International Seminar

HINDU IJI{DONESIA UNIVERSIT}'

Jl. Sangalangit. Tembau. Penatih. Denpasar - Bali wrvw.unhi.ac.id

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TABLE OF CONTENTS

Preface

from

Chairman of

Editorial

Committee Remarks

from R*ctor

Table of Contents Keynote Speakers

Nanotechnology

Applications in

Delivering

Ayurvedir

Drug Curcumin &

Natural

Compounds

for

Better Effectiveness and Its Economic

Impact

}'asiirva n

i

Pa thak..."...

The

Contribution

of Balinese

Traditional

Healing on

the

Sustainabtre Development of

Bali

Nyoman Adiputra...

Concept af Healing in'Ayurveda

-

^{Time Tested} Ancient Wisdom of Medicine

The Past is

Alivs

in The

Present

Folk Healing Practices Among The

Filipinos

Lahaina Sue C. Azarcon...,., Parallel Speakers

Froduction

of itriediciiial Cumpounds

in

PIants

i

Gede Ketut Adiputra...,...

D^*.i 1., rr^l^ :* r-I^^Ilt-

a dirrtrj l\Ua€ lll a ICdtLll

Self Hypnosis Reduce Pain

tabor

and

tiftingtabor

Ni Wayan Annini...

Hindu Bioetics: Healthy Philosophy

in

Dasaaksara

Religion as

the

Cure

for

Mental

Disorder in Bali

I Wayan Budi Utam4 I Wayan MartJra, I Gusti Agung Paramita...

i1i V

vlI

13

20

z'1

JD

49

60

69

ISBN. 978-602-61920't)-4

International

Semina$ Hindu ^I ndonesia

University

The Conr:ept of the Healing in Region, Culture, Health Scinces and the Economital Prospective

PRODUCTION OF I4EDICINAI COMPCIUNDS IN PLANTS

I 6ede Ketut

Adiputra

dr;qede-a ii ipurra@tyaho o. co. i d

Department of tsiology, Faculry of Natural Science, UniversiW of Hindu Indonesia ^Denpasar'

Atrstract

fJnce planl-s anchoi: its raot into the soil, they stay

in

the place forelrer albeit varinus environmentai conditions ^are exposed to them. The abilily of plants to solve environmental conditions is amazing and rise que.stion of how the planls reguiate physiological mechanism under the environrrrental stress. Ba..se on the fact that plants are autnl.rophic,

it

is ^very likely tirat piants produce speciiic comporind lo aileviaLe stress.

It

is ^alsr: hypothesized lhat canCiCaie f'or these compcunils are criginated from priitar.i' metabclites syrtlresizeC by plants

in

chloroplasi;. So, sp-recific compounds produced by plants to alleviate stress condlrions are con:moniy known as secondaty meraboiiles. iliversities oi these specific compout'rds are ellormous, thousands of it has been fbund. Those various cotrpoutrds are lhen grouped into terpenoids, alkaloiris and phenolics compounds. Some of the compounds harre been successluliy used lo alleviate humatr diseases. More importantly, Indonesia as a

lropical country is reported to have a haif of world plants.species. If those specific compounds a.re prr:,duced hy specilic plants.species, lndonesia is thet'etble ha.s a tremendotts sollrce of secondaryr metaboiltes rvhich could be use to ease medicinal problems. Howeve4 only .sci.;ic plan',s ai-c ali-ea*.ly liiior,','ri as mcJicinal ^plarirs, so, l^tii-thcr ccmpi'chcnsivc stuily is stili recluired to ease medjcinal problems.

Key wo rds: Bi o.s,vnth esi s, environm en t, medi cin ai plan Ls, s eco trdary m etab ol ites.

INTRODUCTION

Human survival depends on the sustainability of organic cotnpounds synthesized ^by plants.

This is because iood as a ^sor.rrce of energ;r

fnr

hr-tmans heing ^r:at: nnly ^fus prt-ldtt.ed

l:y

plants, Tire study of the biosynf.hg5is of organic compounds

in

plants has been done

tbr

centuries ^atrd continues to [his rlay. Unlike animals ^and ]luman being, plants are a-ble to produce *rganic material because they have organelles known as

chlnroplast.

T'itis organelle is

the

sites where plants synthesize organic compounds usine ^enerp;y fiom sun Iight. The main prodncts of this process are carbolryrirates, iats, proieins and nucieic acids. This compcuttri is mainiy used by piatrts for growth antl reproduction. Therefore they ^are classified as primary rnetabolites. ^{The same} compounds are also u.sed by aninrals and humans for growth aud energy sources, but because they do not have chlor'uplasl, alliiriais atrrj iitiurarrs depetid ^orr plairts fur

tlieii'

footi.

Iii adeiiiioii ii: priinary rlrelai:erlites, 6ilaiils ^also proiluce a vai-iety uf coiripouiltis ihai are

itni

directly related to growth and reproduction. These eotnpouncls are then classified ^as secondary

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(l

Gede KetutAdiputral

metabolites. This secondary rnetabolite is also an interesting subject for a lorig lirne, especially in medicine [Pavarini et ^{al. 2012}

j,

Some argue that secondary rnetabotrites are produced hy plants tn nvercome the distut"hance nf their envrronment or as a tool that can help ^sper-'ies preservation.

F'or plants, this material is very important because since the piant stuck his roots on the ground,

it

rvilI remain in thal plar:e 1'oreven J'he environmetrt, where the plant is located, can

turn

out

t*

Lre verv danqerous fnr its growth, both in ternis of biotic and abiotic stress. Without the abilitSr lo cope

with

the dangerous situation, the existence of plants ir-r the place rruill be threatened with exiinction, ?hereiore ^pianLs also prociuce compoutttis thai are not ciireciiy reiated to Srorn/th and rep rnduction call ed secondar5, rnetabolites.

Unlike plants;, humatrs and anitnals can move to avoiil dangerous environments, but they can also experience dangerous situations, both biotic and abiotic. Eacteria or viruses, which can cause disease in Iiuir;aiis, can be anywhere. Like-vi;ise, -weatlic.r aiid chei'irical ciranges cait tlireaier: iruiriair

health.

Horvevet, hutnans and animal could not synthesize

their

own secandary metabolites, as

the planls do. Therefore, humans depend ou plants not only, far energy and gro,,vtlr, but also

fbr

.-.,ri-i-^

It has norv bccn

rclordcd

that thcusands of'sccondari,' rnetabclite compoilnds prcduce d h3z

planls.

For humans and animals, these secondary metabolites have varying effect. Son:e plants produce secr:ndary me[aholites that can be taxic to ]lurnans. These ccmpounds belong to the group

tf

alkalrrids, sttch as nicctine, caffeine, marphine and cocaine producecl b;r tobacco plants, coffee, cannabis and coca. Other compounds produced hy plants have a

bitter

taste. These compounds belong to terpenoid groups, such as mint, taxol, r*bber and re.sirrs. Compounds

tlat

also irelong to terpenoid groups are cvanogenic gl.vcosides and cardiac glvcosides, If cyanogenic glycosides which praduced by Passiflora plant are consumed by animals or hurrrans then these compounds

will tuni

into cyattide in the liody and

wili

endanger ihe sai'ety of irumans anci animals. Cardiac giycosiries produced by Digitalis plants" I'his compound is very famous because

it

^can affect the work of the heart. Plants also produce secondary nretaboli[es that produce atlracLive cclors for animals and l:utiiatis. The purpuse

oipiaitls

tu produce ihis utriiipuund is to aitract;iiiirriais aiid liuiriaiis io heip pollination

or

disperse seeds so that tlte sustainabilify of tire plant species is preserved. ^'l'hese compounds are classified in Phenolic groups. Exarnples of compounds 1:elorigingto this group are flavonoids (coloring grapes), taiiuins anC !igrr:ns. The ccrnpound'"vhiL'h also irrcliides phcrrulic ^i.s salicylic acid which ^is thc main component of painkiliers aspirln. This salicylic acid is produced by wiilow planh;.

DISCU.SSION

Biosynthesis of secondary metabolites

in

plants

Secandary metabolites

in plants are

produced

from prinrary

metabolites synthesized

primarily

in chl*roplasts frunr in*rganic compounds using energy frnm sunligtrl. The metabclic pathway to produce secondary metaholites begins

with

the main route: _[1J glycolysis producing pyruvic acirl, [2) conversion of pyruvic acid to acetyl-koa and [3] ^{the l(reb cycle.}

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^{6ede KetLrt Adiputra]}

i!\ I

ir.,7 r,. -

''l

-i

I i .',.. ^r

\.i . ,, ri

ru*"tr'

-".fu-l&* r*4-1.,:{!}t* j6-a ?\y.r\':tr..}noi"-,-^,/.,,,, j

- ^{,*,, *^., ,.,.,,}

,*Jllr,

r'rffa d'r

\ii ' i'

:,,..,.,,.j,.,,,"1 ,,*.,,)I., :-'ill"":l -=---*

.5-,\f(&{. tr:r-..*-.Lr.tnr3t _*.. }l -.- ., ,.s.n

- . Lr_.r ^-i- r,,,.,,

strr ir: B i" i,,,

l.,.dilxlq. t.r$ir (-"rl.r^._ L,ru!{ir

Figure 1. Amino acids as the precursor for secondary metabolite are produced from the primary rnetabolite, glucose [Kabera ^{et al} 2014j.

II Ph*r5yBh6is +

Frythire 4-dm$hafr

Plxrrplutni,lp;rrrrirt

sllu(l\tllRr c,lLlx):! [lt:'r,lB{)l,ts\t

Figure 2, The synthe sis of alkaloid, terp.rene and phenolic compounds fNcuhe and Van Staden 20151.

At

each stage of

this

glucose metabolism, arnino acids are produced which then become the precurscr fcrr secolldarlr metabolites. From sr-age 1 fgl]rcolysis], producs Shikinric ^{acid, r.trhlch} is tlien converted to amino acid phenylalanine, tyrosine and

triptopan.

From stage 2, mevalonic acid is produced. Amino acid originated from stage 3 [Kreir ^cycleJ includes: methionine, lysine,

arginine.

The antino acids that uroduced from

primary

nretabolism are presented

in

Figure ¹ fKaberaetal.2014]. AccordingtoNcubeandVanstaden[20lSj,seccrndarymetabolitesynthesize.s tronr glycolysis are mostly compounds that beiong to terpene groups. Phenolic compounds are firoduced from acetyl-CoA and alkaloid ^is produced f'rom Kreb Cycle [Fig.2J.

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^{Gede Ketut AdiputraJ}

Secondary

metabolites

as medicine

Secondary metabolites are essential tbr plant growth because they are useful for overcoming unfavorable envirotttnents and as a illeans of seif-dsfense. Secondary metabolites are also very irnpnt'tant for hurnan hea-lth her:au.se

it

cnuld determines the qrrali[z nf food, colnq flavoq aroma, anti-oxidants, anti-cance4 tension reductior"l, anti-sweliing, anti-microbial,

triggers the

body's def'ense systeln, lowe rs choleslerol etc. Ircirhaiya eIal. 2074). According to Wink (2 tt 151, secondary metAbglites pfgd1ted by plants ^are weil known fbr

their

toxic properties. Thcsc rnctaholites a.e usually cCIntaills all{alilid 0r terpene. Sonte of these conlpouhds has been extracted

,url ,o"J

in mcdern meciicines. This author indicated thai secandary metabolite *f this kind ^has specific target on human [Wink ^{2015, Tah. 1_J.}

Trrble 1.

Lilt

;ruti broactiliq.

oi;

te',r-ieleciire tertrrclnry mttaLrt,iit*r .',,"hith rre .tirphe,l nl i:t,l:rte tl cc,u:1:*itilils i+ mer-tricrlre

ll il:

elkat*tril t'A:. :+rper':itii iT I _J1 !-1{1,

Flaat5p*ci* $rb:tanrc {C!a*} l[r;dr r,f dril*r Prlprrt:e: .Lpplir atiol:.

..,,',+,..- '.'.i, ^. -i51:11 iryii6,i;::!15

_ r:r,,; .(. r L r.

a rTiirti;tii .:. ii"! i,.

i-.li;i lr':Ii iiilll: I r::i{?' :

i-- i; grell cci-;;:.'; l l; in rriii:oi ^!rrr'

r- ii; ^{g 111: r;1} 3r1 ;:;-- "'.r,- . r.r'ir lrri:l;l

aseitne L{}

r-tlstc1reiB€ fu*

r'aarptatk*iaffi

e&*&g&ocannabia*l (l.l dimrrir linea a&dsids {A)

lubc$affi$e {A) q{rtuidisd [A]

ca{f*iae {Al

actitatx !in" rhgEaeir autog*uix of,a4.C&R iah.rbhor uf Dhi tspoilouleraie

acti.;*tes TltC recept+r tuir,bit oai$$tr:brrtre aer*.sbh.

iEldbilse{ChR i8hidtrh'E ckeeels

o-hib* phoqho*eetenrt mrd edeaome recrytcrr

aaalgex.*

pm*qrmry*&ouaiorctir tuaoil, i&erxpy

*n*lgearc

*mm rherspy urrsci* rrlaxani

*su*rb'rlair :rimrlml esui Erefur€at {'airl:rtxra *urur*rurfe c*lchiciae f&l ^irh.ftits airmtrh:}* a**emhly

f.iillt i. L rrili

Pl.rut !trrit: lulr:tru<r i{- h::1 llsdr *1.{rritn ?rEa er riri:.{.nplicafic,l:

$.li,le.r s*gruius -*lg$sfti- Idlf*fa

{.r::r.ilrr:r-l-rt*n rorr

Gs]*x!*r+.: t* on*eii lo:a rorrtixm e*zrqlnan Pcpcter rou*rqftxrm Pir;x*sfi-qr** rat+xosr;m

Frieo;aryu:3eScrnit'*

Fqrrhrtna ryeera::crrhn ftmnu4$a i.*r-a4pi*s

Sr*rguin*r:n rmana'*r:ls 5e'aplr*riar gron;r

Iams &rer,ilhfia

ry5lteiaE {*}

.iligrtoxia {igcr;u {I}

romi*{Ai

galam*aras tAi

eupcculs Ai.{}

rosrpeilr (d) pbls**ti6auetA]

pilor.erpi::e{A}

€serrte {A}

rcaeryine {A}

carlplissim* tA) suateiu tfi

paclitasel {taxo!} iAi

i*itritElftr *h:mlr ialibir i\:*"s-'A1?hee iu&ib:ts !ia* dr*m*le a.ud reupt*k* of

*sr*dr{f,ali&* flurl d*pr*arue itt&isis AL'}IE inbihits &C&E a$o*rst sf ffd*sphine rectSaerE

inhibiti AC&E agw:siaf trAChE- prnten biosSuth*oir inhibimr inh:hle tktrpr** af arrradrc*alin

ialo p*sr4roaptic leicl*r

S1{-& intercnlai*r ia&iliu ld*'" K"-A?Fase

;nhrfu1; mrcp15fu6e drmsrerrblv

aaliar:h,l'i&a*ir he*rt r*auIEeiem,

enatrgelir: atiwnlaat

.{sheieer &-ca*mnt

. Akheiro{Eteafuo*El anelge:i*, &aIluciaogpl

.Alihrie*r a€&&ee!

glauecra:a treatuielr{

tu""xtosnul 6f asnebre ia&ctraru; mtir

h?erteEia teat$f,Et aal&:tcisial a$itiral haertiumffirim:1'

iueemrlberap

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^Gede KetutAdiputraJ

According to Wink _[2015J, all<a]oid compound are rarely found in traditir:nal medicine. Since t]ris traditional medicine usually apply extract,

il

bioactivity is almost not klrou"n. This particularly trecause extrart rontain various

fnrm

nf romporrnds. As shown

in

Tahle 2, rnode

rf

action for compcuud that produced hy medicinal plants are not specified _{{Tab. Z].}

Tirl:lt

l,

(-:'tiii..,r=r",i .,rl .llr).'r.i.. -:r,-,:5rli:.-lii:ri:j1-,1.,r:r.'-r:*ii lir:r':,Ji-:.-.:t:,i,:,111 ti-r--lrrl:.'.. ..r-.1

tireit p,.u;tii'e ittt*r':ic li+r:i

Ii{i- j:

^j.

Fiieuolics

-

ferp*noids

-

_!apouiul

'

Polvsarrhalitl*r ^-

( _{r', nleu{}

I;:tr'r'rcti+r;

'-

)Iedicira! Plaut Drug ,'-.,.-.... i-:i.)t a'irlfa,.ii? ^g:i,;

r ---.., : .-

,aL_\L'..rJ,. L-i._i':,L i'r': l]:1 .{ ii il;;l ;rrrtri'rr,;

,- i i jrr;.rl'i

i: lli.l' i...:.r ii:

.i it ilrlr"-,:':':;}iti: j:i? rii rri:;i"

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.t.; J'ti ;:i,' l,:z i,lat,:

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{, r,it,'r:jir: :.;irit a.'l l':-.,.r.!,.1r.-,,.-

a,,,r a,,,,r,, iO,,'i, f.'i,:.lr':i i.,tr::ti;,i.:".i.r;i,,-i

f i ^it : :i,i artii !.,, :it lii'i,,;

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+ .H

#

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t+

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+ +

+ +-

+ + +

+

++

*

#

*

-l.-i

+

+-+

-+

Factors aff'ected the biosynthesis of

medicinal

compounds in

plants

in planLs, production of secondary rnetabolites is used for a def'ense system and adaptatiorr h; tite envirofiirlei)1, The pi'udLtctiott is alt'ected Lry various ^f actor-s sucl"i as; LrioEie, a'uirrtic afiLl

filallt

growth factors. Biotic factors can be herbivores, l"lacteria or viruses that cause clisease in planls.

Ahiotic factors can be light, dryness, temperature, height of.place etc. l,Vhile the developrnent of

nlrntr ic.r,r irrr.'yn-l f^-ts^- ^--^-i-+^J,^,;+1, Il,.^ --^,^,+L ,.L^-^

l,luiib r) dlr ii,Lul licir ld( Liji (ii)SULtdiuii !ViLti iiiU SIU\Vtii iliial.'tc.

D:^l:^ f^^+^.,- UIULIL idlLUT 5

lleveral

['pes

^i:f- seciiildary metaboliie compounds inchide diterpines anil sesquiteri:ines produced by plants as a direct clefense agailist herbivore and microbial pathogens. Because

it

can be toxic or has a very unpleasant taste, then the animal

will

not consume it so that the plant is free from herbi"rore attack.

in

the eyent

sf

a bacterial c." heri:i',zsr-ous allaci{, the plant rn/ill increase the production of this compouttd so that its accumulation

will

increase in the plant _[Cheng et al., 2A07J"

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^{Gede Ketut AdiputraJ}

Altitude.

Flavonoids are a verr/ obvioris example showingthatthe production of secondarymetabolites

is

affected

by the altitude of the

site. Cornpounds belonging

to ihis

flavanoid group include:

Carotene, vilamin C, anthncyanin. These cr:mpnunc!.< r,rrere fcund higher in the nr:rthern regions compared to the southern regions []aakola and Mohtoia ^2010J. The increase in flavonoid levels is attributed by the responds of planls to coid environnrelrtal conditions.

Light,

temperature

and

drought

tinder

serious conditians, such as high tight intensity, high temperature and draught the plant canrrot con[inue

ils

growth un]ess

it

could produce compounds to alleviate the conditir:n.

These ettrrirontlental factors can Iead to producticn of excess erlergy

in

plants that resulted in the formation of reactive oxlgen" The.se reactive compounds can aciverseiy anect physioiogicai processes in plants. Therefbre under conditiotr of these environment, the

plantwill

increase the productiou of anti-oxidants i.e" flavonoids and phenolic acid [Ramakrishna et al.

2011].

Airiotic iaclor tha^t niay affe(t secorrrlary rnelaiioiite proriuctiu,n in piant is presenter"i in Fig. 3.

B ill(r

l$$usht. i loodflr.s

R*dlsfiBg i

I

tI

rlrrrrdt.sl rtl,rsr

llethruri(al rtr-tr!i

lfiiltrili*4 radialr'x

Fig. 3. ,Abiotic factors affected the production of secontiary metabolites.

It

is believed that piants have been used for medicine since hurnan civilization. Plant part that is used for traditional medicine may be root, flower, leaf or

fruit.

In the "Usada of Bali", the nutrti:er

of

reeorcled species used as uteilicirtal rnaterials anri has heen klrt.rr,vn scientificaliy is oniy about 60 species [Adiputra 2008J. This anrount is very small when

it

is compared

lvith

the existing plant species in Indrinesia which accounted for abou[ 170t]00 [one hundred ^and seventy nhousand] _ry*pes of pian'.s (Tjiirosoepoffio

20Ail.

rntT-r rt-t^Lr

{-r_r_tl LLt Jitl t ll

Fiatits appear

to

have a pi:iiosi:phy sirrrilar

to

hilniaiis, i.e. taking drugs ^-wirEn there

is

a

healtir problem. Howeve4 whereas humans look for drugs to alleviate diseases because they could

Eleat

^Csld

i\

/ls

Cldtlirg

Frrr*t

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.ll,irrlir rtrtrr riguatr

, 'f*rytr*Mr

,,' I

I+

,/l

{l

6ede Ketut Adiputral

not produce

it

plants

will

^rnake their own materials to alleviate health problems. Since secondary tnetabolite in planB; is species specific, potentially indonesia has various kinds ^af medicinal plants.

So, in arder to ease medicinal prohlem, Inrionesia should promole more !:esearclrer tn identify and subsequently conserve medicinal plants.

R.eferences

Adii:iitia

N. 2U08. 'l'anamatt

Sebagai Hahan 0bat, Menurut Lontar Usada Bali. Fakultas ffedokt"ran Llniversitas Udayana, Hali. Http://Wr,rrw.Scribd.Com/Doc

/927BZNB/File,

^{Download: 10} Mei 2012

Cheng AX, Lou ^YG, Mao YB, Lu S, Wang LJ, Chen XY

20t)7.

Plant terpenairl: Biosynthesis and ecoiogical functions. iournai of integrarive piant iriology 49 (21:17v-i86.

Irclrhaiya R, Kumar A, Yadav A, Gupta N, Kutnar S, Gupta N, Kumar S, Yadav V, Prakastrr A and Gurjar

H 2A74.

Metabolites

itt

plants and

its

classification, World

journal

of pharmacy and i.iirariiiacei; ^{Li ci: I st-- ie n r es 4}

[i

^{J : 2 I 7-3 0 5.}

]aal<ola L and Mohtola A 2010. Effect of latitude on flayonoid biosynthesis in plants. Plant, Cell &

Envirotrment 3 3 ^: 1 2 39- 1247 .

l{abel'aJl{,Se}nana[i,S{ussa,^.P.,Ile X2CI4.Plant.gecondli-yrnetal;olites:Biosl'nthesis,clussificafion,

funrtion

and pharmacological

properties.

_Journal of pharmacy and phannacology 2:

377-392.

Ncr:be B an,l ^V.an Stadetr

I

2015. Tllting planl metabsli."nr

f*r

impro.rer! rnetabolife hics5rnlhsrlt and enhanced human benefit. Molecules ?il:1261)8-12731.

Pavarini DP, Pavarini SP, Niehues M, Lopes NP 2t)12" Exogenous influences on plant secondary metabolite levels. Animal t-eed science and technology 176:5-16.

Ramakrishna

A

and Ravisliankar GA

2011.

Influences

of

ahiotic stress signals on seccndary meta-boiites in piants. Fiant signaiing & behavior

6[iij;1720-'173'1.

'l'jitrosoeporno _G. 2004. Taksonomi tumbuhan fSpermatophytal. Gadjah Mada University Press.

Wink M. 2015. Modes of Action of Herhal Medicines aud Plant Secondary Metabolites. A4editines

2 : 25i-286. rio i ;

i

0, 3 3 9 0 /medi ^{ci I r esz 0 3 02 5 1.}

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