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2016 ICB BALIKPAPAN
Arung ET. 2016. Forest biodiversity for medicine andcosmetic. International Conference on Biodiversity,
Balikpapan, 14-16 January 2016 [Organized by Societyfor Indonesian Biodiversity, University of Mulawarman
Samarinda & University of Sebelas Maret Surakarta]
1
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Forest Biodiversityfor Medicine and Cosmetic
Enos Tangke ArungEnos Tangke Arung
ICSIBMU-Balikpapan, 14-16th January 2016
Laboratory of Forest Products ChemistryForestry Faculty, Mulawarman University
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1. Introduction
2. Forest Potency in EastKalimantan
3. Results and Products
4. Remarks
Outline:
1. Introduction
2. Forest Potency in EastKalimantan
3. Results and Products
4. Remarks
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1. Introduction1. Introduction
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Indonesia is one of theworld’s top biodiversityrich countries(www.fauna-flora.org)
17,000 islands12% of the world’smammal16% of the world’sreptiles and amphibians,
17,000 islands12% of the world’smammal16% of the world’sreptiles and amphibians,
17% of the world’s birds25% of global fishpopulations (www.fauna-flora.org)
10% of the world’s Plants>400 of dipterocarps25,000 flowering plants(www.aseanbiodiversity.org)
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Recreation
Carbon stock
Economic source
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Loss of Forestbiodiversity :
Palm oil plantation
Coal mining
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Coal mining effect ?
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InternationalNGOLocal NGO
LocalGovernment
ForestPolice
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Scientist
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The use of Forestry Biodiversity ?????
Added value of Non TimberForest Product
Added value of Non TimberForest Product
Increase economic value andwalfare of People near forest
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Plant forhuman
TraditionalMedicine
Jamu
Beauty
Jamu
Health
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Health & Medicine
Maapin = I forgive you
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Beauty & Cosmetic
Gantengin = Make you handsome
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2. Forest Potency in EastKalimantan
2. Forest Potency in EastKalimantan
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1. About 35,000-70,000 of2,500,000 speciestraditionaly use and availablein markets globaly (Gettkant& Schafer, 2003 dan Mukerji1997)
2. 50% of drug from naturalresources(Gurib-Hakim, 2006)
Naturalsource ofMedicine(Global)
2. 50% of drug from naturalresources(Gurib-Hakim, 2006)
3. 80% world population indeveloping contries dependon traditional medicine indaily life (WHO, 2002)
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Indonesia 1300 sp known asmedicinal plants
Natural source ofMedicine (Indonesia)
1300 sp known asmedicinal plants
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ForestResources
Dayak (Native people)
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Food source
Local andexotic
fruit ???
Local andexotic
fruit ???
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Medicine source
Pasak bumi(Eurycoma longifolia)
Nature Viagra
LasatLasat//LangsatLangsat((LansiumLansium domesticumdomesticum))
MalariaMalaria
Ketikokng((Arcangelisia flava)Malaria and liverMalaria and liver
Pasak bumi(Eurycoma longifolia)
Nature Viagra
LasatLasat//LangsatLangsat((LansiumLansium domesticumdomesticum))
MalariaMalaria
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Screening medicinalplants (2007) Cosmetic
Anti Malaria
72 Species(West Kutai)
Anti inflamamtion
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Sungai Wain (Bpp)25 Species (Lab Forest
Prod Chem) (2011)
Sungai Wain (Bpp)25 Species (Lab Forest
Prod Chem) (2011)
Sungai Wain (Bpp)25 Species (Lab Forest
Prod Chem) (2011)
Etlingera balikpapamensis(new species by Poulsen)
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Tanjung Pinang, MuaraAndeh, Menamang Kiri &
Kanan, Tatung Villages37 Jenis (Diabetic &
colesteroll, Noorcahyati, S.Hut
(KSDA, Samboja), 2010/2011
Tanjung Pinang, MuaraAndeh, Menamang Kiri &
Kanan, Tatung Villages37 Jenis (Diabetic &
colesteroll, Noorcahyati, S.Hut
(KSDA, Samboja), 2010/2011
Tanjung Pinang, MuaraAndeh, Menamang Kiri &
Kanan, Tatung Villages37 Jenis (Diabetic &
colesteroll, Noorcahyati, S.Hut
(KSDA, Samboja), 2010/2011
Piper crocatum (anti diabet)
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Malinau ResearchForest, (Malinau)
132 Jenis (Yanti Yanti DwiRahayu, Tesis S2 (Forestry
Faculty, UNMUL)
Malinau ResearchForest, (Malinau)
132 Jenis (Yanti Yanti DwiRahayu, Tesis S2 (Forestry
Faculty, UNMUL)
Lepesso/Limpasu (anti diarrhea)
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Berau Research Forest40 sp (Forestry
Faculty, UNMUL) 80%fungi (2015)
Berau Research Forest40 sp (Forestry
Faculty, UNMUL) 80%fungi (2015)
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3. Results and Products
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Research on WoodResearch on Wood
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Screening of more than 100Indonesian medicinal plants forcosmetic & anti cancer in B16
melanoma cellsHeartwood
Sapwood
Arung et al. (Journal ofWood Science 2005:51:520-525)
Preparative HPLCSilica Gel Coloumn
Arung et al. (Journal ofWood Science 2005:51:520-525)
Artocarpin ( 1 ), cudraflavone C ( 2 ), 6-prenylapigenin( 3 ), kuwanon C ( 4 ), norartocarpin ( 5 ), albanin A ( 6 )artocarpanone ( 7 ), artocarpesin ( 8 ), cudraflavone B( 9 ), brosimone I ( 10 ), norartocarpetin ( 11 )
Arung et al. (J Nat Med 2009)
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Structure of Isolated compounds
Isoprenyl moiety
OHO
OH O
OH
OH
O
O
H3CO
OH
OH
OH
O
O
HO
OH
OH
OH
1
2
O
O
HO
OH
OH
OH
O
O
HO
OH
OH
OH
4
O
O
H3CO
OH
OH
OH
O
O
HO
OH
OH
OHO
O
HO
OH
OH
3
Evaluate the cytotoxicity effect onB16 melanoma cells
OHO
OH O
OH
OH
OHO
OH O
OH
OH
8
11
O
O
HO
OH
OH
OH
5
O
O
HO
OH
OH
OH
6
O
O
H3CO
OH
OH
OH
7
O
O
HO
OH
O
OH
10
O
O
O
OH
OH
OH
9
Arung et al. (Planta Med 2006: 72:847-850& Chem Biodiver 2007 : 4: 2166-2171)
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Skin cancer
Breast cancer
Neck cancer
Liver cancer
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CompoundCytotoxicity
IC50 (mM)
T47D HepG2 HSC-2 B16
Artocarpin (1) 12.6 8.6 15.8 10.3
Norartocarpin (5) 12.4 8.9 11.3 7.8
Table 2. Cytotoxicity of isolated flavonoid from wood of Artocarpusheterophyllus on some cancer cell lines
Cudraflavone C (2) 47.9 19.3 42.7 9.2
Albanin A (6) 59.3 51.6 58.6 84.7
O
O
H3CO
OH
OH
OH
1 2
O
O
HO
OH
OH
OH
O
O
HO
OH
OH
OH
5
O
O
HO
OH
OH
OH
6
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Compound CytotoxicityIC50 (mM)
Artocarpanone (7) 122.2
Norartocarpetin (11) >209.7
2’, 4’-dihydroflavone (12) 114.7
Morin (13) 170.0
Table 3. Cytotoxicity of non prenylated flavonoidon B16 melanoma cells
O
O
H3CO
OH
OH
OH
OHO
OH O
OH
OH
7
OHO
OH O
OH
OH
11 O
O
HO
OH
OH
OHOH
13
O
O
OH
OH
12
Cytotoxicity > 110 (mM) Arung et al. (Biol Pharm Bull2006: 29:1966-1969)
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Table 4. Cytotoxicity of prenylated flavonoid withone prenyl moiety on B16 melanoma cells
Compound CytotoxicityIC50 (mM)
6-prenylapigenin (3) 32.5
Albanin A (6) 87.4
Artocarpesin (8) 93.2
O
O
HO
OH
OH
3
OHO
OH O
OH
OH
8
O
O
HO
OH
OH
OH
6
Cytotoxicity 80-95 (mM)Arung et al. (Letter in DrugDesign & Discovery 2010 : 7in press)
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Table 5. Cytotoxicity of prenylated flavonoid with2 prenyl moieties on B16 melanoma cells
Compound CytotoxicityIC50 (mM)
Artocarpin (1) 10.3
Cudraflavone C (2) 9.2
Kuwanon C (4) 14.2
Norartocarpin (5) 7.8
Cudraflavone B (9) 12.5
Brosimone I (10) 10.7
O
O
H3CO
OH
OH
OH
1
O
O
HO
OH
OH
OH
Brosimone I (10) 10.72
O
O
HO
OH
OH
OH
O
O
HO
OH
OH
OH
4
O
O
HO
OH
OH
OH
5
O
O
HO
OH
O
OH
10
O
O
O
OH
OH
OH
9
Arung et al., (Fitoterapia 2010 :81 : 120-123)
Cytotoxicity <15 (mM)
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Table 6. Cytotoxicity of prenyl moieties & positivecontrols on B16 melanoma cells
Compound CytotoxicityIC50 (mM)
2-methyl-2-pentene (14) >2,000
3-methyl-2-butene-1-ol (15) >1,200
Vinblastine (+ control) 50.0
Carmustine (+ control) 120.0Carmustine (+ control) 120.0
5-Fluorourasil (+ control) 240.0
HO
14
15
14
15Carmustine
Cytotoxicity >1000 (mM)
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Sub-G1 apoptosis assay,DAPI staining, and Western blot
Apoptosis mechanism
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www.cellsignal.com
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www.cellsignal.com
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DAPI Staining
Control Treated with 12.6 µM Artocarpin
Apoptotic cells
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Sub-G1 Apoptosis Assay
Control Artocarpin 5.7 µMControl Artocarpin 5.7 µM
Artocarpin 12.6 µM Artocarpin 20 µM
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Western blot results
Control
Control DMSO
DMSO
5.7 12.6 20H2O2
H2O2 5.7 12.6 20
Artocarpin (µM)
Artocarpin (µM)
Artocarpin (µM)
A
C
B
cleavedcaspase-3
cleavedcaspase-8
Control
Control DMSO
DMSO
H2O2
H2O2
5.7
5.7
12.6
12.6
20
20
Artocarpin (µM)
Artocarpin (µM)D
C
β-actin
caspase-10
Caspase 9 ???
Arung et al. (Journal Natural Medicine2010) & Indonesian Patent 2007
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Control DMSO H2O2 (0.07%)
ΔΨm analysis membrane potential)
Artocarpin 5.7mM Artocarpin 12.6mM Artocarpin 20mM
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The number of prenyl moiety
OHO
OH O
OH
OH
A. Heterophyllus fruit
Enhanced thecytotoxicity
effect onsome cancer
cell lines
O
O
H3CO
OH
OH
OH
potent to be developed asbreast cancer agent with
extrinsic pathway
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The isoprenylated flavonoid
O
O
H3CO
OH
OH
OH
potent to bedeveloped as breastcancer agent withextrinsic pathway
A. Heterophyllus fruit
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Research on LeafResearch on Leaf
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Exploration of medicinal plant of EastKalimantan for hepatic disease (2008-2009)
Tahongai (Kleinhopia hospita)
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Rp. 0
Products 1#
Tahongai leaf (traditionalyfor liver/hepatitic dissease)
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Cytotoxicity onHepG2 cells
Antioxidant
Arung et al., 2009 (J Acupunc Meredian Study)
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O
O
OH
HO
O OH
OH
OHOH O
OH
O
O
CH3CH3O OH
21
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O
O
OH
HO
O OH
OH
OHOH O
OHO
O
CH3CH3O OH
Activecompounds
www.abihira.comCV. Abihira herbal centre
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Rp. 95.000/box
($ 7.6 )www.abihira.com (adopteddan developed by small scaleindustru name : CV. Abihira \)
Rp. 95.000/box
($ 7.6 )
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Effect on public welfare
1. Job opportunity2. Increasing economic value for people3. Health function for people
Job opportunity Economic value
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Future herbal products
Student in Labo to make herbal products
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Exploration of medicinal plant of EastKalimantan for cosmetic (2010-2012)
BLN RSN DK
Reg.Paten2012
Reg.Paten2011
SPLBlbn
SLP BTKMKD
Bedak dingin
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Products 2#
Rp.2.000/pack
(1 ball = 1 grm)
Rp.2.000/pack
(1 ball = 1 grm)
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Anti tyrosinase, antioxidant, melanin
inhibitor, cytotoxicity,anti acne tested !!!!
Anti tyrosinase, antioxidant, melanin
inhibitor, cytotoxicity,anti acne tested !!!!
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Exploration of traditionalcosmetic from native people inKalimantan
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How to use traditional cosmetic
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E. Triplinerve(Arung, et al. 2012; J AcupMer stud)
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E. Triplinerve(Arung, et al. 2012;J Acup Mer stud)
E. Triplinerve(Arung, et al. 2012;J Acup Mer stud)
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Melanin inhibition(Microscope image, 100x)
Rambai Sungai(Sonnaratiacaseolaris)
Rambai Sungai(Sonnaratiacaseolaris)
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Luteolin 7-O-glucoside
Arung et al., 2015 (Journal ofApplied Pharmaceutical Sciences)
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Reg Paten
Rp. 20.000/box(5 grm)
($ 1.6)
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Training for House wife in making Bedak Dingin (traditionalcosmetic), Semoi Village, East Kalimantan
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Products 5# Future Product
Collaborate with PT. MartinaBerto (Marta Tilaar Group)
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Cha
ngin
g of
ski
n w
hite
ning
(uni
t)
Skin whitening effect after 4 weeks use of Cream
N = 32 person
Cha
ngin
g of
ski
n w
hite
ning
(uni
t)
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Skin Moisture effect after 2 weeks use of Cream
Cha
ngin
g of
ski
n m
oist
ure
(uni
t)
N = 32 person
Cha
ngin
g of
ski
n m
oist
ure
(uni
t)
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Research on FruitResearch on Fruit
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Exploration of forest fruit of East Kalimantanfor cosmetic (2013)
Lai (Durio Kutajensis)
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Products 4#
Cosmetic ???
Future Product
Arung et al., 2015, Trop J Pharm Res
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Research on Animal productResearch on Animal product
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Exploration of Stingless bee of in KRUS forest foranti cancer & anti bacterial (2013-2014)
www.google.com
Syafrizal, 2014
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Products 3# Future product Ti = Trigona insicaTf = Trigona fuscibasisTt = Trigona balteataTa = Trigona apicalis
In Krus, Samarinda(Rp. 75.000-90.000/aqua bottle(300 ml) or $ 6 Product to be sold
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Ti = Trigona insicaTf = Trigona fuscibasisTt = Trigona balteataTa = Trigona apicalis
Cell line : KATO (Gastric), SW620 (Colon), HepG2 (Liver), ChaGo-I (Lung), BT474 (breast)
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Concentration : 20 ug/ml
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Antimicrobial ActivityTi = Trigona incinsaTf = Trigona fuscibiscaTt = Trigona balteataTa = Trigona apicalis
10
15
20
25
Propolis
250ppm
500ppm
750ppm
250ppm
500ppm
750ppm
250ppm
500ppm
750ppm
250ppm
500ppm
750ppm
(+) P. Ti P. Tf P. Tt P.TaCandida albicans 25 10,4 13 15,4 11,3 12,6 14,8 10,8 11,2 12,7 10,3 11,4 13,3Propionibacterium acne 25 10,6 11,5 13,7 10,5 12 15,1 10,4 12 13,6 9,4 10,8 11,7Streptococcus mutans 25 11,1 13,2 14,4 11,5 13,1 13,5 11,3 12,3 14,5 8,4 10,5 11,2S. thypii 25 10,6 11,5 12,7 11,7 11,8 15 10,2 12,1 13,8 10,2 10,7 11,7E.coli 25 10,9 12,3 13,7 11,9 12,3 14,8 11,7 12 13,9 8,9 9,7 10,8
0
5
10
mm
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PatenRegistration
Results
Publication
Some internationaljournal such as :Fitoterapia, J. NatMed, J. Wood Sci, Chem&Biodiv, Naturforschung,Drug Design &Discovery, PlantaMed, Food Chem, NatProd Comm, etc
5 RegisteredPatents (National)based on forestresources
Some internationaljournal such as :Fitoterapia, J. NatMed, J. Wood Sci, Chem&Biodiv, Naturforschung,Drug Design &Discovery, PlantaMed, Food Chem, NatProd Comm, etc
5 RegisteredPatents (National)based on forestresources
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4. Remarks
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Together isbetter
Together isbetter
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A. Prof. Kim Young-Ung (Daegu Haany Univ,, South Korea)B. Prof. Tohru Mitsunaga (Gifu Univ, Faculty, Japan)C. Prof. Hiroya Ishikawa (Fukuoka Women’s University, Japan)D. Prof. Hiroyuki Tanaka (Kyushu Univ, Pharmacy Faculty, Japan)E. Dr. Kuniyoshi Shimizu (Kyushu Univ, Agriculture Faculty, Japan)F. Dr. Keisuke Yoshikawa (Saitama Medical Univ, Japan)G. Dr. Laifa Hendarmin (UIN, Fak Kedokteran, Indonesia)H. Dr. Ahmad (Stem Cell & Cancer Institute, Kalbe
Farma, Indonesia)I. Dr. Arief (UGM, Fakultas Farmasi, Indonesia)J. KMUTT, ThailandK. Kasertsat University, ThailandL. Chulalongkorn University, ThailandM. Prince of Songla Univ, ThailandN. Dr. Huseyin E. (Kafkas University, Turkey)O. University of Texas at El PasoP. Dr. Mark R (Bangor University)
Collaborators
A. Prof. Kim Young-Ung (Daegu Haany Univ,, South Korea)B. Prof. Tohru Mitsunaga (Gifu Univ, Faculty, Japan)C. Prof. Hiroya Ishikawa (Fukuoka Women’s University, Japan)D. Prof. Hiroyuki Tanaka (Kyushu Univ, Pharmacy Faculty, Japan)E. Dr. Kuniyoshi Shimizu (Kyushu Univ, Agriculture Faculty, Japan)F. Dr. Keisuke Yoshikawa (Saitama Medical Univ, Japan)G. Dr. Laifa Hendarmin (UIN, Fak Kedokteran, Indonesia)H. Dr. Ahmad (Stem Cell & Cancer Institute, Kalbe
Farma, Indonesia)I. Dr. Arief (UGM, Fakultas Farmasi, Indonesia)J. KMUTT, ThailandK. Kasertsat University, ThailandL. Chulalongkorn University, ThailandM. Prince of Songla Univ, ThailandN. Dr. Huseyin E. (Kafkas University, Turkey)O. University of Texas at El PasoP. Dr. Mark R (Bangor University)
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Labo Members
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Thank you very much for your kind attention