《研究生英文文献汇报》

研究生英文文献汇报Keywordsscutellarin;scutellarein;UGT;enzyme

inhibition.ContentsIntroductionExperimental

sectionResults

and

discussionConclusion1.

Introduction

In

therecent

years,another

important

drugmetabolizing

enzyme

UDP-glucuronosyltransferase(UGT)

has

been

demonstrated

to

exhibit

significantcontribution

towards

the

metabolism

of

clinical

drand

herbal

components,and

more

and

more

attentionhas

been

given

to

this

enzymes

(Malik

and

Black,2012;

Li

etal.,

2012).

UGTs

have

been

demonstrated

to

be

involved

in

themetabolic

elimination

of

many

important

endogenousubstances,

such

as

bilirubin,

bile

acid

and

estra(Erichsen

et

al.,

2010).

Guo

et

al.

showed

deglycosylation

process

of

liquirstrongly

enhanced

the

inhibitory

capability

towardUGTs

(2012).

Huang

et

al.

showed

strong

inhibition

of

glycyrrhetacid

towards

UGT1A3

and

2B7

(2012).

Liu

et

al.

also

used

in

vitro

incubation

system

to

fthe

strong

inhibition

of

deoxyschizandrin

andschisantherin

A

towards

UGT1A3

(2012).•Chemicals

and

reagents.Scutellarin,Scutellarein,4-MU,Tris-HCl,7-hydroxycoumarin,UDPGA(缓冲盐)，重组UGTs亚型（UGT1A1，UGT1A6，UGT1A9，UGT2B7），HPLC

reagents.2.

Experimental

section•Incubation

and

analysis

methods

for

inhibitioevaluation.After

5min

pre-incubation

at

37℃,

the

UDPGA

was

added

in

themixture

to

initiate

the

reaction.

The

incubation

time

was

120mUGT1A1

and

UGT2B7,

30min,or

UGT1A6

and

UGT1A9,

respectively.The

reactions

were

terminated

by

adding

100

mL

acetonitrile

wihydroxycoumarin

(100mM)

as

internal

standard.The

mixture

wascentrifuged

at

20000×g

for

10min,

HPLC

analysis.•Data

fitting

for

determination

of

inhibitionand

parameters

(Ki).The

reaction

velocity

was

determined

using

various

concentraof

4-MU

and

scutellarein.

The

data

were

fitted

using

Dixon

ploLineweaver–Burk

double

reciprocal

plot.

The

second

plot

witslopes

from

the

Lineweaver–Burk

plot

versus

the

concentratiscutellarein

was

utilized

to

calculate

the

Kivalue.Predictivivo

drug–drug

interaction

magnitude.•Prediction

of

in

vivo

drug–drug

interactionmagnitude.The

most

common

equation

for

drug–drug

interaction

predictiwas

employed

to

predict

the

AUC

alteration

of

coadministereddrugs

caused

by

co-administration

of

scutellarein.3.

Results

and

discussion

图2表明，100mM野黄芩苷对UGT1A1，UGT1A6，UGT1A9，UGT2B7的活性抑制率分别为48.8%、20.2%、36.1%、73.8%。同浓度野黄芩素对以上4种UGTs的活性抑制率分别为99.2%、89.8%、85.4%、86.4%。Figure

3.Figure

4.Figure

5.Figure

6.

野黄芩素对被测试UGTs的抑制作用表现出一定浓度的行为依赖性(A)。

Dxion图(B)和Lineweaver-Burk图(C)反映了抑制动力学类型；野黄芩素对被测试UGTs都有

竞争性抑制作用。

由Lineweaver-Burk图及其斜率计算得野黄芩素对被测试UGTs的Ki值分别为0.02、5.0、5.8、35.9(C).

本实验研究了野黄芩苷和野黄芩素对4种UGT的抑制作用。结果表明，野黄芩素比野黄芩苷对被测试UGTs表现出更强的抑制作用，提示野黄芩苷的去糖基化过程可增强其抑制作用，与文献报道相符(Guo

etal,2012)。

无论野黄芩素对被测试UGTs的体外抑制是否转化为体内抑制；在体内，