Study on the action and its mechanisms of estrogen effective

cell-targeting active components in Chinese medicine

Jianzhao Niu

Beijing University of Traditional Chinese Medicine

中药活性成分靶向雌激素效应细胞作用机制研究

Beijing University of Traditional Chinese Medicine

北京中医药大学是中国重点大学；

拥有充足的教学科研设施和附属医院。

Many kinds of Chinese medicine have been widely applied in women health protection and treatment of gynecological diseases. Their effects on the target points and the consequent molecular changes inside human body account mainly for their pharmacological functions.

中药广泛应用于妇科保健和疾病的治疗；中药疗效是药物作用于体内

靶细胞，并通过一定的分子机制实现的。 Estrogen receptor is essential target point for Chinese

medicine in estrogen effective cells. The expression level and ratio of different estrogen receptor subtypes are key factors that determine the function of Chinese medicine.

雌激素受体是中药作用于效应细胞的重要靶点，雌激素受体不同亚型

表达及其比例是影响药物作用的重要因素。

雌二醇及部分植物雌激素的分子结构

Molecular structure of β-estradiol and some kind of estrogen receptor modulators

HO

OH

HO

OH

HO

OOH

O

HO

HO

OOH

O

HO

大豆甙元

OH

OH

O

OOH

OH

O

OOH

OH

daidzein金雀黄素

17β-Estradiol(E2) genistein17β-雌二醇

HO

OHCH3

H

HH

S

OF F

FF

FHO

OHCH3

H

HH

S

OF F

FF

F

ICI182,780雌激素受体拮抗剂

HO

OH

CN

HO

OH

CN

DPN 雌激素受体激动剂

部分中药活性成分的分子结构

Molecular structure of some kind of active components in Chinese medicine

O

O

OO

O

OO

O

O

R

O

O

O

R

O

O

OO

OO

O

丹参酮I 丹参酮IIA

补骨脂素 异补骨脂素

OO OOOO O

HO

HO

H

CH2

O

OH

H

CH3

H3C

HOOH

CH3

CH3

OH

HHO

HO

H

CH2

O

OH

H

CH3

H3C

HOOH

CH3

CH3

OH

H

蜕皮甾酮

红花黄色素A

O

OH

CH2OHHO

HOOH

H

HO

HO

CH2OH

H

O

H

OH

O

O

O O

O

OH

CH2OHHO

HOOH

H

HO

HO

CH2OH

H

O

H

OH

OO

OO

OO O

psoralen isopsoralen

ecdysterone

Tanshinone I Tanshinone IIA Hydroxysafflower yellow A

雌激素或类雌激素发挥作用的基本途径（启动效应开关）

Pathway of estrogen or estrogenic substances play their roles on target genes

Protein Synthesis

mRNA

DNA

E2

TATA Target gene

ER dimer（α/β）

DBD DBD

ERE

E2-ER complex combine to the specific sequence in the promotor of estrogen target genes

A/B C D E F 595DBD LBD

ERα

ERβ

AF-1HSP90 结合位点

AF-2

二聚化 二聚化

NLS NLS NLS

A/B C D E F 53018% 97% 30% 59% 18%

1

1

A/B C D E F 595DBD LBD

ERα

ERβ

AF-1HSP90 结合位点

AF-2

二聚化 二聚化

NLSNLS NLSNLS NLSNLS

A/B C D E F 53018% 97% 30% 59% 18%

1

1

Four kinds of Chinese medicine promoting blood circulation to remove blood statis and tonifying the kidney 研究选取的四种妇科常用中药（活血化瘀和补益类）

红花

川牛膝

丹参

补骨脂

红花等四种中药对性未成熟小鼠子宫组织ER-α表达的影响

Immuno-histochemistry results in animal models

Effects of four kinds of chinese medicine on ERα expression of uterus in rats

正常 己烯雌酚 红花

丹参

补骨脂

川牛膝

control diethylstilbestrol flos carthami

radix cyathulaeradix salviaemiltiorrhizae fructus psoraleae

红花等四种中药对性未成熟小鼠子宫组织 ER-β表达的影响

Immuno-histochemistry results in animal models

Effects of four kinds of chinese medicine on ERβ expression of uterus in rats

补骨脂

正常

红花己烯雌酚

川牛膝 丹参

control diethylstilbestrol flos carthami

radix cyathulaeradix salviaemiltiorrhizae fructus psoraleae

0.00

0.20

0.40

0.60

0.80

treatment

A 24hr

48hr

72hr

72hr+ICI182,780

▲

▲ ▲ ▲ ▲

▲

▲ ▲ ▲

▲

▲

▲

▲ △ △

△

▲

▲

Effects of six active components in chinese medicine on proliferation rate of MCF7 cells by MTT assay in vitro

1.control 2.estrodial (10-8M) 雌二醇 3. ecdysterome(10-6 M)蜕皮甾酮 4.saffcomin A (10-6M)红花黄色素A 5.psoralen (10-6M) 补骨脂素 6. isopsoralen (10-6M) 异补骨脂素 7.tanshinone I(10-6M) 丹参酮I 8.tanshinone IIA(10-6M)丹参酮IIA

1 2 3 4 5 6 7 8

For control ▲: P<0.01, △: P<0.05.

六种中药活性成分对MCF7细胞增殖的影响及ICI182,780的干预作用

异补骨脂素对T47D细胞增殖的影响

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

正常对照

雌二醇

异补骨脂素

异补骨脂素

异补骨脂素

异补骨脂素

异补骨脂素

组别

A

24h

48h

72h

▲

▲

▲

▲ ▲

▲

△

△

△

isops

oralen

10-9 M

0.1%EtoH

E 210

-9 Miso

psora

len10

-8 M

isops

oralen

10-7 M

isops

oralen

10-6 M

isops

oralen

10-5 M

TreatmentOpt

ical

den

sity

at 5

70nm

For control, ▲: P<0.01, △: P<0.05.,

Fig8. effects of isopsoralenon proliferation rate of T47D cells by MTT assay in vitro

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

正常对照

雌二醇

异补骨脂素

异补骨脂素

异补骨脂素

异补骨脂素

异补骨脂素

组别

A

24h

48h

72h

▲

▲

▲

▲ ▲

▲

△

△

△

isops

oralen

10-9 M

0.1%EtoH

E 210

-9 Miso

psora

len10

-8 M

isops

oralen

10-7 M

isops

oralen

10-6 M

isops

oralen

10-5 M

isops

oralen

10-9 M

0.1%EtoH

E 210

-9 Miso

psora

len10

-8 M

isops

oralen

10-7 M

isops

oralen

10-6 M

isops

oralen

10-5 M

TreatmentOpt

ical

den

sity

at 5

70nm

For control, ▲: P<0.01, △: P<0.05.,

Fig8. effects of isopsoralenon proliferation rate of T47D cells by MTT assay in vitro

Effects of isopsoralen on proliferation rate of T47D cells

0

0,1

0,2

0,3

0,4

0,5

0,6

EtOH 0.2% Estradiol 1×10-8 mol·L-1

Isopsoralen1×10-6 mol·L-1

Isopsoralen1×10-7 mol·L-1

24 h

48 h

control estrodial 10-8 M

isopsoralen 10-6M

isopsoralen 10-7 M

Opt

ical

den

sity

at 5

70nm

异补骨脂素对MDA-MB231细胞增殖的影响

Effects of isopsoralen on proliferation rate of MDA-MB231 cells

The estrogen receptors in target cells and their related signal pathway are essential mechanism by which Chinese medicine and its active components realize their parmacological functions.

靶细胞雌激素受体及相关信号转导途径是中药及其活性成分发挥效应

的重要机制 Chinese medicine and their active components also show the

effects on regulating the expression level and ratio of specific ER subtypes

中药及其活性成分可通过影响雌激素受体不同亚型表达及其比例发挥

临床疗效

Laboratory of cell and biochemistry

Research Team

Leader: Jianzhao Niu Xiaoou Xue Piwen Zhao Jian Li Yu Li Yadong Li Shiying Tao Fujian Zhao

Thank you！