Malay traditional medicine

TECH MONITOR Nov-Dec 2006 37

Special Feature : Traditional Medicine: S&T Advancement

Malay traditional medicine

An overview of scientific and technological progress

Jamia Azdina Jamal

This article describes the principal practices and status of scientific research anddevelopment (R&D) of Malay traditional medicine. An example of a systematic scien-tific study on Labisia pumila var. alata illustrates how a traditional preparation hasbeen transformed through research into a modern pharmaceutical dosage form.Several business opportunities and strategies are suggested for small and mediumscale enterprises (SMEs) that are interested in traditional medicinal products, par-ticularly herbal products. The article concludes that industry must use a holisticapproach to comply with consumer expectations of herbal products.

Dr. (Ms.) Jamia Azdina JamalDepartment of Pharmacy

Faculty of Allied Health SciencesNational University of Malaysia

Jalan Raja Muda Abdul Aziz53100 Kuala Lumpur, Malaysia

Tel: (+60-3) 4040 5303Fax: (+60-3) 2698 3271

E-mail: [email protected]

aggregated to US$ 80 billion. In thesame year, the Malaysian market fornatural or herbal products, medicinalplants and aromatic plants includingaquatic animals was estimated at RM4.6 billion with an annual growth pro-jection of 15-20 per cent.

Malaysia has great potential todevelop her abundant natural resourc-es to increase the market based onherbal products. This is evident from a1935 report1 that in peninsular Malay-sia alone there are about 550 generaof tropical plants, containing over 1,300species possessing medicinal values.Of these, several are medicinal plantsyielding clinically useful drugs, someof which are listed in Table 1. However,these plants have not been extensive-ly cultivated or exploited here. Someexamples of popular Malaysian plants

Introductionhe World Health Organization(WHO) defines traditional medi-cine (TM) as “health practices,

approaches, knowledge and beliefs in-corporating plant, animal and mineral-based medicines, spiritual therapies,manual techniques and exercises, ap-plied singularly or in combination, totreat, diagnose and prevent illnessesor maintain well-being” (WHO, 2003a).

The popularity of, and demand for,medicinal plants as health supplementsor for medicinal purposes have beenincreasing worldwide. The renewed in-terest of knowledgeable consumerscould be associated with increasing in-formation and availability of herbal sup-plements globally. The demand can bedemonstrated statistically. In 1999 alone,sales of herbal products worldwide had


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38 TECH MONITOR Nov-Dec 2006


currently undergoing extensive re-search are the male aphrodisiac Eury-coma longifolia Jack. (tongkat ali), La-bisia pumila (kacip fatimah), Androg-raphis paniculata (hempedu bumi),Orthosiphon stamineus (misai kucing),Centella asiatica (pegaga), Phyllan-thus niruri (dukung anak), Momordicacharantia (peria) and others.

This article briefly describes thepractice of traditional medicine by theMalay community, which comprises themajority of the Malaysian population,and the application of science and tech-nology in transforming traditional prep-arations into modern pharmaceuticaldosage forms. It also includes a scien-tific study on a Malay traditional medi-cine, Labisia pumila var. alata. It coversthe standardization of herbal productsto provide information and understand-ing of the requirement and significanceof the principal elements. It also makesseveral suggestions, based on learn-ing experiences, for local and interna-tional small and medium scale enter-prises (SMEs) that are interested in theindustry of traditional medicinal prod-ucts, particularly herbal products.

HistoryThe principles of Malay traditionalmedicine are generally based on theArabic Unani medicine and Galenicphilosophy. However, it is also influ-enced by other practices of Indonesian,Chinese, Indian and orang asli (indig-

enous people) traditional medicines.2

The treatment of ailments uses a holis-tic approach, involving physical, spiri-tual, mental, emotional and behav-ioural factors. Often the diagnosis of aparticular disease is made based onan examination of physical conditionsand a determination of spiritual influ-ences such as "bad spirits" and ghosts.

In Malay traditional medicine, thephysical characteristics of a person arebelieved to be constituted of four ele-ments - suprawi (fire), suddawi (earth),dammawi (wind) and balpawi (water)(Figure 1).2, 3 These elements, humoursand descriptions of ailments are simi-lar to those described by the Greekmodel of elements and humours.

Besides chants (jampi), prayers(doa), massage, abstinence (pantang)and other practices, the Malay tradi-tional medicine also utilizes variousnatural resources from plants, animals,microorganisms and minerals for thepurpose of treating and preventing ill-nesses, and for rehabilitation andhealth promotion. Medications contain-ing single or compound medicinalplants may be dispensed in manyforms, such as powders, capsules,pills, makjun, medicated oils, simpledistillates, decoctions, infusions, pasteand poultices.

Scientific researchDocumentation of Malay TM practicesis rather scarce. Most practices rely on

old references, such as MujarabatMelayu, Tajul Muluk, Tajus as Salatinand Surat Tib Ubat. The earliest scriptson the ethno-botanical uses of Malay-sian plants dated back to the time ofBritish colonialism. Some of these werepublications4, 5, 6, 7, 1, 8 providing monu-mental references for researchers onthe utilization of medicinal plants inMalay traditional medicine.

Laboratory-based scientific re-search of Malaysian medicinal plantscommenced with phytochemicalscreening.9, 10, 11, 12 This was followedby the isolation and structural elucida-tion of pure compounds work in the six-ties.13 Since then research has greatlyexpanded on various medicinal plants,employing diverse research method-ologies, by several groups of research-ers, either locally or internationally.14

Due to a global awareness of theimportance of medicinal plants, re-search and development (R&D) onMalaysian herbals has become ofprime interest in most universities andresearch institutions. The Malaysiangovernment has given substantial sup-port and, since 1985, specific researchfunding had been allocated through itsIntensified Research in Priority Areas(IRPA) programme. Current R&D onMalay traditional medicine is concen-trated on ailment-based medicinalplants, using techniques such as bio-assay-guided isolation, determinationof biological, pharmacological and tox-icological effects, and herbal productdevelopment; and clinical trials.

Registration and qualitycontrol of TM productsWHO defines herbal medicines as “fin-ished, labelled medicinal products thatcontain as active ingredients aerial orunderground parts of plants, or otherplant material, or combinations there-of, whether in the crude state or as plantpreparations. Plant material includesjuices, gums, fatty oils, essential oils,and any other substances of this na-ture. Herbal medicines may containexcipients in addition to the active in-gredients. Medicines containing plantmaterial combined with chemicallydefined substances, including chemi-cally defined, isolated constituents ofplants, are not considered to be herbal

Figure 1: Principles of the Malay traditional medicine based on the Greekmodel of elements and humours

Balpawi(Water)

Suddawi(Earth)

(Air)Dammawi

(Fire)Suprawi

Fluid: PhlegmPhysical character:Fat, sleeps too much,dull and slow,stagnant

Fluid: BloodPhysical character:Thin, ruddy complex-ioned, feverish

Fluid: Yellow bilePhysical character:Speedy and hurriedperson, tranquil,feverish, lack of sleep

Fluid: Black bilePhysical character:Thin, hard-working,lack of sleep

Damp Dry

Cold

Hot



medicines. Exceptionally, in somecountries, herbal medicines may alsocontain, by tradition, natural organic orinorganic active ingredients which arenot of plant origin” (WHO, 1996a).

In the wake of increasing availabil-ity of herbal products and their usageby consumers, the Malaysian govern-ment imposed the Control of Drugs andCosmetics Regulation 1984 in the year1992, whereby all herbal products in-tended to be produced, imported and

sold for human consumption must beregistered with the Malaysian Ministryof Health in order to ensure and con-trol the quality, safety and efficacy ofthe herbal products.15 This step markedthe beginning of a systematic regula-tory control over herbal products pre-pared and sold in pharmaceutical dos-age forms, such as capsules, tablets,pills, liquid preparations, creams, lo-tions, suppositories, patches and oth-ers. Currently every registered tradition-

al medicinal product bears the regis-tration number on its label or package,starting with PBKD or MAL and endingwith T which denotes it is a traditionalmedicine product.

All manufacturers, importers, sup-pliers and wholesalers are also re-quired to be licensed by the Drug Con-trol Authority (DCA) of the MalaysianMinistry of Health. By the end of 2003,a total of 138 manufacturers and 121importers of traditional medicines had

Table 1: Some Malaysian plants yielding clinically useful drugsa

Species (Family)

Ananas comosus (L.) Merr.(Bromeliaceae)Andrographis paniculata Nees(Acanthaceae)Ardisia japonica Bl. (Myrsinaceae)Areca catechu L. (Palmae)

Azadirachta indica Juss.(Meliaceae)Carica papaya L. (Caricaceae)

Cassia app. (Leguminosae)Catharanthus roseus (L.) G. Don(Apocynaceae)

Centella asiatica (L.) Urban(Umbelliferae)Cinchona ledgeriana Moens exTrimen (Rubiaceae)Curcuma longa L. (Zingiberaceae)Datura metel L. (Solanaceae)

Dioscorea spp. (Dioscoreaceae)Glycyrrhiza glabra L.(Leguminosae)

Gossypium spp. (Malvaceae)Mentha spp. (Juncaceae)Nicotiana tabacum L. (Solanaceae)Quisqualis indica L.(Combretaceae)Rauwolfia serpentina (L.) Benth. ExKurz (Apocynaceae)

Ricinus communis L.(Euphorbiaceae)Strophantus pratus Baill.(Apocynaceae)

Strychnos nux-vomica L.(Loganiaceae)

Local Malayname

Nenas

Pokok cerita,hempedu bumi-Pokok pinang

Pokok mambu

Betik

-Kemunting cina

Pegaga

Kuinin

KunyitKecubung

GadungKayu manis cina

Pokok kapasPudinaTembakauAkar dani, akarpontianak-

Jarak

-

-

Drug

Bromelain

Andrographolide,neoandrographolideBergeninArecoline

Azadirachtin

Chymopapain

AnthraquinonesVinblastine, vincristine

Asiaticoside

Quinidine Quinine

CurcuminScopolamine

DiosgeninGlycyrrhizin

GossypolMentholNicotineQuisqualic acid

AjmalicineRescinnamine

Castor oil

Ouabain

Strychnine

Action/Clinical use

Anti-inflammatory,proteolytic agentBacillary dysentery

Anti-tussiveAnthelmintic

Insecticide(on non-food plants)Proteolytic, mucolytic

LaxativeAnti-tumour

Vulnerary

Anti-arrythmic, Anti-malarial, anti-pyreticCholereticSedative

ContraceptiveAnti-inflammatory,sweetener

Male contraceptiveRubefacientInsecticideAnthelmintic

Circulatory disorders,Anti-hypertensive,tranquillizerLaxative

Cardiotonic

CNS stimulant

a Based on data from Farnsworth & Soejarto (1992)36 and Burkill (1935)1



registered with the DCA. Manufactur-ers must be in full compliance with theCode of Good Manufacturing Practice,which is currently based on the WHOCode. Every product submitted for reg-istration is subject to laboratory analy-sis of physical, chemical and biologi-cal screening and testing. By law, onlyregistered herbal products are allowedto enter the Malaysian market andthese are also subject to regular andrandom post-marketing surveillanceand testing. However, the present ana-lytical procedures are rather restrictedand minimal, focusing only on severaltests for quality and safety:

Dosage performance: (i) uniformityof weight and (ii) disintegration test(for tablets, pills and capsules); andSafety assessment: tests for (i)heavy metals (arsenic, mercury,lead and cadmium), (ii) aerobicmicrobial content (gram positiveand gram negative bacteria, enter-obacteria, Escherichia coli,Pseudomonas aeruginosa, Sta-phylococcus aureus, Salmonellaand fungi) and (iii) scheduled poi-sons, such as agents for sexualdysfunction (sildenafil and talada-fil), slimming agents (sibutramine,fenfluramine and phentramine),antihistamine/antitussive (chlor-pheniramine, promethazine, etc),whitening agent (hydroquinoneand tretinoin) and steroids (dexam-ethasone, betamethasone, etc).

Due to limited information on pharma-cognostical data, biological activity,active ingredient(s), marker com-pounds and toxicity effects of manyMalaysian medicinal plants utilized invarious herbal products, the regulato-ry body is unable to screen for the iden-tity of ingredients as indicated on theproduct label, to determine the contentof potentially toxic substances and toassay the content of activeingredient(s) or marker compoundswhich are responsible for the specifiedactivity. Thus Ibrahim16 suggested thatmore stringent quality control proce-dures be implemented in order to curbunscrupulous vendors from marketingunsubstantiated or falsely claimedquality, safety and effectiveness inherbal products.

In Malaysia, herbal medicines arealso subject to other related regulatory

acts, such as the Medicines Act (Ad-vertisement & Sales) 1956 (Revised1983); the Poisons Act 1952 (Revised1989); the Drug Sales Act 1952 (Re-vised 1989); and the Wild Species Act1972. The DCA of Malaysia prohibitsall TM products from making any ther-apeutic claims of the cure, treatment,and prevention of certain diseases, 20of which are listed in Table 2.

However, some unethical tradershave used other terminologies or word-ings bearing similar indications, orhave distributed pamphlets stating theprohibited indications in order to pro-mote sales. On the other hand, func-tional claims, such as increasedstrength and vitality, are permitted. Ther-apeutic claims may be allowed forproperly standardized herbal productswith proven safety and efficacy, sup-ported by sound clinical data.

Herbal monographsHerbal monographs in national phar-macopoeias and other authoritativedocuments play an important role inthe authentication of herbal materials.

A monograph in this context is awritten specification that describes theprincipal features of a botanical drugand provides information and ways inwhich these features can be deter-mined that allows for its proper identifi-cation and quality standardization for“fitness of use”.

A pharmacopoeia, on the otherhand, consists of a collection of sever-al monographs. Such standard speci-fications are actually the key docu-ments in a quality assurance processfor the production of well-defined qual-ity, safety and efficacy of herbal drugsand preparations.

In many parts of the world, herbaldrugs (herbal raw materials) are re-quired to be authenticated to the rele-vant monograph in national pharma-copoeias such as British Pharmaco-poeia (BP), European Pharmacopoe-ia (EP) (BP-EP has 184 herbal drugsand preparations), the United StatesPharmacopoeia and National Formu-lary (USP-NF) (28 herbal drugs), thePharmacopoeia of the People’s Re-public of China (992 materia medicaand medicines), the Ayurvedic Phar-macopoeia of India (API) (362 herbaldrugs and preparations) and others, if

such monographs exist. Examples ofthe monographs included in the BP-EP are Alexandrian senna (Cassiasenna), aloe (Aloe spp.), belladonna(Atropa belladonna), centella (Centel-la asiatica), cinnamon bark (Cinnamo-mum zeylanicum), feverfew (Tanace-tum parthenium), ginkgo (Gingko bilo-ba), ginger (Zingiber officinale), gin-seng (Panax ginseng), isphagula(Plantago ovata), Java tea (Orthosi-phon aristatus), Java tumeric (Curcu-ma domestica), lavender (Lavandulaangustifolia), roselle (Hibiscus sabdar-iffa), etc. Other official documents ofherbal pharmacopoeias are BritishHerbal Pharmacopoeia (233 medici-nal plants), The American Herbal Phar-macopoeia (19 medicinal plants),Complete German Commission EMonographs (107 medicinal plants),ESCOP Monographs (60 medicinalplants), and WHO Monographs of Se-lected Medicinal Plants (92 medicinalplants). These would include mono-graphs for Aetheroleum MelaleucaeAlternifoliae (Melaleuca alternifolia),Black Cohosh (Actaea racemosa),Dang Gui Root (Angelica sinensis),Herba Andrographidis (Andrographispaniculata), Herba Centellae (Centel-la asiatica), Echinaceae (Echinaceaspp), Reishi mushroom (Ganodermalucidum), Valerian Root (Valeriana of-ficinalis), etc.

In Malaysia a herbal drug that isthe raw material used for the manufac-turing of pharmaceuticals from a vege-table source and intended for thera-peutic purposes, is authenticated andtested to a relevant monograph avail-able from any official pharmacopoeiasor documents. However, to date, prep-aration and registration of herbal prod-ucts for supplementation purposes of-ten do not require rigorous physico-chemical tests for the raw materials.Standardization of a raw material wouldmean authenticating and controllingthe quality of the plant material usedfor product manufacturing; that is, itshould have an acceptable content ofbioactive components; and it should besafe from toxic impurities (e.g. adulter-ation of poisonous plant materials, de-teriorated toxic phytochemicals, heavymetals and microbial contamination).Passing such physicochemical, andsometimes biological tests, of a mono-



graph would be a guarantee that theraw material is of pharmacopoeialquality and thus qualifies to be usedfor the production of a standardizedherbal product with consistent efficacyand safety.

Although monographs of com-monly used medicinal plants are al-ready available internationally, a mono-graph of a Malaysian medicinal planthas to be developed in order to suit lo-cal species, and geographical and en-vironmental conditions. That is alsowhy many countries develop their ownherbal pharmacopoeias; like the Jap-anese Standards for Herbal Medicines(248 medicinal plants), the Indian Herb-al Pharmacopoeia (52 medicinalplants), Materia Medika Indonesia, ThePhilippine National Formulary, Medic-inal Plants of Thailand and the Stan-dard of Asean Herbal Medicine.

Thus, the Scientific Committee ofMalaysian Herbal Monographs (SCM-HM) believes that the work on devel-oping monographs for Malaysian me-

dicinal plants is relevant in order to pro-vide a quality standard for manufactur-ing of local herbals, as well as to be inline with the neighbouring countries interms of controlling quality of herbalproducts.

The first volume of the MalaysianHerbal Monograph (MHM)17 was pub-lished in 1999, containing 20 mono-graphs of selected Malaysian medici-nal plants. Work is under way to pub-lish subsequent volumes of the MHM,with 20 Malaysian medicinal plants pervolume. A summary of the standardprotocol for the development of MHMis shown in Figure 2, involving multi-disciplinary scientists from various uni-versities and research institutions. Themonographs can then be utilized bythe manufacturers of Malaysian herb-al products and regulatory authoritiesas the principal quality control docu-ments. It is hoped that the governmentand herbal industries continue to sup-port the monograph research to achieveholistic benefits.

PhytopharmaceuticaltechnologyIn most TM practices, a patient is pre-scribed with a tailor-made remedy bya qualified and properly trained tradi-tional practitioner. The remedies aremostly prepared in the form of liquid(e.g. juice, decoction, infusion, tincture,etc.), solid (e.g. dry powder, dry exu-date), paste and oil. Treatment is oftenlimited to the period when the personis having the ailment. Currently manytraditionally prepared remedies havebeen transformed into modern phar-maceutical dosage forms for productreputation, convenience of the con-sumers and potential sales.

Ironically, these herbal medicineshave been considered as generalhealth supplements that consumerstake every day for an unlimited period.But unregulated or inappropriate useof herbal medicines can have nega-tive or dangerous effects. For example,the traditional Chinese medicine ephe-

Figure 2: Flow chart of research methodology performed for every volume of Malaysian Herbal Monograph (MHM)(Each contributor is responsible for generating the quality control data of the selected medicinal plant; the datais then verified by the Traditional Medicine Laboratory of National Pharmaceutical Control Bureau (NPCB) ofthe Ministry of Health, Malaysia.)

Drawing of fresh plants(Artistic drawing of whole plant)

Macroscopy(Morphological description of plant part)

Macroscopy(Cross sectional study of plant part)

CharactersDetermination of physical char-acters of powdered specimen• Colour• Odour• Taste

MicroscopyMicroscopical description ofpowdered specimen• Identification• Photographic capture• Artistic drawing

Colour testsDetermination of colourdue to chemical reaction• Conc. HCl & H2SO4• 5% NaOH, 5% KOH,

25% NH4OH, FeCl3

Ash contentLimit of silicaceousimpurities & earthy materials• Total ash• Acid-insoluble ash• Water-soluble ash

TLCDetermination of fingerprintprofiles of plant extracts• Use HPTLC• Choose best mobile phase• Various detection methods

Other techniques• Essential oil content• HPLC fingerprint• GC fingerprint• UV fingerprint• FTIR fingerprint

Extractive valuesDetermination of extractablematter• EtOH-soluble (hot & cold)• H2O-soluble (hot & cold)• Other suitable solvents

Voucher specimen(Deposition at FRIM)

Processing of medicinal plants(Garbling, drying & grinding; 5 kg dry wt each specimen)

Collection of medicinal plants(3 locations per species; 10-20 kg fresh wt each specimen)

Selection of medicinal plants(20 species based on popularity of use of registered products)

Verification of contributor's data(Repeat experiments by the Traditional Medicine Lab, NPCB)

Presentation of final data(Review of results by the Scientific Committee of MHM)

Preparation of MHM(Compile, edit & proof read by the Scientific Committee of MHM)

Publication of MHM

Preparation of monograph(By the respective contributor)

Expe

rimen

tal s

tudy

by

cont

ribut

or



dra, for treating respiratory congestion,was used in the USA as a dietary aid,whose over-dosage led to deaths, heartattacks and strokes (WHO, 2003a).

One must bear in mind that plantscontain numerous chemicals as a re-sult of their natural metabolic activities.These chemicals may be essential forplant growth or as by-products of itsmetabolism; they may also be poten-tially useful as food or medicine, orpotentially harmful or poisonous forpeople and animals. For example,starch functions as an energy store forsome plants, has nutritional value forhumans and is utilized as a pharma-ceutical excipient. Morphine is ob-tained from the opium poppy (Papaversomniferum) as a powerful analgesic,anti-tussive and anti-diarrhoeal, butcan also have toxic effects, includingimpairment of mental performance,euphoria, drowsiness, lethargy, blurredvision and constipation. In fact, someplants can cause allergic reactions,such as irritation to the respiratory sys-tem, skin, eyes and oral cavity. Thus,all medicinal plant materials, utilizedeither internally or externally, have tobe considered as medicines. Strict con-trol and careful administration of herb-al products are vital to provide consum-ers with standardized quality, safetyand efficacy.

Standardization procedures forherbal medicines should not be limit-ed to finished products only. Theyshould take a holistic approach, cov-ering at least the following areas:

Selection of a “gold” breed of me-dicinal plant;Cultivation techniques and essen-tial growth requirements (e.g. geo-graphical and climatic conditions);Harvesting period (e.g. age of plant),time (e.g. day or night, season, etc)and methods (e.g. manual or me-chanical);Treatment processes (e.g. garbling,drying, grinding, extraction, etc);Quality control of plant materials(e.g. macroscopy and microscopy;identification tests using chromato-graphic and spectroscopic analy-sis; gravimetric analysis of extract-able matter; limit tests for moisture,ash, heavy metals, microbial andpesticide contamination; assay ofbioactive or chemical markers);Manufacturing of herbal products(e.g. herbal tea in sachets, pharma-ceutical dosage forms, etc.);Packaging materials (e.g. plastic orglass bottles, blister pack, etc.);Sterilization techniques;Storage conditions (e.g. tempera-ture, shelf life); andTransportation methods.

These activities would involve multi-disciplinary experts, such as botanists,farmers, phytochemists, biochemists,pharmacologists, pharmaceutical an-alysts, biotechnologists, and chemicalengineers.

Standardization of herbal medi-cines is of utmost importance in orderto ensure consistent batch-to-batchquality, safety and efficacy. The effica-

cy and safety aspects of a medicinalplant are due to its biological activity,which, in turn, is based mainly on theamount or concentration of the chemi-cals present in raw or processed (e.g.extract, distillate, oil, juice) forms. Be-cause these chemicals are metabolicproducts of plants, their formation andstability are often affected by variousinternal and external factors - genes,geography (e.g. altitude, latitude andsoil type), climate (e.g. sunlight, humid-ity and rainfall) and deterioration (fun-gal and bacterial attack, temperature,hydrolysis by moisture, photodecom-position by direct exposure to sunlight,oxidation by oxygen, etc).

The WHO has published severalimportant guidelines pertaining to var-ious aspects of herbal medicines, suchas the regulation and practice of herb-al medicines (WHO/TRM, 1998; WHO/WPRO, 1998), assessment of safetyand efficacy (WHO/WPRO, 1993;WHO, 1996a; WHO MD, 2000; WHO,2004), quality control of medicinal plantmaterials (WHO, 1998a), agriculturaland collection practices (WHO, 2003b),manufacturing processes (WHO,1996b), evaluation of medicinal dos-age forms (WHO, 1998b) and conser-vation (WHO, 1993). These cover thewhole spectrum of standardization pro-cedures of herbal medicines. An out-line of essential standardization pro-cesses is shown in Figure 3.

Proper quality control can ensureconsumer and operator safety, consis-tent formulation and therapeutic doseof medicines, reliable clinical effect,brand reputation and cost effective-ness; besides being a requirement ofquality assurance in Good Manufac-turing Practice (GMP).

Case study: Labisia pumilaLabisia pumila (Bl.) F.-Vill (syn.: Labi-sia pothoina Lindl., family: Myrsinace-ae), popularly known as Kacip Fatimah,has been used by many generationsof Malay women to induce and facili-tate childbirth, and as a post-partummedicine,18 as well as for flatulence,dysentery, dysmenorrhoea and gonor-rhoea, ‘sickness in the bones’1 andhaemorrhoids.19

There are three varieties of L. pum-ila, i.e. L. pumila var. pumila, L. pumila var.

1. Diseases or defects of thekidney

2. Diseases or defects of theheart

3. Diabetes4. Epilepsy5. Paralysis

6. Tuberculosis7. Asthma8. Leprosy

9. Cancer10. Deafness11. Drug addiction

Table 2: List of therapeutic claims for TM products that are prohibited bythe Drug Control Agency of Malaysia

12. Hernia or rupture

13. Diseases of the eye14. Hypertension15. Mental disorder

16. Infertility17. Frigidity18. Impairment of the sexual

function or impotency19. Venereal disease20. Nervous debility, or other

complaint or infirmity, arisingfrom or relating to sexualintercourse



alata (Scheff.) Mez. and L. pumila var.lanceolata (Scheff.) Mez.20 Preliminaryscreening of the medicinal plants sug-gests that the var. alata is more com-monly used in traditional medicinepreparations.

Previous scientific studies re-vealed that extracts of L. pumila hadvarious activities such as antibacterialeffect21, oestrogenicity in vitro,22, 23 PAFreceptor binding inhibition in vitro24 andanti-oedema in vivo.25 The plant wasalso found to contain benzoquinoidderivative (Houghton & Jamal, 1999),26

alkenyl resorcinols27 and triterpenoidcompound (unpublished data).

Based on various sources of eth-nobotanical information,1, 28, 21, 29 it canbe assumed that L. pumila has tradi-tionally been prepared in a form ofwater decoction of either the leaf partor the root part or the whole plant. Thepreparation may also contain othermedicinal plants.

Recently a supplement drink con-taining L. pumila var. alata was intro-duced into the Malaysian market andis becoming popular. Thus this labo-ratory-based study is aimed to formu-late the water extract of L. pumila var.alata into a solid pharmaceutical dos-age form of tablets for the conve-nience of administration by consum-ers. Various research methodologiesand data, such as quality control ofraw materials based on pharmacog-nostical evaluation, extraction tech-niques and parameters, and tablet for-mulations, have been obtained for thepurpose of proper standardization tohelp ensure the quality, safety and ef-ficacy of herbal products containing L.pumila var. alata.

Quality controlof raw materialsThe flow of quality control processesof L. pumila var. alata is summarizedin Figure 4. Based on the informationobtained from the study, L. pumila var.alata can be physically differentiatedfrom other varieties based on the broad-ly-winged character of the leaf petiole(Figure 5). A powder of the dried L.pumila var. alata would contain char-acteristic multicellular peltate trichomeand numerous calcium oxalate clystercrystals (Figure 6) when analyzed mi-croscopically.

The leaves and roots of L. pumilavar. alata were subjected to gravimet-ric analysis (Table 3); such as extract-able matter, including cold water-solu-ble extractives using maceration andhot water-soluble extractives using re-flux extraction; moisture content by theloss-on-drying method; and heavy met-als (arsenic, lead, mercury and cadmi-um) using the atomic absorption spec-troscopic method. In extractive analy-ses, it is revealed that substances are

more easily extracted by soaking in hotwater than through using the macera-tion technique, suggesting that heatencourages extraction of the water-sol-uble matter from L. pumila var. alata.This scientifically substantiates its tra-ditional method of preparation by de-coction. The plant was found to have aslightly high moisture content that couldbe associated with its natural growthhabitat of shady and humid areas.

Thus, it is suggested that the rawplant materials should be thoroughly

Figure 3: Flow of research methodology for the standardization of herbalmedicinal products

Figure 4: Flow of quality control processes of raw materials of Labisiapumila var. alata

Samples from supplier(Dried leaves)

Physicalinspection

Sampling for analysisand grinding

Laboratory analysis

Gravimetry Limit tests Chemical screening Bioassay

Oestrogenicity

Antioxidant

Antimicrobial

GC-ZnoseHPLC

FTIRUV

HPTLC

Microbials

Heavy metalsExtractives

Water content

Ash content

Preparation of test protocols and materials

Crude Extracts

QC laboratory analysis

Standardized materials

Toxicological studies Manufacturing process

Pharmacological studies Pharmacokinetic studies

Clinical studies



Figure 5: (A) Voucher specimen of dried whole plant of Labisia pumila var. alata. The variety has broadly-wingedleaf petiole. (B) Young plants of Labisia pumila var. alata cultivated away from its natural forest habitat.The plants usually take at least six months to mature.

Figure 6: Characteristic microscopical features of dried and powdered whole plant of Labisia pumila var. alata,observed under an optical microscope of x400 magnification factor, using liquid paraffin as a mountingagent. (A) Glandular multicellular peltate trichome. (B) Calcium oxalate cluster crystals (cc)

dried prior to further processing, in or-der to protect it from deterioration bymould or bacterial growth, or by possi-ble enzymatic or chemical hydrolysisof its active ingredients. The low levelof heavy metals in L. pumila var. alataindicates that the plant may not be apotential metal accumulator, therefore,it may not potentially pose the risk ofheavy metal toxicity in humans.

Fingerprinting of rawmaterialsThis study aims to establish qualitativechemical methods for the identificationand authentication of its raw materials,so as to complement the pharmacog-nostical data, for the purpose of qualitycontrol. Chromatographic and spectro-scopic analyses were performed onplant materials of L. pumila var. alata

collected from ten different locations ofWest Malaysian forests. Thin layer chro-matographic (TLC) profiles of the eth-anolic (96 per cent) extracts were ob-tained using high-performance TLC(HPTLC) plates of silica gel F254 withCHCl3-MeOH (10:1) as the mobilephase. Slightly different TLC band pro-files were seen between the root andthe leaf extracts (Figure 7).

A B

A B

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Ultraviolet (UV) spectrophotometricspectra of the ethanolic (70 per cent) rootand leaf extracts yielded absorptionmaxima of various intensities at maxi-mum wavelength range of 278-280 nmand 280-282 nm, respectively (Figure 8).In addition, infrared (IR) spectrophoto-metric spectra of the raw powder of theroots and leaves (as potassium bromidediscs) showed almost similar absorptionband profiles; however, the leaf sampleshad distinct bands in the fingerprint re-gion of 750-700 cm1 (Figure 9).

TLC is most often used as a pre-liminary screening method to authen-ticate the identity of the plant materialsbased on their characteristic profiles("fingerprints"). Other techniques suchas high-performance liquid chromatog-raphy (HPLC), gas chromatography(GC), UV and IR have been used astools to control the quality of herbalmaterials and products, owing to thefact that these techniques are accurate,sensitive and reproducible, as well assimple to operate and reasonablycheap. With recent advancements,more objective qualitative measure-ments can be made using chemomet-rical evaluation methods.30, 31

Quantitative analysisA preliminary phytochemical study suc-cessfully isolated a major componentof benzoquinoid derivative which waschosen as a marker. The quantitativeanalysis was performed on the abovesamples, using HPTLC-densitometricanalysis in CHCl3-EtOAc (3:2). The datarevealed that, in general, the root ex-tracts (7.19-38.92 %w/w) had a highercontent of marker component than theleaf extracts (0.00-10.93 %w/w).

The technique used in this study isapplicable and reasonable for the quan-tification (assay) of marker compoundsin L. pumila var. alata, especially whenmost of the other chemical componentsare unknown. However, other analyti-cal techniques such as HPLC may be amore useful and reliable monographicmethod. Work is underway to establishthe proper qualitative and quantitativeevaluation using HPLC.

Extraction methodsfor product developmentThe best method and parameters ofextraction of the water extract of L. pum-

ila var. alata was determined.32 Labo-ratory-based methods of maceration,decoction, reflux and Soxhlet wereused, whereas the parameters studiedwere temperature and duration of ex-traction. In general, the percentage ofyield is higher for the root extract thanthe leaves; and that obtained from heat-ing is higher than that obtained at roomtemperature. Based on the results, theideal water extraction method and pa-rameters (temperature and duration)for L. pumila var. alata are found to bethe following: maceration (25oC, e” 6h), decoction (60oC, d” 10 mins) andreflux (100oC, d” 4 h). Soxhlet wasfound to be the most ineffective meth-od for laboratory extraction. Thus it canbe suggested that large-scale extrac-tion may be done under low tempera-tures at a reduced pressure, in order to

obtain optimum yield - for example,using the supercritical fluid extraction(SFE) technique.

Tablet formulationSeveral formulations containing thewater-soluble freeze-dried or spray-dried extract of L. pumila var. alata anddifferent excipients were prepared byeither direct compression or wet gran-ulation tabletting methods. Accordingto the British Pharmacopoeial specifi-cations, the tablet formulation is con-sidered acceptable when it passes theperformance tests of friability (maxi-mum loss of 1 per cent), disintegrationtime (not less than 15 minutes) and dis-solution rate (not less than 70 per centin 45 minutes).

Using the direct compressionmethod, a formulation containing the

Labisia pumila var. alata % w/wGravimetric method Leaves Roots

Cold water-soluble extractive e” 9% w/w e” 12% w/w

Hot water-soluble extractive e”13% w/w e” 17% w/w

Moisture content (by loss on drying) d” 11% w/w d” 11% w/w

Total ash d” 11% w/w d” 11% w/w

Acid-insoluble ash d” 1% w/w d” 1% w/w

Water-soluble ash d” 7% w/w d” 3% w/w

Arsenic content < 5 ppm < 5 ppm

Lead content < 10 ppm < 10 ppm

Mercury content < 0.5 ppm < 0.5 ppm

Cadmium content < 0.3 ppm < 0.3 ppm

Table 3: Limits of extractable matter (extractive), moisture content andash, and content of heavy metals based on the data obtained fromgravimetric analysis of the leaves and roots of Labisia pumila var.alata

Formulations of Labisiapumila var. alata water extract

Direct Direct DirectTest methods compression compression compression

of freeze-dried spray-dried of freeze-driedextract extract extract

Friability (% w/w loss) 0.92 0.75 0.67

Disintegration time (mins) 7.27 14.06 13.22

Dissolution rate(mins for 70% release) 5 > 45 27

Table 4: Data of friability, disintegration time and dissolution rate of for-mulations containing water extract of Labisia pumila var. alata



freeze-dried water extract of L. pumilavar. alata, microcrystalline cellulose,calcium lactate pentahydrous, Clear-am CH20 (modified corn starch) andmagnesium stearate were found to beacceptable (Table 4).33 However, in thisstudy, the utilization of corn starch,stearic acid and more than 25 per centmicrocrystalline cellulose was found todecrease the dissolution rate of theextract. The spray-dried tablets prepared

by the direct compression method failedthe dissolution test, and the study sug-gested that the use of microcrystallinecellulose and Clearam CH20 were in-compatible with the spray-dried ex-tract.34 In the wet granulation study, aformulation containing L. pumila var. al-ata freeze-dried water extract, polyvi-nylpyrrolidone, potato starch, magne-sium stearate and lactose producedacceptable pharmaceutical perfor-

mance.35 However, the disintegrationtime and dissolution rate are greatly in-creased, as compared to the freeze-dried water extract tablets prepared us-ing the direct compression technique.

From the study it can be concludedthat the excipients used in the formula-tion and tabletting method can affect theperformance of tablet preparation. Atpresent, herbal medicinal products intablet dosage forms, especially thosecontaining freeze or spray dried extracts,are very limited in Malaysia. This couldbe due to the tedious R&D taken to ac-quire the optimum formulation. Howev-er, in the long run herbal tablet prepara-tions are more cost effective than thoseprepared in hard gelatine capsules.

Opportunities for businessThe increasing demand for traditionalmedicinal products provides vast op-portunities for SMEs. In Malaysia, anoverwhelming awareness and interestby the general public have encouragedthe herbal products industry. A furtherboost has come from governmentalpolicies giving emphasis and prioritiesto sectors such as scientific R&D,agroindustry, manufacturing industryand trading activities. Many scientistsfrom public and private universities andcolleges, as well as research institu-tions, have great interest and are com-mitted to natural or herbal products.However, not many of their researchfindings are being exploited. HereSMEs can tag along with particulargroups of experts to commercializetheir research concepts, as well as torectify problems of producing “ques-tionable” herbal products that lack sci-entific data and evidences.

Other systematic approaches aresuggested here:

For a new herbal product, SMEscan first identify those types of herb-als or species of medicinal plantswith potential market value, basedon either trend or popularity of use;or those that have been thorough-ly-studied; or those with ethnobo-tanical uses (though this is current-ly not a popular basis).Retail or multi-level marketing busi-nesses can be set up to providemeans of selling TM, food and nu-tritional supplements directly toconsumers. Properly registered and

Figure 7: (A) Thin layer chromatographic (TLC) chromatogramme of theethanolic (96%) extracts of Labisia pumila var. alata roots (R)and leaves (L) collected from various sites in Malaysian forests.The chromatogramme was obtained using high-performance TLC(HPTLC) plates of silica gel F254 with CHCl3-MeOH (10:1) as themobile phase. Observation was made under daylight after treat-ment with Anisaldehyde-sulphuric acid spray reagent. (B) Two-dimensional TLC chromatogramme of (A), showing the varioustypes of chemicals and content as indicated by the peaks.

(A)

(B)

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permanent premise sites are en-couraged so as to portray formal-ized business and prestige. In fact,most educated and professionalconsumers prefer to purchaseproducts from such premises, be-cause it would be easier for themto refer back in case of any prob-lems. It is also highly recommend-ed that only registered and non-expired traditional medicinal prod-ucts are placed on the shelves, andthat staff are properly trained andwell-informed of the products,mainly for company reputation.Another most popular method ofbusiness is in trading activities (asimporters, exporters or wholesal-ers). The companies either importor export and distribute raw materi-als to manufacturing industries, orrepackage herbal ingredients intobrand name products. It is highlyrecommended that these compa-nies closely monitor the quality ofthe plant materials or ingredients,by either having their own qualitycontrol laboratories or sending toprivate laboratories for analysis, inorder to reduce the risks of sellingproblematic products.SMEs can also manufacture theirown herbal products. However, thiswould require extremely high cap-ital for construction and mainte-nance of a GMP and Good Labora-tory Practice (GLP) compliance pre-mises and facilities, as well as prop-er human resources. Manufactur-ers must also consider long-terminvestments in scientific R&D toproduce products of high quality,safe and efficacious, so that the out-put outweighs the expenses. SMEsin Malaysia can refer to organiza-tions such as Malaysian HerbalCorporation (MHC) and MalaysianOrganization of Pharmaceutical In-dustries (MOPI).On the other hand, SMEs can ven-ture into cultivation and processingindustries as suppliers of herbalraw materials. Particularly in Malay-sia, this type of business is not well-developed yet, but SMEs shouldtake up the opportunity, especiallynow that the government has putits focus on agroindustry. SMEswould require knowledge on GoodAgricultural and Collection Practice

(GACP) and Good Harvesting Prac-tice (GHP) to ensure sustainablesupplies of herbal materials of con-sistent quality. They can also seekhelp from specific research institu-tions. In Malaysia, these would bethe Forest Research Institute of Ma-laysia (FRIM) and the MalaysianAgricultural Research and Develop-ment Institute (MARDI).

ConclusionIn promoting the proper use of herbalmedicinal products, a comprehensive

programme of R&D, cultivation, pro-duction, trade and appropriate use inthe community and healthcare sectorsmust be encouraged and supported.Thus a joint, coordinated and holisticeffort among scientists, farmers, man-ufacturers, traders, health care profes-sionals and regulatory authorities isrequired to drive the industry to com-ply with consumer expectations of qual-ity, safety and efficacy in herbal prod-ucts. Ethics should underlie personaland business interests, so as not tojeopardize the consumers’ health.

Figure 8: Ultraviolet (UV) spectrophotometric spectra of the ethanolic(70%) extracts of Labisia pumila var. alata roots (A) and leaves(B) collected from various sites of the Malaysian forests.

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AcknowledgementThe author would like to express hersincere thanks and appreciation to Pro-fessor Dr. Zhari Ismail (School of Phar-maceutical Sciences, University of Sci-ence Malaysia), and Professor Dr. Ibra-him Jantan and Dr. Mohd. Cairul IqbalMohd. Amin (Department of Pharmacy,Faculty of Allied Health Sciences, Na-tional University of Malaysia) for theirscientific contribution and support. Theresearch on Labisia pumila var. alatawas funded by the Malaysian Govern-ment through the IRPA programme (06-05-01-002 BTK/ER/013).

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Figure 9: Fourier-transform infrared (FTIR) spectrophotometric spectra ofthe ethanolic (70%) extracts of Labisia pumila var. alata roots (A)and leaves (B) collected from various sites in Malaysian forests.

(A)

(B)

1.0000.950.900.850.80

0.750.700.650.600.550.50A0.450.400.35

0.300.250.200.150.100.05

0.0003999.0 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 398.5

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1.0000.950.900.850.80

0.750.700.650.600.550.50A0.450.400.35

0.300.250.200.150.100.05

0.0004000.0 3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 398.5

1/cm



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Malay traditional medicine