姜 欣 濉 博士

인삼효능과 장내미생물인삼효능과 장내미생물

1st July 2011

高 丽 人 参高 丽 人 参Panax ginseng C.A. Panax ginseng C.A.

MeyerMeyer

Rhizome 뇌두 腦頭

Fruit 열매 果實

山蔘 (Wild Ginseng)

(Panax ginseng C.A. Meyer)

Peduncle 꽃대 花柄 Branch 가지 枝

Leaf 잎 は

Stalk 대 莖

Browse 새싹 筍

Root 삼근 蔘根

Ginseng root ring 가락지 蔘根指輪

Tertiary root 잔뿌리 細根

紅蔘 (Red Ginseng)

高丽人参高丽人参 (Korean Ginseng)

(Panax ginseng C.A. Meyer)

黑蔘 (Black Ginseng)

Steaming

Repetitive

Steaming

Shape of ginseng

Classification Contents(%) Note.

Saponin

Organic

Ginsenoside - Pharmacological

materials

3 ~ 6

Protopanaxadiol ginsenoside

Protopanaxatriol ginsenoside

Oleanolic acid ginsenoside

over 30 compounds

identified

Non-

Saponin

Carbohydrate 60~70Polysaccharides

(mono-, di-, tri-, and poly-), Fiber, pectin

Nitrogen-containing compound

12~16Protein, Peptides, Amino acid, Nucleic acid, Alkaloids

Fat-soluble compound

2

Lipids, Fatty acid, Essential oils, Phytosterols, Organic acids, Phenolics, Polyacetylenes, Terpenes

Water-soluble compound

0.05 Water-soluble Vitamines

Non-

Organic

Ash content

Water

4

9~11Minerals, Water

Composition of dried Ginseng

- Panax ginseng C. A. Meyer, indigenous to Korea, has long been a local specialty - Ginseng makes the pharmacological materials via the secondary metabolism

Ginsenosides- A class of steroid-like compounds, triterpene saponins, found exclusively in the plant genus Panax- Can be separated by column chromotography- Ginsenoside content can vary widely depending on species, location of growth, growing time before harvest, and methods of processing after harvest

The Classification of Ginsenoside

Protopanaxadiol (PPD) Protopanaxatriol (PPT) Oleanolic acid

PPD Type

Ra1, Ra2, Ra3, Rb1,Rb2, Rb3, Rc, Rd

Rg3, Rh2, Compound-K and so on

PPT Type

Re, Rg1, Rg2, Rf, Rh1,

F1, F3, R1, R2 and so on.

Oleanane Type

Ro

Rb1, Rb2, Rc, Rd, Re, Rg1 ~ 90% / total ginsenosides

R1O

1

2

3

45

67

8

9

10

11

1213

14 15

16

17

HOR3O

1819

20

2122

2324

2526

27

29 28

30

HO

1

2

3

45

67

8

9

10

11

1213

14 15

16

17

HOR3O

1819

20

R2

2122

2324

2526

27

29 28

30

COOR21

2

3

45

67

8

9

10

11

1213

14

15

16

17

R1O

18

19 21

30 29

22

2324

25 26

27

20

28

Class of Ginseng Saponin (Ginsenoside)

Korea Ginseng(Panax ginseng

C.A.Meyer)

Chinese Ginseng(Panax notaginseng

F.S.Chen)

American Ginseng (Panax

quinquefolium L.)

Total number of Ginsenosides

38 29 19

PPD type 21 14 13

PPT type 15 15 5

Oleanolic type 2 - 1

PD/PT ratio 1.33 0.99 2.15

Rg1/Rb1 ratio 0.81 1.01 0.10

Reviews in Ginseng Research. I, 277 (2007)

The Superiority of Korean Ginseng

Skin Care

Stress Improvement Brain

Vitalizing

ImmunityCirculation

No. 1 Health Functional Herb

Korean Ginseng

Rg1:Rb1 의 비율에 따른혈관신생능력의 차이

Circulation 110:1219-1225 (2004)

阴 (Yin)

PD 계열

Ginsenoside Rb1

阳 (Yang)

PT 계열

Ginsenoside Rg1

Yin and Yang of SaponinYin and Yang of Saponin

阴 (Yin)

- 진정 작용 - 스트레스 조절 - 항상성 유지 작용

阳 (Yang) - 혈액 순환 촉진 - 생체 활력 증진 - 병후 회복 촉진

음양이 조화로운

고려인삼

최고의 생약

Efficacy of SaponinEfficacy of Saponin

1) 62.5% : Good Bioavailability

2) 37.5% : Bad Bioavailability

Side Effect

20.3%(Diol only)

12.5%(Triol only)

4.5% (None)

62.5%(Diol + Triol)

pyrexia, 發熱 hot flush, 顔面紅潮Increase of heart beat, 心拍增加diarrhea, 泄瀉

Annual meeting & international symposium, The Korean society of food science and nutrition. (2004)

The Individual Variation of The Individual Variation of BioavailabilityBioavailability

0

2

4

6

8

10

12

14

16

Con

vers

ion

ratio

of G

inse

nosi

des

(um

ol/h

/g)

According to physical constitution,

the efficacy of Ginseng is various to individual.

J. Ethnopharmacol.122, 143 (2008)

Why??

Absorption, distribution Absorption, distribution and metabolism of and metabolism of

GinsengGinseng

(Drug. Metab. Dispos. 31, 1065)

Pla

sma

C 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Time in hours

Urin

e

Rg1, Rd,Re, Rb2,

RcRh1 Rb1 C-K

F1, Rh1C-K

0~3 h 4~6 h 6~12 h 12~24 h

Rh1

Rb1

C-K

F1 or Rh1

HydratedRh1

HydratedC-K

Ginsenosides and their degradation products

H

OHGlc-O

Glc-O

Ginsenoside Rb1 Ginsenoside RdH

OHGlc-O

Glc(1-2)Glc-O

H

OH

Glc(1-2)Glc-O

Araf(1-6)Glc-O

Ginsenoside RcH

OH

Glc-O

Araf(1-6)Glc-O

Ginsenoside MbH

OHAraf(1-6)Glc-O

HO

Ginsenoside Mc

HO

H

OH

HO

20(S)-Protopanaxadiol (PPD)

Glc-O

H

OH

Glc(1-2)

Glc(1-6)

Glc-O

Compound K

Ginsenoside Rb2H

OH

Glc(1-2)Glc-O

Arap(1-6)Glc-O

Compound OH

OH

Arap(1-6)Glc-O

Glc-O

H

OH

Arap(1-6)Glc-O

HO

Compound Y

H

OHGlc-O

HO

Ginsenoside F2

Transformation of Protopanaxadiol Ginsenosides

O-Glc(2-1)Rha

OHGlc-O

HO

Ginsenoside Re

O-Glc

OHGlc-O

HO

Ginsenoside Rg1

OH

OHGlc-O

HO

Ginsenoside F1

O-Glc(2-1)Glc

OHGlc-O

HO

Ginsenoside Rf

HO

O-Glc

OH

HO

Ginsenoside Rh1

HO

OH

OH

HO

Protopanaxatriol (PPT)

Transformation of Protopanaxatriol Ginsenosides

According to Physical constitution, the efficacy of Ginseng is various to individual

Requirement of Processed Ginseng for those who cannot transform the ginsenosides

About 20% of tested persons cannot transform the Ginsenosides

A. Ginsenoside Rb1 → CK B. Water Extract → CK

Max Min Mean±SD

Men 2032.00 41.37 565.24±544.92

Women 2889.87 31.03 786.51±648.95

Total 2889.87 31.03 646.14±591.39

Transformation Activity from Ginsenoside Rb1 to compound K (mol/h/g)

담즙분비

흡수

Ginseng

Ginsenosdies metabolized

by gut microorgani

msms

Absorption

LiverLiverMetabolite

Kidney

Distribution

Biol. Pharm. Bull.27, 1580 (2004)

Gut Microorganism and Bioavailability

뇨

담즙분비

흡수

Ginseng

Ginsenosdies metabolized

by gut microorgani

msms

Feces

Absorption

LiverLiverMetabolite

KidneyUrine

Distribution

The microbes in human intestine differ according to each person – total number and kinds. In same person, they can be changed according to aging and food.

Bacteroidaceae, Eubacterium

Bifidobacterium, Peptostreptococcus

Lactobacillus, E. coli

Streptococcus

Veillonella, Clostridium perfringens

Pseudomonas, Staphylococcus aureus

Biol. Pharm. Bull. 23, 1481 (2000)

Main intestinal bacteria resided in human colon

Recovery of ginsenoside Rb1 and compound K of the intestinal tracts and cumulative feces of germ-free and gnotobiotic rats 7 and 15h after oral administration of ginsenoside Rb1

nd, not detected

J. Pharm. Pharmacol. 50, 1155 (1988)

Intestinal Microorganism andIntestinal Microorganism and CompoundCompound KK

Change of Compound K and Rb1 concentrations in blood after oral administration of Ginsenoside Rb1, original Korean ginseng saponin,in the rats.

Ginsenoside Rb1 (200 mg/kg) was administered orally to rats, Compound K was detected in the plasma 1,2,4, 7, 15 or 24 h after administration.

Biol. Pharm. Bull. 21, 245 (1998)

Ginsenoside into BloodGinsenoside into Blood

Body Absorption and Urinary excretion

after oral administration of Original Ginsenoside.

Ginsenoside Rb1 (50mg) was orally administered into 3 male SD rats and the urine sample was collected periodically at 3h, 6h, 12 and 24h post-dosing.

Compound K (converted and absorbed saponin)

Ginsenoside Rb1 (original ginseng saponin)

Biol. Pharm. Bull. 28, 652 (2005)

Absorbed GinsenosideAbsorbed Ginsenoside

A) Plasma concentration time curve of CK following oral administration of ginseng extracts.

Mean ± S.D.

Cmax(ng/ml)

Tmax(h)

AUC (ng.h/ml)

27.89 ± 24.46

10.76 ± 2.07

221.98±221.42

Distribution of Compound K in Plasma

Compound K is only absorbed into human body through intestines by microorganisms’ work.

It is necessary to be transformed to gain the bioactive Compound K

J. Ethnopharmacol.122, 143 (2008)

Transforming Activities in Transforming Activities in the Human Bodythe Human Body

AA

J. Pharmacol. Sci. 95, 153 (2004)

Ginsenosides and metabolites through Ginsenosides and metabolites through gutgut

Activity of Activity of Ginsenoside Ginsenoside MetaboliteMetabolite

a not detectable

ED50, 50% growth-inhibitory concentration against tumor cells

Reviews in Ginseng Research. I, 82 (2007)

Cytotoxicity of Gensenosides Cytotoxicity of Gensenosides against tumor cellsagainst tumor cells

Inhibition of tumor cell proliferation by CK is nearly equal to that

of cyclophophamide, one of the most effective antitumor agent.

J. Asian Natural Products Research. 8, 519 (2006)

IC50, 50% growth-inhibitory concentration against tumor cellsB16-BL6 – Mouse high-metastatic melanoma, HepG2 – Human HepatomaK562 – Human myeloid leukemia, 95-D – Human high-metastatic lung carcinoma

Cytotoxicity of Ginsenosieds Cytotoxicity of Ginsenosieds against tumor cellsagainst tumor cells

0 10 20 30 40 50 60 70

0

10

20

30

40

50

60

LLC

Day 0 Day 21 Rb1, 25 mg/kg, p.o.

Inhi

bitio

n of

met

asta

sis

(%)

Rb1-hydrolyzing potential (%)

Lung metastasisRb1-hydrolyzing potential

Association of Rb1-hydrolyzing Association of Rb1-hydrolyzing Potentials with Antimetastatic Potentials with Antimetastatic

activity of Rb1activity of Rb1

The Ginsenoside Rb1 and its metabolite Compound K markedly inhibited lung

metastasis of B16-BL6 melanoma cells through oral administration. In contrast,

Compound K only resulted in a significant inhibition of lung metastasis through i.v.

0 100 200 300 400 500

CK (0.5mg)

Rb1 (0.5mg)

Ginseng(1mg)

Control

0 100 200 300 400

CK (0.5mg)

Rb1 (0.5mg)

Control

No. of colonies ± S.D.

**

**

* *

J. Ginseng Res. 31, 1 (2007)

Inhibitory effect on lung Inhibitory effect on lung metastasismetastasis

CK

Ginsenoside Metabolite is Ginsenoside Metabolite is the Active Principlethe Active Principle

Ginsenoside Ginsenoside Compound K ResearchCompound K Research

Primary Tumor Lung metastasis

Inh

ibit

ion

(%

)

ControlCK CDDP(mg/kg)

*

0

20

40

60

80

100

120

140

5 10 7

1

1

2

CDDPCK (mg/kg)Control

**

*

0

50

00

50

00

5 10 7CK CDDP(mg/kg)

Lung metastasis

Injection of LLC

Day 1: CDDP, i.v.

Day 1-14: CK, p.o.

Effects of Compound K Effects of Compound K on Growth of Primary Tumor and Metastasis to

Lymph Nodes

Effets of compound K on the ear thickness of mice (each 8 heads)

induced by oxazolone (. #P<0.05, ##P<0.01, *P<0.05, **P<0.001

Normal (Steroid antiphlogistics)

O + 0.05% betamethasone

O + 0.05% CK

O + 0.02% CK

O + 0.05% Rb1

O + 0.02% Rb1

Oxazolone only (Chemical Allergen for immuno-stimulation)

Immunopharmacology. 5, 1183 (2005)

Inhibitory effect on the ear thickness Inhibitory effect on the ear thickness of miceof mice

Protective effect of orally administered ginsenoside Rb1 and

compound K on t-BHP-induced hepatotocixity in mice

Liver Int. 25, 1069 (2005)

Protective effect on hepatotoxicity in Protective effect on hepatotoxicity in micemice

Acetic acid-induced abdominal writhing test of groups of mice

which received Saline, Diclofenac (5mg/Kg), Red Ginseng

(250mg/Kg), Compound K (5mg/Kg).

Anti-pain experiment of Ginseng

0

20

40

60

80

Control Diclofenac Red Ginseng CK

Group

Th

e N

um

ber

of

Wri

thin

g

Metabolab Inc. (2009)

Anti-pain effect of Ginseng in miceAnti-pain effect of Ginseng in mice

Inhibitory effect of ginseng and some ginsenosides on mouse

passive cutaneous anphylaxis reaction induced by lgE-antigen

complex. These agents at a dose of 25mg/Kg were orally treated

Noraml Ginseng Rb1 Compound K

Reviews in Ginseng Research. I, 83 (2007)

Inhibitory effect on mouse passive Inhibitory effect on mouse passive cutaneous anphylaxiscutaneous anphylaxis

Con

CK (5uM) CK (10uM)

Rb1 (10uM) Rb1 (20uM)

Compound K decreases the adipocyte differentiation (3T3-L1 Cell line) more than Ginsenoside Rb1

two times concentrationMetabolab Inc. (2009)

Inhibitory effect of Compound K Inhibitory effect of Compound K in Fat cell differentiationin Fat cell differentiation

1. A, B; in vitro assay and C,D; in vivo study in diabetes model mouse

2. Effect of anti-diabetes in diabetes model mouse by Compound K

Biol. Pharm. Bull. 30, 2196 (2007)

Effects of Compound K-Effects of Compound K-Anti-diabetesAnti-diabetes

Ikuo, S., J. Ginseng Res. 31, 1, (2007)

복수

간 종양

나선 종양

2002.8 MRI 2003.3 MRI

75 세 남성 ( 간암）

7 개월 후

농도 (ug/mL)

CK

흑색종

섬유육종

Compound K

Compound K

실험

군 대

비 %

실험

군 대

비 %

Effects of Compound K-Effects of Compound K-Anti-tumorAnti-tumor

H

OHGlc-O

HO화합물 K

(Ginsenoside M1)

항염증 효과항염증 효과Park EK, Shin YW, Lee HU, Kim SS, Lee YC, Lee BY, Kim DH. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharm Bull. 2005 28:652-6.

간 보호 효과간 보호 효과

피부 보호 효과피부 보호 효과Shin YW, Bae EA, Kim SS, Lee YC, Kim DH. Effect of ginsenoside Rb1 and compound K in chronic oxazolone-induced mouse dermatitis. Int Immunopharmacol. 2005 5:1183-91.

당뇨 개선 효과당뇨 개선 효과

Park EJ, Zhao YZ, Kim J, Sohn DH. A ginsenoside metabolite, 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, triggers apoptosis in activated rat hepatic stellate cells via caspase-3 activation. Planta Med. 2006 72: 1250-3.

Chang TC, Huang SF, Yang TC, Chan FN, Lin HC, Chang WL. Effect of ginsenosides on glucose uptake in human Caco-2 cells is mediated through altered Na+/glucose cotransporter 1 expression. J Agric Food Chem. 2007 55:1993-8.

항암 효과항암 효과Cho SH, Chung KS, Choi JH, Kim DH, Lee KT. Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells. BMC Cancer. 2009 Dec 18;9:449.

신경 퇴화 보호 효과신경 퇴화 보호 효과

Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K. Ab(25-35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, A metabolite of protopanaxadiol-type saponins. Neuropsychopharmacology. 2004 29:860-8.

항알레르기 효과항알레르기 효과

Choi K, Kim M, Ryu J, Choi C. Ginsenosides compound K and Rh2 inhibit tumor necrosis factor-alpha-induced activation of the NF-κB and JNK pathways in human astroglial cells. Neurosci Lett. 2007 421:37-41.

Bae EA, Choo MK, Park EK, Park SY, Shin HY, Kim DH. Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity. Biol Pharm Bull. 2002 25:743-7.

Kim DY, Park MW, Yuan HD, Lee HJ, Kim SH and Chung SH. Compound K Induces Apoptosis via CAMK-IV/AMPK Pathways in HT-29 Colon Cancer Cells. J. Agric. Food Chem., 2009, 57 (22), pp 10573–10578.

Effects of Compound KEffects of Compound K

Fermented Ginseng ResearchFermented Ginseng Research

1. Fermentation with the MicroorganismsMicroorganisms..

2. Incubation with Special EnzymesSpecial Enzymes

: : a few glycosidases can cleave the glycosidic bond in ginsenosides.

3. Modification of pHpH controlling HeatHeat and PressurePressure.

Some glycosidic bond in ginsenosides are more weaker than others.

4. CombinationCombination of above methods.

Ginsenosides

Active Ginsenoside Metabolites

Transformation Methods of Transformation Methods of GinsenosidesGinsenosides

Identification of GinsenosidesIdentification of Ginsenosides

Chromatogram of HPLC

Our HPLC System 1 with Evaporative Light Scattering Detector

Rb1, Rg2, Rh1

Rg1, Re

Rd

Rb2, Rb3

Rc, F1

Rg3

Compound K

PPD

Rk1, Rg5

Compound Y

Rf

Our HPLC System 2 with UV/VIS Absorbance Detector

Ginsenoside Transformation and DegradationGinsenoside Transformation and Degradation

DegradedGinsenosides

Active GinsenosidesRg3, Rh2, Com-K, etc.

Active Ginsenosides

• Intact Ginseng

Ginsenoside Transformation and DegradationGinsenoside Transformation and Degradation

- Metabolab’s Fermented Ginseng

- Hard Physical Treatment

Fermentation

Heat & Pressure

TLC HPLC

Screening the Useful Microorganisms

Lactobacillus alimentarius Identities = 1496/1507 (99%); E value = 0

> M-1 (1559 letters)AGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCATGCCTAATACATGCAAGTCGAACGAACTTTCCTTTTGATTGATGCTTGCATCATGATTTAGATCTAAGTGAGTGGCGGACGGGTGAGTAACACGTGGGTAACCTGCCCAGAAGTGGGGGATAACATTTGGAAACAAGTGCTAATACCGCATAACAACATTAAACACATGTTTTTTGTTTAAAAGATGGTTTTGCTATCTCTTCTGGATGGACCCGCGGCGTATTAGCTAGTTGGTGAGGTAATAGCTCACCAAGGCGATGATACGTAGCCGACCTGAGAGGGTAATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGGAATCTTCCACAATGGACGAAAGTCTGATGGAGCAATGCCGCGTGAGTGAAGAAGGTTTTCGGATCGTAAAACTCTGTTGTTGAAGAAGAACATATGTGAGAGTAACTGTTCACGTACTGACGGTATTCAACCAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTATTGGGCGTAAAGAGAATGTAGGCGGTTCATTAAGTTTGAAGTGAAAGCCCTCGGCTCAACCGAGGAAGTGCTTCGAAAACTGGTGAACTTGAGTGCAGAAGAGGAAAGTGGAACTCCATGTGTAGCGGTGGAATGCGTAGATATATGGAAGAACACCAGTGGCGAAGGCGGCTTTCTGGTCTGTAACTGACGCTGAGATTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGAGTGCTAAGTGTTGGAGGGTTTCCGCCCTTCAGTGCTGCAGCTAACGCATTAAGCACTCCGCCTGGGGAGTACGATCGCAAGATTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATACCATGAAAAGCTAAGAGATTAGTCTTTCCCTTCGGGGACATGGATACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATTATCAGTTGCCAGCATTCAGTTGGGCACTCTGGTGAGACTGCCGGTGATAAACCGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGTCGGTACAACGTGTTGCGAACTCGCGAGGGCAAGCAAATCACTTAAAACCGATCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGCTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTTTGTAACACCCAAAGTCGGTGGGGTAACCCTTCGGGGAACTAGCCGCCTAAGGTGGGACAAATGATTAGGGTGAAGTCGTAACAAGGTAGCCGTAGGAGAACCTGCGGCTGGATCACCTCCTT

Identification: KCTC Deposited Microorganisms> M-2 (1543 letters)AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAATACATGCAAGTCGAACGCACAGCGAAAGGTGCTTGCGCCTTTCAAGTGAGTGGCGAACGGGTGAGTAACACGTGGACAACCTGCCTCAAGGCTGGGGATAACATTTGGAAACAGATGCTAATACCGAATAAAACTTAGTGTCGCATGACAAAAAGTTAAAAGGCGCTTCGGCGTCACCTAGAGATGGATCCGCGGTGCATTAGTTAGTTGGTGGGGTAAAGGCCTACCAAGACAATGATGCATAGCCGAGTTGAGAGACTGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCTGCAGTAGGGAATCTTCCACAATGGGCGAAAGCCTGATGGAGCAACGCCGCGTGTGTGATGAAGGCTTTCGGGTCGTAAAGCACTGTTGTATGGGAAGAACAGCTAGAATAGGAAATGATTTTAGTTTGACGGTACCATACCAGAAAGGGACGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGTCCCGAGCGTTATCCGGATTTATTGGGCGTAAAGCGAGCGCAGACGGTTTATTAAGTCTGATGTGAAAGCCCGGAGCTCAACTCCGGAATGGCATTGGAAACTGGTTAACTTGAGTGCAGTAGAGGTAAGTGGAACTCCATGTGTAGCGGTGGAATGCGTAGATATATGGAAGAACACCAGTGGCGAAGGCGGCTTACTGGACTGCAACTGACGTTGAGGCTCGAAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACGATGAACACTAGGTGTTAGGAGGTTTCCGCCTCTTAGTGCCGAAGCTAACGCATTAAGTGTTCCGCCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCTTTGAAGCTTTTAGAGATAGAAGTGTTCTCTTCGGAGACAAAGTGACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCCAGCATTCAGATGGGCACTCTAGCGAGACTGCCGGTGACAAACCGGAGGAAGGCGGGGACGACGTCAGATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGCGTATACAACGAGTTGCCAACCCGCGAGGGTGAGCTAATCTCTTAAAGTACGTCTCAGTTCGGATTGTAGTCTGCAACTCGACTACATGAAGTCGGAATCGCTAGTAATCGCGGATCAGCACGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTTTGTAATGCCCAAAGCCGGTGGCCTAACCTTTTAGGAAGGAGCCGTCTAAGGCAGGACAGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTAGGAGAACCTGCGGCTGGATCACCTCCTT

Leuconostoc mesenteroides Identities = 1541/1543 (99%); E value = 0

Paper Study & Broad

Screening

In-depth Screening

Identification & Process

Optimization

- Search for Articles, Patents and etc.

- Screen Candidates with crude ginsenoside

- TLC: qualitative screening

- Classic identification: morphologic character

- Molecular identification: rRNA sequencing

- For the purpose of patent procedure Original Deposit to KCTC

- Optimization

- Monitor biochemical conversion ability of microbes

- Test usable medium, culture condition and etc.

- HPLC: quantitative screening

Selection and Identification of Selection and Identification of MicroorganismsMicroorganisms

Screening of Ginsenosides Transformation

Compound KCompound K

OriginalOriginalGinseng SaponinsGinseng Saponins

Korean Ginseng高麗인삼

醱酵인삼

Timecourse of the Transformation of Ginsenosides by MicroorganismMicroorganism

% Ginsenoside

Rb1 6.92

Rg1 6.67

Rf 4.55

Rh1 9.88

Rg3 5.22

Rh2 0.61

CK 26.89

Other 39.26

Total 100.0

0% 26.89%

20% < Compound K (CK)

Compound K

Standard Profile of Fermented Standard Profile of Fermented GinsengGinseng

- 음양이 조화로운 고려인삼 : 최고의 생약

- 인삼의 생리활성 본체 : 인삼사포닌

- 생체대사 활성도의 차 : 효능의 차이와 부작용

- 생명공학기법을 통한 발효인삼 개발

- 발효인삼의 핵심물질은 Compound K

- Compound K 의 효능 : 항암 , 항관절염 , 항당뇨

병 ,

간 보호 , 항피부노화 , 항뇌신경퇴화 , 항염증 등

- 발효인삼의 항관절염 효능 평가 시험

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