2016 icb balikpapan - smujo.id · (arcangelisia flava) malaria and liver. screening medicinal...

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

Forest Biodiversityfor Medicine and Cosmetic

Enos Tangke ArungEnos Tangke Arung

ICSIBMU-Balikpapan, 14-16th January 2016

Laboratory of Forest Products ChemistryForestry Faculty, Mulawarman University

1. Introduction

2. Forest Potency in EastKalimantan

3. Results and Products

4. Remarks

Outline:

1. Introduction



4. Remarks

1. Introduction1. Introduction

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)

Recreation

Carbon stock

Economic source

Loss of Forestbiodiversity :

Palm oil plantation

Coal mining

Coal mining effect ?

InternationalNGOLocal NGO

LocalGovernment

ForestPolice

Scientist

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

Plant forhuman

TraditionalMedicine

Jamu

Beauty

Jamu

Health

Health & Medicine

Maapin = I forgive you

Beauty & Cosmetic

Gantengin = Make you handsome

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)

Indonesia 1300 sp known asmedicinal plants

Natural source ofMedicine (Indonesia)

1300 sp known asmedicinal plants

ForestResources

Dayak (Native people)

Food source

Local andexotic

fruit ???

Local andexotic

fruit ???

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

Screening medicinalplants (2007) Cosmetic

Anti Malaria

72 Species(West Kutai)

Anti inflamamtion

Sungai Wain (Bpp)25 Species (Lab Forest

Prod Chem) (2011)


Prod Chem) (2011)


Prod Chem) (2011)

Etlingera balikpapamensis(new species by Poulsen)

Tanjung Pinang, MuaraAndeh, Menamang Kiri &

Kanan, Tatung Villages37 Jenis (Diabetic &

colesteroll, Noorcahyati, S.Hut

(KSDA, Samboja), 2010/2011









Piper crocatum (anti diabet)

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)

Berau Research Forest40 sp (Forestry

Faculty, UNMUL) 80%fungi (2015)

Berau Research Forest40 sp (Forestry

Faculty, UNMUL) 80%fungi (2015)

Research on WoodResearch on Wood

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)

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)

Skin cancer

Breast cancer

Neck cancer

Liver cancer

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

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)

Table 4. Cytotoxicity of prenylated flavonoid withone prenyl moiety on B16 melanoma cells


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)

Table 5. Cytotoxicity of prenylated flavonoid with2 prenyl moieties on B16 melanoma cells


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)

Table 6. Cytotoxicity of prenyl moieties & positivecontrols on B16 melanoma cells


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)

Sub-G1 apoptosis assay,DAPI staining, and Western blot

Apoptosis mechanism

www.cellsignal.com

DAPI Staining

Control Treated with 12.6 µM Artocarpin

Apoptotic cells

Sub-G1 Apoptosis Assay

Control Artocarpin 5.7 µMControl Artocarpin 5.7 µM

Artocarpin 12.6 µM Artocarpin 20 µM

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

Control DMSO H2O2 (0.07%)

ΔΨm analysis membrane potential)

Artocarpin 5.7mM Artocarpin 12.6mM Artocarpin 20mM

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

The isoprenylated flavonoid

O

O

H3CO

OH

OH

OH

potent to bedeveloped as breastcancer agent withextrinsic pathway

A. Heterophyllus fruit

Research on LeafResearch on Leaf

Exploration of medicinal plant of EastKalimantan for hepatic disease (2008-2009)

Tahongai (Kleinhopia hospita)

Rp. 0

Products 1#

Tahongai leaf (traditionalyfor liver/hepatitic dissease)

Cytotoxicity onHepG2 cells

Antioxidant

Arung et al., 2009 (J Acupunc Meredian Study)

O

O

OH

HO

O OH

OH

OHOH O

OH

O

O

CH3CH3O OH

21

O

O

OH

HO

O OH

OH

OHOH O

OHO

O

CH3CH3O OH

Activecompounds

www.abihira.comCV. Abihira herbal centre

Rp. 95.000/box

($ 7.6 )www.abihira.com (adopteddan developed by small scaleindustru name : CV. Abihira \)

Rp. 95.000/box

($ 7.6 )

Effect on public welfare

1. Job opportunity2. Increasing economic value for people3. Health function for people

Job opportunity Economic value

Future herbal products

Student in Labo to make herbal products

Exploration of medicinal plant of EastKalimantan for cosmetic (2010-2012)

BLN RSN DK

Reg.Paten2012

Reg.Paten2011

SPLBlbn

SLP BTKMKD

Bedak dingin

Products 2#

Rp.2.000/pack

(1 ball = 1 grm)

Rp.2.000/pack

(1 ball = 1 grm)

Anti tyrosinase, antioxidant, melanin

inhibitor, cytotoxicity,anti acne tested !!!!

Anti tyrosinase, antioxidant, melanin

inhibitor, cytotoxicity,anti acne tested !!!!

Exploration of traditionalcosmetic from native people inKalimantan

How to use traditional cosmetic

E. Triplinerve(Arung, et al. 2012; J AcupMer stud)

E. Triplinerve(Arung, et al. 2012;J Acup Mer stud)

E. Triplinerve(Arung, et al. 2012;J Acup Mer stud)

Melanin inhibition(Microscope image, 100x)

Rambai Sungai(Sonnaratiacaseolaris)

Rambai Sungai(Sonnaratiacaseolaris)

Luteolin 7-O-glucoside

Arung et al., 2015 (Journal ofApplied Pharmaceutical Sciences)

Reg Paten

Rp. 20.000/box(5 grm)

($ 1.6)

Training for House wife in making Bedak Dingin (traditionalcosmetic), Semoi Village, East Kalimantan

Products 5# Future Product

Collaborate with PT. MartinaBerto (Marta Tilaar Group)

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)

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)

Research on FruitResearch on Fruit

Exploration of forest fruit of East Kalimantanfor cosmetic (2013)

Lai (Durio Kutajensis)

Products 4#

Cosmetic ???

Future Product

Arung et al., 2015, Trop J Pharm Res

Research on Animal productResearch on Animal product

Exploration of Stingless bee of in KRUS forest foranti cancer & anti bacterial (2013-2014)

www.google.com

Syafrizal, 2014

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

Ti = Trigona insicaTf = Trigona fuscibasisTt = Trigona balteataTa = Trigona apicalis

Cell line : KATO (Gastric), SW620 (Colon), HepG2 (Liver), ChaGo-I (Lung), BT474 (breast)

Concentration : 20 ug/ml

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

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

4. Remarks

Together isbetter

Together isbetter

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)

Labo Members

Thank you very much for your kind attention

2016 icb balikpapan - smujo.id · (arcangelisia flava) malaria and liver. screening medicinal...

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