuropathy in alloxan-induced diabetic rats, via promotingexpression of NGF and myelin protein in sciatic nerves.
Besides the above-mentioned Chinese herbal medicinestudies, recent studies have shown that acupuncture andmoxibustion can improve DPN, possibly via their effects on
NGF. Dong et al. [14] conducted electroacupuncture (EA) onthe points of Shenshu (BL 23) and Zusanli (ST 36) in STZ-induced diabetic rats. After the intervention was done 12times, the EA group showed increased NGF-positive cells andincreased NGF mRNA expression in sciatic nerve, comparedwith the model group, suggesting EA upregulates expressionof protein and mRNA of NGF and improves nerve repair inDPN. Huang et al. [15] found that EA treatment of diabeticrats resulted in increased expression of NGF mRNA in thesciatic nerve. Yin et al. [16] applied moxibustion on STZ-induced diabetic rats, moxaed at the points of Yishu (Ex-B3) and Zusanli (ST 36), 15 min each point, once daily for56 consecutive days, found that blood glucose significantlydecreased, nerve conduction velocity significantly increased,and NGF content significantly increased in treatment group,compared with those in model group, suggesting thatmoxibustion has functions of peripheral nerve protectionwhich may be related to its promotion of NGF expressionof nerve.
3.2. CNTF. CNTF has multiple biological activities: pro-moting survival of neurons and protecting motor neurons;inhibiting degeneration of axons of motor nerves; enhanc-ing growth speed of axon; preventing muscle atrophy. Inaddition, administration of CNTF results in promotingregeneration of peripheral nerves [29]. CNTF protein andbioactivity are reduced in the peripheral nerve of diabeticrats, and CNTF treatment improved nerve regeneration andprevented nerve-conduction slowing in diabetic rats, sug-gesting CNTF plays an important role in nerve regenerationin DPN [30]. Wang et al. [17] observed the Chinese medicinecompound Jinmaitong’s effects on CNTF expression indiabetic neuropathy rats, and confirmed that Jinmaitongcan upregulate the expression of the protein and mRNA ofCNTF in the sciatic nerves of diabetic neuropathy rats. Forin vitro study, Wang et al. [18] prepared drug-containingserums with the application of 15 times the adult dosage ofboth Jinmaitong and neurotrophin and grouped as the blankcontrol group (no cells added), normal control group (addedwith normal rat serum), high-glucose group (added withglucose), Jinmaitong group (added with serum containingJinmaitong and normal rat serum), and neurotropin group(added with serum containing neurotropin). Except forthe blank control group and normal control group, the50 mmol/L glucose was added to all the groups to achievehigh-glucose Schwann cell models. The expression of CNTFand CNTF mRNA was detected by SABC immunohisto-chemistry method and real-time fluorogenetic quantitativePCR, respectively. Results showed that compared withthe normal control group, the CNTF and CNTF mRNAexpression in the high-glucose group, Jinmaitong group, andneurotropin group were lowered. Compared with the high-glucose group, the CNTF and CNTF mRNA expression ofthe Jinmaitong group and neurotropin group were increased,and the CNTF mRNA expression in the Jinmaitong groupwas higher than that in the neurotropin group. This suggeststhat Jinmaitong upregulates the expression of CNTF andCNTF mRNA of Schwann cells cultured in high-glucosemedium.
Evidence-Based Complementary and Alternative Medicine 11
Chinese medicine
Apoptosis Proliferation
Schwann cells
Caspase-3iNOSNADPH oxidase
Bcl-2 NGF CNTF IGF-1 IL-1
Neurotrophic factorsOxidative injury
Bax SP
JMT, AS
JTSL
CASY
JMT JMT JMTJMT, QT
TM, YQ
TB, MA
EA, MX
JTSL, AS
Yam, SA
CASY
XTQTXKL
QY
TM
EA
JTSL
AS: astragalus
CASY: compound of astragalus, salvia, and yam
EA: electroacupunctureJMT: jinmaitongJTSL: jiangtangshulufangMA: morus alba extractMX: moxibustionQT: qitengtongluoyin
QY: qingyingtangSA: salviaTB:tangbikangTM: tangmoningXKL: xiaokelingXT: xiaoketongbikeliYQ: yiqitongluozufang
Figure 2: Chinese medicine’s effects on Schwann cells and neurotrophic factors and its possible mechanisms of promoting nerve repair andregeneration in diabetic peripheral neuropathy.
3.3. IGF-1. IGF-1 promotes cell growth and proliferation,and it promotes the growth of axons. Recent studies haveshown that IGF-1 nourishes and supports motor andautonomic nerves. Decreased serum IGF-1 level and IGF-1 mRNA expression are shown in experimental diabeticrats, and administration of IGF-1 results in improvementof diabetic neuropathy [31]. Zeng et al. [19] applied reversetranscription polymerase chain reaction assay and confirmedthat the expression of IGF-1 mRNA was decreased in sciaticnerves in STZ-induced diabetic rats; the expression levelof IGF-1 mRNA and glucose was negatively correlated;treatment with Xiaokelingnongsuoye resulted in increasedexpression of IGF-1 mRNA in sciatic nerves. Xu et al. [20] setup a rat model of diabetic peripheral neuropathy and inves-tigated Qingyingtang’s effects on sciatic nerve conductionvelocity, histopathological changes, and the expression ofIGF-1 in tissue. They found that Qingyingtang enhanced sci-atic nerve conduction velocity, improved histopathologicalchanges, and increased the expression of IGF-1 in serum andtissue, confirming that Qingyingtang nourishes the sciaticnerve and promotes the sciatic nerve repair, possibly viaincreasing expression of IGF-1. Another study reported thatTangmoning can improve pathological changes in the sciaticnerve in rats, and it has protective effects on DPN, whichmight be related to its upregulation of the expression ofIGF-1 protein [21]. Yin et al. [16] proved that moxibustion
can upregulate IGF-1 mRNA expression of sciatic nerve indiabetic rats.
3.4. Interleukin. Interleukin 1 (IL-1) plays a central rolein the regulation of immune and inflammatory responses.It promotes cell proliferation and generation of othercytokines, and regulates metabolism. Recent studies foundthat IL-1 and IL-6 have functions of promoting regenerationof peripheral nerves; Schwann cell can secret IL-1 whichpromotes Schwann cells’ secretion of NGF; IL-6 can promotenerve regeneration of via up-regulating the expression ofCNTF mRNA [32–34]. It has not been reported that Chinesemedicine promotes nerve repair and regeneration via inter-leukin. Only a few studies reported that Chinese medicineinhibited inflammation factors in diabetes, so that improvedthe nerve impairment in DPN. Zhang et al. [22] administereddifferent dosages of Xiaoketongbi to STZ-induced diabeticrats for 2 months and found that Xiaoketongbi improvedthe peripheral neuropathy and decreased the levels of IL-1β, TNF-α, and CD54 in diabetic peripheral neuropathy rats,suggesting Xiaoketongbi relieves and improves diabetic neu-ropathy by means of inhibition of inflammation in diabetes.
4. Conclusion
Diabetic peripheral neuropathy is the result of multiplefactors, and the repair and regeneration of peripheral
12 Evidence-Based Complementary and Alternative Medicine
nerves are very complicated procedures that are regulatedby multiple factors; furthermore, the micro-environmentthat is needed for nerve repair and regeneration is notof single factor but composed of multiple related fac-tors. Recent studies have shown that Chinese medicineinhibits apoptosis, promotes proliferation in Schwann cells,and increases expression of multiple neurotrophic factors;therefore, Chinese medicine can improve nerve repair andregeneration in DPN (Figure 2). Chinese medicine has theadvantage of providing multiple therapeutic effects on mul-tiple targets, compared with Western medicine, which usesconventional chemical agents and focuses on a single target.Therefore, to a certain extent, the effective single herb orcompound of Chinese medicine might offer a more suitablemicro-environment, one that is neurologically and physical-ly needed for promoting repair and regeneration of nerves.
As we discussed in this paper, some studies investi-gated a single factor, thus, limited in explanations of themechanisms of Chinese medicine’s effects on nerve repairand regeneration. Although some Chinese medicine showedeffectiveness in vitro studies, it might not be effectiveclinically, because in vitro cultured cells independentlysurvive in an artificial environment, which is very differentfrom the environment in vivo. Because of the diversity ofpatterns of Chinese medicine, uncertainty about activitiesof various ingredients, difficulty of quality control, andunknown interactions between components in the sameChinese medicine compound, research on the mechanismsis very difficult to get further. In short, further research isneeded to clarify Chinese medicine’s clinical value and themechanisms of Chinese medicine’s functions of nerve repairand regeneration in DPN. Future studies should be carriedout with emphasis on both prevention and treatments toclarify the mechanisms by which Chinese medicine promotesnerve repair and regeneration; in the meantime, we need toexplore and block the factors that inhibit nerve repair andregeneration.
Acknowledgment
This work was supported by Natural Science Foundation ofBeijing (no. 7122147).
References
[1] X. C. Liang, “Diabetic peripheral neuropathy,” in Guidelinesfor Diagnosis and Treatment of Diabetes with Integrative Med-icine 2010, L. Lin, Ed., pp. 19–27, Military Medical SciencePress, Beijing, China, 1st edition, 2010.
[2] L. Q. Sun, X. C. Liang, H. Zhang et al., “Effects of medicatedserum of Jinmaitong capsule on proliferation and expressionof nerve growth factor in Schwann cells cultured in high glu-cose,” Zhonghua Zhong Yi Yao Zazhi, vol. 24, no. 8, pp. 1019–1022, 2009 (Chinese).
[3] B. S. Wu, W. J. Wang, and W. H. Chen, “Effect of allyl glycosideextracted from Herba Rhodiolae on activity and proliferationof cultured Schwann cells under high glucose condition,”Zhongguo Zhong Xi Yi Jie He Zazhi, vol. 29, no. 2, pp. 153–155,2009 (Chinese).
[4] J. L. Ji, D. S. Chen et al., “Experiment study of nourishing yin,invigorating qi, extinguishing wind, promoting blood circu-lation and draining collateral method of the sciatic nerveSchwann cells apoptosis of diabetic rats,” Zhongguo Zhong YiJi Zheng, vol. 18, no. 8, pp. 1304–1306, 2009 (Chinese).
[5] X. Y. Liu, Y. Y. Zhang, J. Q. Zhang et al., “Effect of astragalus,salvia, yam and its compound on apoptosis of Schwann cellsco-cultured with endothelial cells in high glucose,” Zhong YaoYao Li Yu Lin Chuang, vol. 26, no. 1, pp. 41–44, 2010 (Chinese).
[6] L. Zhao, X. C. Liang, H. Zhang et al., “Effects of Chinese herbalmedicine Jinmaitong-medicated serum on inducible nitricoxide synthase and NADPH oxidase p22-phox subunit of ratSchwann cells cultured in high-glucose medium,” Journal ofChinese Integrative Medicine, vol. 9, no. 3, pp. 299–305, 2011(Chinese).
[7] Y. L. Piao, X. C. Liang, L. Zhao et al., “Effects of medicatedserum containing Jinmaitong on 8-OHdG and active caspase3 of Schwann cells in high glucose medium,” Yi Xue Yan JiuZazhi, vol. 40, no. 10, pp. 35–39, 2011 (Chinese).
[8] L. Qu, X. C. Liang, Q. L. Wu et al., “Effects of Jinmaitong cap-sule on nerve growth factor in diabetic rats,” Zhongguo ZhongYao Za Zhi, vol. 33, no. 21, pp. 2539–2544, 2008 (Chinese).
[9] J. S. Deng and H. Zhang, “Possible preventive and therapeuticmechanism of Qitengtongluoyin on experimental diabeticneuropathy rats,” Zhongguo Lin Chuang Yao Xue Zazhi, vol.16, no. 4, pp. 242–245, 2007 (Chinese).
[10] S. J. Yu, L. Zhang, M. Wang et al., “Effect of Tangmoninggranular preparation on expression of nerve growth factorgene of sciatic nerve in diabetic rats,” Zhonghua Nei Fen MiZazhi, vol. 20, no. 2, pp. 169–170, 2004 (Chinese).
[11] Y. Xu and J. Yang, “Protective mechanisms of kidney-nour-ishing and collateral-unblocking therapy for peripheral neu-ropathy in experimental diabetic rats,” Shanghai Zhong Yi YaoZazhi, vol. 43, no. 9, pp. 67–69, 2009 (Chinese).
[12] J. Wang and T. H. Liu, “Tangbikang’s effects on serum nerverelated factor and expression of never related factor gene indiabetic rats,” Zhongguo Shi Yan Fang Ji Xue Zazhi, vol. 16, no.6, pp. 160–163, 2010 (Chinese).
[13] S. T. Ma, X. K. Zhang et al., “Effect of morus alba extract onnerve growth factor and myelin basic protein in diabetic rats,”Zhongguo Zhong Yi Ji Chu Yi Xue Zazhi, vol. 13, no. 10, pp.760–763, 2007 (Chinese).
[14] H. S. Dong, Q. J. Zhang, Q. Yang et al., “Experimental studyof nerve growth factor of sciatic nerve of rats with diabetesperipheral neuropathy accommodated by electroacupunc-ture,” Zhongguo Kang Fu Li Lun Yu Shi Jian, vol. 12, no. 8, pp.730–732, 2007 (Chinese).
[15] Z. Y. Huang, X. Zou, K. F. Wang et al., “Effect of electroacu-puncture on mRNA expression of NGF and IGF-1 in sciaticnerve of diabetic rats,” Zhong Xi Yi Jie He Yan Jiu, vol. 2, no. 2,pp. 57–60, 2010 (Chinese).
[16] H. Y. Yin, J. Wang, L. B. Xu et al., “Mechanism of peripheralneuroprotection induced by moxibustion treatment in ratswith diabetic peripheral neuropathy,” Shanghai Zhen JiuZazhi, vol. 27, no. 1, pp. 41–44, 2008 (Chinese).
[17] P. Y. Wang, X. C. Liang, L. Q. Sun et al., “Effects of Jinmaitongcapsule on expression of ciliary neurotrophic factor in diabeticrats,” Zhongguo Zhong Xi Yi Ji Jiu Zazhi, vol. 17, no. 1, pp. 3–6,2010 (Chinese).
[18] P. Y. Wang, X. C. Liang, H. Zhang et al., “Effect of Jinmaitongcapsule medicated serum on ciliary neurotrophic factor of ratSchwann cells in high glucose medium,” Zhong Yi Zazhi, vol.51, no. 8, pp. 736–739, 2010 (Chinese).
Evidence-Based Complementary and Alternative Medicine 13
[19] J. Z. Zeng, K. L. Dong, G. C. Li, L. M. Li et al., “Effect of Xi-aokelingnongsuoye on mRNA expression of insulin-likegrowth factor-1 in sciatic nerve of streptozotocin-inducedDiabetic Rats,” Zhong Nan Da Xue Xue Bao (Yi Xue Ban), vol.30, no. 1, pp. 49–52, 2005 (Chinese).
[20] X. P. Xu, J. Yang, P Zhu et al., “Experimental study on nerveprotective effect of Qingyingtang on rats with diabetic periph-eral neuropathy,” Zhongguo Zhong Yi Ji Chu Yi Xue Zazhi, vol.15, no. 11, pp. 836–838, 2009 (Chinese).
[21] W. Wang, S. J. Yu, C. N. Yu et al., “Influences of Tangmoninggranules on sciatic expression of NGF and IGF-1 proteins inrats with diabetic peripheral neuropathy,” Beijing Zhong Yi YaoDa Xue Xue Bao, vol. 33, no. 5, pp. 346–349, 2010 (Chinese).
[22] X. K. Zhang, F. B. Meng, Y. H. Duan et al., “Effects of Xi-aoketongbi granula on IL-α,TNF-β,and CD (54) of diabeticperipheral neuropathy in rats,” Shanxi Yi Xue Zazhi, vol. 37,no. 9, pp. 1136–1137, 2008 (Chinese).
[23] M. W. Kalichman, H. C. Powell, and A. P. Mizisin, “Reactive,degenerative, and proliferative Schwann cell responses inexperimental galactose and human diabetic neuropathy,” ActaNeuropathologica, vol. 95, no. 1, pp. 47–56, 1998.
[24] K. Sango, T. Suzuki, H. Yanagisawa et al., “High glucose-induced activation of the polyol pathway and changes of geneexpression profiles in immortalized adult mouse Schwanncells IMS32,” Journal of Neurochemistry, vol. 98, no. 2, pp. 446–458, 2006.
[25] A. M. Vincent, M. Brownlee, and J. W. Russell, “Oxidativestress and programmed cell death in diabetic neuropathy,”Annals of the New York Academy of Sciences, vol. 959, pp. 368–383, 2002.
[26] C. L. Delaney, J. W. Russell, H. L. Cheng, and E. L. Feldman,“Insulin-like growth factor-I and over-expression of Bcl-xLprevent glucose-mediated apoptosis in Schwann cells,” Journalof Neuropathology and Experimental Neurology, vol. 60, no. 2,pp. 147–160, 2001.
[27] Y. T. Wang and X. M. Lu, “Neurotrophic factors and theirmechanisms in repair of peripheral nerve injury,” Ren Min JunYi, vol. 49, no. 6, pp. 359–361, 2006 (Chinese).
[28] G. Pittenger and A. Vinik, “Nerve growth factor and diabeticneuropathy,” Experimental Diabesity Research, vol. 4, no. 4, pp.271–285, 2003.
[29] J. Zhang, Z. R. Chen, Z. W. Chen, G. J. Zhang et al., “Experi-mental study on enhancement of rat sciatic nerve regenerationby ciliary neurotrophic factor,” Zhonghua Chuang ShangZazhi, vol. 26, no. 4, pp. 239–242, 1999 (Chinese).
[30] A. P. Mizisin, Y. Vu, M. Shuff, and N. A. Calcutt, “Ciliary neu-rotrophic factor improves nerve conduction and amelioratesregeneration deficits in diabetic rats,” Diabetes, vol. 53, no. 7,pp. 1807–1812, 2004.
[31] M. H. Chen, P. R. Chen, M. H. Chen, S. T. Hsieh, and F. H. Lin,“Gelatin-tricalcium phosphate membranes immobilized withNGF, BDNF, or IGF-1 for peripheral nerve repair: An in vitroand in vivo study,” Journal of Biomedical Materials Research—Part A, vol. 79, no. 4, pp. 846–857, 2006.
[32] T. Shuto, H. Horie, N. Hikawa et al., “IL-6 up-regulates CNTFmRNA expression and enhances neurite regeneration,” Neu-roReport, vol. 12, no. 5, pp. 1081–1085, 2001.
[33] D. Lindholm, R. Heumann, M. Meyer, and H. Thoenen,“Interleukin-1 regulates synthesis of nerve growth factor innon-neuronal cells of rat sciatic nerve,” Nature, vol. 330, no.6149, pp. 658–659, 1987.
[34] J. Yang, L. Yu, X. Z. Qiu et al., “Experimental study on the roleof IL-1β in Schwann cells inducing and activation,” ZhonghuaXian Wei Wai Ke Zazhi, vol. 28, no. 2, pp. 142–144, 2005(Chinese).
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