Yun Yeon-SookRadiological and Medical Sciences Research Center KI

RAMS, Seoul, Korea

Syndrome Dose(cGy) Pathology Response Death time

Bone Marrow 100infection,

hemorrhagesurvivalprobable

3 weeks to2 month

Gastrointestinal 500depletion of

intestinal epithelium

survivalpossible

3 days to2 weeks

Central Nervous system 2000 edema

survivalimpossible

within 2 days

Acute Radiation Syndromes in Man after Whole-Body Irradiation

10 15 20 25 5 00

20

40

60

80

100

Time (Days)

Nor

mal

ized

to p

re-ir

radi

atio

n va

lue

(%)

GranulocytesPlateletsErythrocytesLymphocytes

Peripheral blood counts of ratsfollowing 500cGy whole-body irradiation

(Casarett, 1968)

We screened radioprotective immunostimulators from 70 medicinal plants which have been used in chinese medicine.

Ginsan

Ginseng Polysaccharide :

Gins + -an

Polysaccharide composed with(1 6)-Glucopyranoside and(2 6)-Fructofuranoside

OCH2 CH2

OOH

H

H

OH

H

OHO

OCH2 CH2

OOH

H

H

OH

H

OH

OCH2 CH2

OOH

H

H

OH

H

OH

OO

H

H

HO

HOH OH

H

O

H

OH

H

HO

HOH OH

H

O

H

OH

H

HO

HOH OH

H

O

H

control rad 100 2000

25

50

75

dose of Ginsan (mg/kg)

No.

of

colo

nies

/1 x

105 B

M c

ells

Effect of Ginsan on the formation of GM-CFU 5 days after sublethal irradiation

Irradiated

Non-irradiated control PBS 100mg/kg

Ginsan 200mg/kg

Ginsan WBCs x 103/L

3.463 0.236

0.368 0.052

0.711 0.047*

0.847 0.066*

Neutrophils x 103/L 0.367 0.043 0.0511 0.010 0.292 0.062* 0.259 0.092+

Lymphocytes x 103/L 2.975 0.259 0.254 0.041 0.410 0.046+ 0.468 0.033+

RBCs x 106/L 8.565 0.121 7.554 0.136 7.602 0.053 7.416 0.086

Platelets x 103/L 585.0 39.0 173.6 11.2 332.1 26.0* 433.0 14.8*

Results represent the mean SE of 10 mice per group(irradiated) and 6 mice per group(nonirradiated control). * P<0.001 increase versus PBS. + P<0.05 increase versus PBS.

Effect of Ginsan on the Peripheral blood hematology of mice 9 days after irradiation

0102030405060708090

100

0 2 4 6 8 10 12 14

Radiation dose(Gy)

Perc

ent S

urvi

val a

t 30

Day

s

LD50/30 =7.46PBS treated

LD50/30 =10.76Ginsan treated

Survival enhancing effect of Ginsan- Measurement of DRF (dose reducing factor)

Antisepticemic activity of Ginsan on the S. aureus peritoneal sepsis challenge

0102030405060708090

Cont. 0.01 0.025 0.05 0.25

Dose of Ginsan(mg/kg)

Perc

ent o

f sur

viva

l

0

10

20

30

40

50

60

70

Cont. 10 25 50 250 500

Dose of Ginsan(mg/kg)

Perc

ent o

f sur

viva

l

intraveneous injection oral intubation

*P<0.05

Mea

n Lu

ng S

core

Days Post-Virus Exposure

B

BB

B

J

J

J

J

H

H

HH

F F F

F

?

N

N

N

0 3 6 90

1

2

3

4

*

*

*

*

*

B Ginsan (200mg/kg)x4

J Ginsan (100mg/kg) x4

H Ginsan (50mg/kg) x4

F Ribavirin (75mg/kg) x10

N Saline

Effect of Ginsan treatment on lung consolidation scores in influenza A(H3N2) virus-infected mice

GinsanCt

-actin

IL-2

GM-CSF

IFN-

TNF-

IL-12

3 6 24h

IL-4

IL-10

IL-1

IL-5

3 6 24h

Generation of activated killer cells and increase of cytokine production by Ginsan

0

10

20

30

40

50

60

10 :1 30 :1 100 :1

E/T ratio

% c

ytot

oxic

ity

SC

OK432Ginsan

lentinan

Inhibitory effect of Ginsan on the experimental metastasis of B16-F10 melanoma

Agents

PBS

Ginsan

Inhibition of B16-F10 melanoma

counts % inhibition

533

278

-

44.2

PBS-control

Ginsan

• Generation and/or differentiation of SC • Cytokine production

Action Mechanism of Ginsan

B cellCell

expansion

Blastogenesis

IL-6GM-CSF

AK cell

Tumor

IL-1IL-12IL-15

IL-2IFN

Antitumor effect

IFNIFN

NK cellT cell

Ginsan

Macrophage

IL-3IL-6

TNFNO/O2

-

Mono/Gra Lym

Plt

BM

RBC

MRSA, VRSA

Bactericidal effect

Hematopoisis

• Mitogenic activity• Killer cell generation • Cytokine production

(Due to macrophage-derived toxic material production)

Ginsan