chinesemedicineindiabeticperipheralneuropathy...

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

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Evidence-Based Complementary and Alternative Medicine 3

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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


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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”


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

.


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).


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.


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


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).

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