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j ournal of herbal med ic ine 4 ( 2 0 1 4 ) 5173

Available online at www.sciencedirect.com

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amu: Indonesian traditional herbal medicineowards rational phytopharmacological use

lfahmia, Herman J. Woerdenbagb, Oliver Kayserc,

School of Pharmacy, Institut Teknologi Bandung (ITB), Jl Ganesha 10, Bandung 40116, Indonesia and Departmentf Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1,713 AV Groningen, The NetherlandsTechnische Biochemie, Technische Universitt Dortmund, Emil-Figge-Strasse 66, 44227 Dortmund, Germany

r t i c l e i n f o

rticle history:

eceived 2 June 2012

eceived in revised form

October 2013

ccepted 7 January 2014

vailable online 26 January 2014

eywords:

amu

ndonesian medicinal plants

hytomedicine

harmacological activity

a b s t r a c t

Jamu is the Indonesian traditional herbal medicine that has been practised for many cen-

turies in the Indonesian community tomaintain good health and to treat diseases. Although

modern (conventional) medicine is becoming increasingly important in Indonesia, jamu is

still very popular in rural as well as in urban areas. Based on its traditional use jamu is

being developed into a rational form of therapy, by herbal practitioners and in the form of

phytopharmaceuticals. Jamu has acquired a potential benefit, both economically and clini-

cally. We surveyed the most frequently used plants in jamu that have also been investigated

regarding their constituents and pharmacological effects. The Indonesian government has

divided the preparation of medicinal plants into three categories, i.e. jamu, standardized

herbal medicines and fitofarmaka (phytomedicines). As the biological activity ascribed to

jamu is largely based on empirical data, more research is needed to scientifically prove

efficacy and to assure safety. In the further development of jamu, ethical issues such asintellectual property rights, benefit sharing, biodiversity and conservation need to be con-

sidered. This paper aims to review the current status of jamu and to give comprehensive

views that can be used in its future development for the further improvement of its utility

d ma

2014 Elsevier GmbH. All rights reserved.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52in curing illnesses an

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2. Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3. Indonesian medicinal plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.1. Biodiversity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.2. Recent research development and research communit3.3. Economical prospective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Corresponding author at: Technische Biochemie, Emil-Figge-Strasse 6ax: +49 231 7557 489.

E-mail address: [email protected] (O. Kayser).210-8033/$ see front matter 2014 Elsevier GmbH. All rights reservettp://dx.doi.org/10.1016/j.hermed.2014.01.002intaining good health.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

6, 44227 Dortmund, Germany. Tel.: +49 231 7557 487;

d.

dx.doi.org/10.1016/j.hermed.2014.01.002http://www.sciencedirect.com/science/journal/22108033http://www.elsevier.com/locate/hermedhttp://crossmark.crossref.org/dialog/?doi=10.1016/j.hermed.2014.01.002&domain=pdfmailto:[email protected]/10.1016/j.hermed.2014.01.002

52 j ournal of herbal med ic ine 4 ( 2 0 1 4 ) 5173

3.4. Ethical considerations in the development of medicinal plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534. Jamu as a way of traditional healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

4.1. Rational phytotherapy with jamu and phytomedicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564.2. Preparation of jamu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564.3. Legislative aspects of jamu and phytomedicines in Indonesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

5. Biological activity of the most common plants in jamu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615.1. Anticancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615.2. Antiviral. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635.3. Antimalarial and antiparasitic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635.4. Anti-inflammatory, antirheumatic, antipyretic and analgesic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645.5. Hepatoprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645.6. Antidiabetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645.7. Antimicrobial and antifungal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655.8. Gastroprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655.9. Cardioprotective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665.10. Antihypertensive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665.11. Anti-asthma, antitussive and anti-allergic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665.12. Immunostimulating. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675.13. Central nervous system (CNS) activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675.14. Others. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

6. Known risks and side effects of medicinal plants used in jamu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 677. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681. Introduction

Next to the Amazon rain forests, Indonesia has the secondbiggest biodiversity in the world expressed by a high numberof indigenous medicinal plants. Based on this rich source ofmedicinal plants, most of the Indonesian people especially inrural areas use traditional herbal medicines known as jamu totreat disease. Jamu is aword in Javanese tribal language,mean-ing the traditional medicine from plants. Minerals, animalsand parts thereof have also been used but are not the sub-ject of this review. Today, jamu has been adopted into BahasaIndonesia with the similar meaning (Riswan and Roemantyo,2002). Jamu gendong is a kind of traditional jamu sold without alabel and freshly prepared (not preserved) from plant materialin warung, the ubiquitous stalls along the streets in Indonesia(Limyati and Juniar, 1998; Suharmiati, 2003). Jamu gendong isinstantly served to whom orders this jamu requested prepara-tion. The sellers bring the jamu from door to door. The wordgendong itself means to carry something on the back of a body.The fresh jamu is put inside the bottles and stored in bam-boo or rattan baskets and they use a long wide shawl calledselendang for carrying the baskets on their back (Riswan andRoemantyo, 2002). Nowadays the production of jamu is alsobeing developed on an industrial scale. The Indonesian gov-ernment, industry and academia all recognize that to furtherthe development of jamu, extensive research is required toestablish the safety and efficacy of the many traditional jamupreparations.

This paper reviews the use of Indonesian medicinal plantsused in jamu medicine including its history, current status,

economic potential and scientific development plus possiblefuture developments.2. Methodology

Both online and offline literature searches were carried outto compile this review. PubMed (Medline), Highwire and ISIWeb of Science were used to retrieve any online publica-tions using the following search terms: Indonesia, medicinalplants, ethnopharmacology, jamu, phytomedicine, specificplant species, herbal medicines, natural product medicines,phytochemistry, pharmacognosy. Local library searches look-ing at the Medicinal Herbs Index in Indonesia (Anonymous, 1995)were also carried out by Indonesian researchers able to readold Java language in the cities of Bandung (the capital ofWest-Java province) and Yogyakarta (an old cultural city in centralJava). About 5000 species of medicinal plants were retrievedfrom the Medicinal Herbs Index in Indonesia and the plants thataremost frequently used as constituents of jamu are discussedin this paper.

3. Indonesian medicinal plants

3.1. Biodiversity

Biodiversity is defined as the variety of all life forms on earth,along with the interactions between them and their physi-cal environment. As an archipelagic state with thousands ofislands, Indonesia is endowed with a rich and unique biodi-versity. The area of Indonesian tropical forests covers about143 million hectares and is home to about 80% of the worlds

medicinal plants. It is estimated that the Indonesian tropicalforests contain 28,000 plant species. There are various reportsconcerning the inventory of higher plants in Indonesia. The

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ndonesian Country Study on Biodiversity (ICSBD 1993) esti-ates the number of flowering plants species in Indonesia toe between 25,000 and 30,000. Some 40 million Indonesiansave historically used the herbal medicines for protectionnd the treatment of diseases and the Indonesian communityakes use of around 6000 plant species. Data of the numberf medicinal plants also vary. PT Eisei (1995) published the Dic-ionary of Indonesian Medicinal Herbs containingmore than 2500lant species which principally can be developed for medici-al purposes, while Zuhud et al. (2001) identified 1845 speciesith medicinal potential in the forests of Indonesia. Theseumbers are potentially to be updated due to the continu-ng inventory and investigation of yet unidentified species.ccording to the National Agency of Drug and Food ControlNADFC/BPOM), 283 plant species have been officially regis-ered for their medicinal use; the larger remainder is usedraditionally.

To facilitate the activities on the conservation and sus-ainable use of biodiversity of Indonesian medicinal plantss medicines and functional foods, the Indonesian Govern-ent, through the National Development Planning Agency

BAPPENAS), has launched the Indonesian Biodiversity Strat-gy and Action Plan 20032020 (IBSAP). IBSAP is based onhe evaluation of the previous action plan from 1993 calledAPI (Biodiversity Action Plan for Indonesia), formulated inollaboration between the Indonesian Government (BAPPE-AS), the Ministry of Environment, research institutes andon-governmental stakeholders with the support of the inter-ational development institutions.

.2. Recent research development and researchommunities

valuation of jamu as a rational phytotherapy has to coverifferent areas of research including social, cultural, eco-omic, and ethical viewpoints. Preclinical pharmacologicaltudies have been carried out with extracts and isolatedompounds, and even a few clinical studies are available.owever, jamu is still largely not evidence-based from alinical perspective. The results from in vitro and in vivo pre-linical studies support the traditional use of many jamuroducts.Many institutions in Indonesia, especially governmen-

al institutions such as the Ministry of Health, Ministryf Forestry, Ministry of Environment, Ministry of Agricul-ure, the National Development Planning Agency (BAPPENAS),he National Agency of Drug and Food Control (NADFC orPOM) are engaged in research directed at the develop-ent of medicinal plants. The universities are also actively

nvolved in plant research through their related facultiesr departments from a variety of different areas such asedicine, pharmacy, chemistry, biology, agriculture, forestry,arine, environment and engineering. National research

nstitutions such as the Indonesian Institute of Sciencend the Herbarium Bogoriense, are involved in the devel-

pment of jamu as well as non-governmental institutionsuch as KEHATI (Indonesian Biodiversity Foundation), WALHI,KEPHI, and various industrial companies (Bermawie et al.,005).ine 4 ( 2 0 1 4 ) 5173 53

3.3. Economical prospective

Since the 1980s small jamu producers have grown sufficientlyto introduce larger scale and modern production methods(Beers, 2001). The jamu producing industry now has an annualgrowth of 2530%, according to BPOM. According to Pramono(2002) there are about 810 companies active in the productionof Indonesian traditional medicine of which 87 are classifiedas IOT (Industri Obat Tradisional, Traditional Medicine Industry)and 723 as IKOT (Industri Kecil Obat Tradisional, Small Industryof Traditional Medicine). In 2005, 872 companies in this fieldwere registered at NADFL. In addition, 462 companies fromforeign countries also play a role in the production of Indone-sian traditional medicine. About 20 national companies arethemajor players. Examples of jamu products from these com-panies are shown in Table 1. The industry revenue from jamuin 2000 was estimated to be 150 million USD. This amount ofrevenue can potentially be increased (Pramono, 2002). In theperiod between January and June 2005, the export ofmedicinalplants from Indonesia such asAmomum cardamomum, Burmani,Piper species and many others used to make jamu reached anamount of 126.8 million USD (Ministry of Industry, Republic ofIndonesia, 2005).

3.4. Ethical considerations in the development ofmedicinal plants

Intellectual property rights (IPR), indigenous knowledge, ben-efit sharing, efficacy and safety are issues that must beconsidered in the further development of Indonesian medic-inal plants. Jamu has been handed down from generation togeneration based on the traditional knowledge and experi-ence of the community.When newplant-derived therapeuticsbased on indigenous knowledge are being explored, it isimportant that the companies return benefits to the nativepopulation and the local governments from which theresearch material was obtained (King et al., 1996). Whenindividuals or institutions from biotechnologically developedcountries wish to obtain indigenous raw material from abiotechnologically less developed country, an agreement forthe procurement of such material may be negotiated. In arti-cle 19.2 of the Rio Convention (1992) there is an agreementin regard to the handling of biotechnology and distributionof its benefits. It is mentioned that each contracting partyshall take all practicable measures to promote and advancepriority access on a fair and equitable basis by contract-ing parties, especially developing countries, to the resultsand benefits arising from biotechnologies based upon geneticresources provided by those contracting parties. Such accessshall be on mutually agreed terms. Goodwill to maintainsuch a flow may be achieved through appropriate scientificand monetary compensation, both in real time and in long-term sharing of the benefits of discovery (Soedjarto, 1996).Over-harvesting may render medicinal plants into endan-gered species. Individuals or institutions exploring medicinalplant material also have responsibilities for their conserva-

tion. Most of the current knowledge that jamu can maintainhealth and/or cure certain diseases comes from the nativepeople who have experienced success in curing illness by tak-ing jamu It remains to be proven that jamu fulfils the generally


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Table 1 Examples of jamu products (and composition) from the major Indonesian jamu companies.

Industry name Jamu name Ingredients Indications/use

Sariayu Martha Tilaar Post Partum Herbs Calami rhizoma, Zingiberis purpurei rhizoma, Ligusticae acutilobumaeradix, Baeckeae folium, Curcumae domesticae rhizoma, Parkiaesemen, Isorae fructus, Sappan lignum, Curcumae rhizoma,Andrographidis herba, Caryophylli flos

Relieves abdominal pain after givingbirth, eases excrements and vaginalinflammations. Stimulates bloodcirculation and improves appetite anddigestion as well as strengthening andpromoting health generally

PT. Phapros Menstralax Ligustici rhizoma, Paeomiae alba radix, Polygalae tenuifolia radix,Rehmanniae preparata radix, Carthami tinctorius flos, Leonuriheterophyclus herba, Angelicae sinensis radix, Concha ostrea gigas,Albizziae julibrissin cortex, Moutan radicis cortex

Regulates endocrine gland secretion andmenstruation, promotes ovulation,reduces menstrual clots

PT. Sido Muncul Sakit kencing Orthosiphonis folium, Ligustrinae lignum, Blumeae folium, Curcumaerhizoma, Imperatae rhizome

Treats disorders of the urinary tract

Beras kencur Sido Muncul Tamarindi pulpa extract, Zingiberis rhizoma extract, Cinnamomi cortex,Kaempferiae rhizoma extract, Oryza sativa

Reduces fatigue, refreshes the body,prevents haemorrhoids and the commoncold, raises stamina and immunity todisease

Kuku Bima Ginseng radix extract, Eurycomae radix extract, Kaempferiae rhizomaextract, Zingiberis rhizoma extract, Zingiberis aromaticae rhizomaextract, Phyllanthi herba extract

Raises mens stamina and libido, andmakes them appear more youthful. Helpsblood circulation, discharging faecesmore easily and reduces the possibility ofatherosclerosis and diabetes

PT. Kimia Farma Fitogas Hypericum extract, Centellae folium extract, Curcumae domesticaerhizoma pulveratum, Curcumae xanthorrhizae rhizoma extract

Relieves digestive disorder symptoms

New Padibu Trigonella foenum graecum, Tribulus terrestris, Yohimbe extract,Talinum paniculatum, Plantago major extract

Treats liver and kidney disturbance

Fitolac Sauropus folium extract Increases and accelerates breast milkproduction

PT. Deltomed Laboratories Srongpas Ginseng Retofracti fructus, Zingiberis zerumbeti rhizoma, Elephantopi radix,Eurycoma radix, Panax ginseng radix extract

Increases vitality, relieves backache, soremuscles, fatigue, and general debility,improves appetite, and nourishes thekidneys

Antangin JRG Zingiberis rhizoma, Panax ginseng extract, Blumeae folia, Menthaefolia, Alstoniae cortex, Myristicae semen

Effectively combats a cold and alleviatesits symptoms such as fever, nausea,bloating, cold sweat, dizziness, andfatigue

PT. Jamu Iboe Jaya Hiperten Orthosiphonis folium, Phyllanthi herba, Plantaginis folium, Blumeaefolium, Centellae herba, Morindae fructus, Alstoniae cortex,Andrographidis herba, Apii herba

Treats mild hypertension

Diabetin Tinosporae caulis, Andrographidis herba, Curcumae rhizoma, Syzigiisemen

Treats diabetes mellitus

PT. Mustika Ratu Tonic tea plus daun dewa dan ginseng Zingiberis aromaticae rhizoma, Zingiberis rhizoma, Panax ginsengradix, Retrofracti fructus, Theae folium, Colae semen, Gynurae folium

Is effective for general healthmaintenance of men and women, goodfor improvement of stamina vitality andbody immunity to make the body fresh, fitand energetic


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Jamu godog bugar ayu Usneae thalus, Zingiberis purpurei rhizoma, Retrofracti fructus, Santalilignum, Sappan lignum, Illicium verum, Kaempferiae rhizoma,Curcumae rhizoma, Foenigraeci semen, Andrographidis herba,Centellae herba, Curcumae domesticae rhizome

Slows the ageing process, improving theblood circulation producing more energyand strength

Jamu Jago Encok Orthosiphonis folia, Zingiberis zerumbeti rhizoma, Zingiberis rhizome Alleviates rheumatismSirnakarang Boesenbergiae rhizoma, Curcumae domestica rhizoma, Curcumae

rhizoma, Orthosiphonis folia, Serycocalycis foliaDissolves kidney stones

Pegal linu Curcumae rhizoma, Eucalipty fructus, Retrofracti fructus, Zingiberiszerumbeti rhizoma, Zingiberis rhizome

Alleviates muscle pains, improvesstamina and avoids lethargy andinsomnia

Esha Eurycomae longifoliae radix, Retrofracti fructus, Piperis nigri fructus,Phyllanthi herba, Zingiberis rhizome

Immunostimulating properties

PT. Jamu Borobudur Allus Piperis folium, Centellae herba, Curcumae domesticae rhizoma,Languatis rhizoma

Nyonya Meneer Jamu sakit Maag Euphorbiae thymifoliae herba, Kaempferiae rhizoma, Caricae folium,Blumeae folium

Treats peptic ulcer

Jamu Akas Jantung Coriandri fructus, Parameriae cortex, Baeckeae folium, Foeniculifructus, Curcumae rhizome

Useful for various coronary problems

Singkir angin Foeniculi fructus, Paederiae folium, Menthae arvensis, Zingiberisrhizoma

Treats the common cold

PT. Air Mancur Jaket pegal linu Zingiberis purpurei rhizoma, Zingiberis rhizoma, Piperis nigri fructus,Saccharum album, Zingiberis aromaticae rhizoma, Languatis rhizoma,Peppermint powder, Foeniculi fructus, Glycyrrhizae radix, Curcumaedomesticae rhizoma, Curcumae rhizoma, Coptici fructus, Alyxiaecortex, Boesenbergiae rhizome

Eliminates fatigue, relieves painfulstiffness of the muscles and joints afterhard work and improves stamina

PT. Martha Tilaar Jamu postnatal Innoshape Sauropi folium, Zingiberis zerumbeti rhizoma, Curcumae rhizoma,Elephantopi folium

Slims down and firms up the body,reducing cellulite, whilst rejuvenatinggenerally

PT. Soho Farmasi Diapet NR Curcumae domesticae rhizoma, Granati pericarpium extract, Psidiifolium extract, Coicis semen, Chebulae fructus extract

Anti-diarrhoea properties

PT. Bintang Toedjoe Encok Siler radix, Zingiberis rhizoma, Anemarrhenae rhizoma, Notopterigiirhizoma, Pterospermi lignum

For treatment of muscle pains

Irex Max Yohimbe bark extract, peppermint oil, Retrofracti fructus, Eurycomalongifolia extract, Ginseng extract

Improves vitality and sexual power

Diami Sausurea radix, Curcumae domesticae rhizoma, Kaempferiae rhizoma,Agastachis herba, Amomi fructus, Atractylodes rhizome

Anti-diarrhoea properties

PT. Konimex Sentia Coptidis rhizhoma, Curcuma domesticate rhizoma Treats stomach pain and diarrhoeaPT. Tenaga Tani farma Pil Binari Catechu, Gallae, Jatrophae curcas folium Inner care for womans healthPT. Puspo Internusa Pacekap diabest Morindae fructus extract, Orthosiphonis folium extract, Syzygii

polyanthi extract, Andrographidis herba extract, Centellae herbaextract, Curcumae rhizoma extract


Perusahaan jamu Sido Jodo Diamanis Plantaginis folium, Swieteniae macrothyllae semen, Syzygii jambolanicortex, Momordicae fructus, Murrayae folium, Ocimi bacillici folium,Curcumae rhizoma, Kaempferiae rhizoma, Melaleucae fructus,Blumeae folium, Caryophylli flos, Catharanthi radix, Alii cepae bulbus,Alstoniae cortex, Andrographidis herba



ed i56 j ournal of herbal m

accepted criteria of safety and efficacy for the protection ofpatients.

4. Jamu as a way of traditional healing

4.1. Rational phytotherapy with jamu andphytomedicine

Jamu, as traditional medicine arising from experiences of thepast and embedded in the culture of society, cannot standstill but constantly changes and develops. Along with conven-tional medicine it shares issues in appropriate and rationaluse. This includes qualification and licensing of the provider,proper use of good quality products, good communicationbetween traditional medicine providers and patients and pro-vision of scientific information and guidance to the public(WHO, 2002). The WHO encourages the use and developmentof traditional medicine as an accessible and affordable meansto provide healthcare for all people (WHO, 2005). Althoughthe pharmacological effects of some jamu constituents havebeen recorded, there is an apparent lack of records or writtendata reporting the effectiveness of jamu medicine, especiallyjamu gendong. To assure the correct use of such products,the Indonesian government (NADFC) has divided the medic-inal plants into three categories based on the way they areprepared and based on a judgement of proof of their effi-cacy; i.e. jamu, standardized herbal medicines, and fitofarmaka(phytomedicines; regulation nr. HK.00.05.4.2411, 2004). Allpreparations have to meet basic safety criteria. The therapeu-tic effects of jamu have to be supported by empirical data. Theefficacy of standardized herbal medicines has to be provedin preclinical trials and standardization on active ingredi-ents is required, while for the efficacy of fitofarmaka, clinicaltrials have to be carried out. The Indonesian governmenthas launched the Centre for Development and Implemen-tation of Traditional Treatment (Sentra P3T) in 1995. TheCentres activities include research on herbal medicines, edu-cation and training of human resources as well as service ofherbalmedicines based treatment. Other programmes includeselecting, testing, certifying, registration/licensing, inventory,screening, clinical testing, utilization and evaluation of tra-ditional medicine, and compilation of laws applicable totraditional treatment.

4.2. Preparation of jamu

Original jamu (jamu gendong) is prepared in the formof a decoc-tion and is sold by ladies carrying jamu on their back. Jamugendong is produced by cottage industries using traditionalmethods. Traditional jamumakers are aware of issues relatingto hygiene, sanitation and chemical contaminations from bio-logical or non-biological sources (such as bacterial and fungaltoxins, heavy metals).

They try to protect raw plant materials and products from

contamination, although this is unlikely to comply with inter-national industrial standards. The methods of preparationare often different from producer to producer, and produc-tion steps like selection of raw materials, sorting, grating,c ine 4 ( 2 0 1 4 ) 5173

scraping, crushing, mixing and cooking, followed by boilingof the plant material in a hygienic way can differ significantly.To ensure public safety it was considered that professionaltraining was necessary to ensure certain standards like iden-tification of the raw materials used in jamu according to theMateria Medika Indonesia (MMI), while for the proof of efficacyof fitofarmaka clinical trials have to be carried out. Jamu mak-ers have to be trained in hygienic productionmethods and theuse of semi-modern techniques such as the small scale extrac-tion methods. The most important aspect of the education byacademic institutions is the introduction of scientific aspectsof jamu. From cottage industries jamu has been developedand is now produced by the industries called IKOT (IndustryKecil Obat Tradisional) and IOT (Industri Obat Tradisional). To pre-pare jamu, IKOT and IOT use modern technologies and theiractivities are based on a scientific approach: not traditionalbut evidence-based, supported with research data. They haveto follow the directions for good manufacturing production(GMP). Today industrially produced jamu is no longer only pre-pared in the form of a decoction but also in the form of atablet, pill, powder, pastille, capsule, extract, cream or oint-ment.

4.3. Legislative aspects of jamu and phytomedicines inIndonesia

The Indonesian government, through the Ministry of Healthand NADFC, is regulating jamu and phytomedicines (fito-farmaka). The regulations are aimed at developing safeherbal medicinal products and to monitor the quality of theproducts including efficacy and efficiency by pharmacovig-ilance reports. For the production of traditional medicinein Indonesia, the jamu gendong and small-scale industrieshave to refer to good manufacturing practice guidelines fortraditional medicine, called CPOTB (Cara Pembuatan Obat Tra-disional yang Baik). CPOTB is regulated by the Ministry ofHealth (regulation nr. 659/MENKES/SK/X/1991). This regu-lation was renewed by BPOM in 2005 with regulation nr.HK.00.05.4.1380. CPOTB and includes all aspects of pro-duction such as raw material, production process, qualitycontrol, factory building, workers, management, instrumen-tation, and sanitation. CPOTB is also to be applied tomanufacturers producing standardized herbal medicines andphytomedicine.

The traditional medicine manufacturers (IOT and IKOT)as well as the jamu products have to be registeredin the BPOM (246/MENKES/Per/V/90 and HK.00.05.41.1384,2005). Using this regulation, the production and distri-bution of traditional medicine can be controlled to fulfilthe requirements according CPOTB. Traditional medicinesare produced in a range of formulations including pow-ders, pills, capsules, crude extracts, tablets and liquids.These medicinal products have to be produced accord-ing to the description published in regulation number661/MENKES/SK/VII/1994. To develop the traditional jamu

medicines, the Indonesian government has establishedthe Centre for Development of Traditional Medicine (Sen-tra P3T). The Centre is supported by regulation number0584/MENKES/SK/VI/1995.


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Table 2 Review of published literature relating to selected medicinal plants used in jamu.

Plant name Plant part Type of extract Major compound(s)or group ofcompounds

Test system (andconcentration/dose)

Results Traditional use of plant

Curcuma domestica Rhizomes Ethanol Curcumin Clinical (180mg per day) Inhibition of DNA polymerase II andinduction of apoptosis (Sharma et al.,2005)

Appendicitis, metritis, tonsillitis,asthma, chancre, rheumatism,anaemia, diarrhoea, hypertension,scabies, dysentry, haemorrhoids

Clinical (120mg per day) Improvement of the morning stiffnessand joint swelling in arthritis patients(Chattopadhyay et al., 2004a,b)

Curcuma xanthorrhiza Ethanol Xanthorrhizol In vitro IC50=40M Inhibition of HIV-I integrase (DeClercq, 2000)

In vitro and in vivoEC50=6.16g/ml

Induction apoptosis (Ismail et al.,2005)

Anorexia, malaria, gastritis,anthelmenthic

Zingiber officinale Rhizomes Ethanol Gingerol, paradol In vitro, in vivo,IC50=40.6g/ml

Induction of apoptosis (Kirana et al.,2003)

Headache, rheumatism, anorexia,cholera, antiemeti, anorexia,influenza, anaemia, malaria,anthelmentic, cough, vertigo

Zingiber aromatica Ethanol Zerumbone In vitro, in vivo,IC50=20.2g/ml

Induction of apoptosis (Kirana et al.,2003)

Kaemferia pandurata Rhizomes Hexane Pinostrobin In vitro 10100g/ml Inhibition of DNA topoisomerase I inhuman tumour cell (Sukardimanet al., 2000)

Dry cough, fungal infectiondiphtheria, gonorrhoea and as aspice in cooking

Chloroform Hydroxypanduratin A In vitro, topical, IC50=84and 12g/ear

Inhibition of TPA induced ear oedemaformation on rats (Tuchinda et al.,2002)

Panduratin A In vitro IC50=5.6M and18.7M

Inhibition of HIV-1 protease activity(Cheenpracha et al., 2005)

In vitro MIC=24g/ml Antibacterial activity against Prevotellaintermedia, P. loescheii, Streptococcusmatans (Park et al., 2005)

Alpinia galanga Rhizomes Oil Ethyl- and ethyl4-methoxy-trans-cinnamate

In vitro 20mg per 2 days Induction of glutatione S-transferase(GST) (Zheng et al., 1993)

Stomachic, anorexia, dermatosis,malaria, gastritis

Aqueousacetone

l-Acetoxychavicol and1S-1-Acetoxyeugenolacetate

In vivo 2mg/kg BW Induction of apoptosis (Ichikawa et al.,2005)

In vitro IC50=15 and19M

Increase of the glutathione (GSH)levels of gastric mucosa in rats(Matsuda et al., 2003a,b)


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Inhibition of -hexosaminidase, as amarker of antigen-IgE-mediateddegranulation (Matsuda et al., 2003a,b)

Rheum palmatum Root Methanol Pulmatin andchrysophaneinphyscionin

In vitro IC50=1.5g/ml2.5g/ml

Inhibition of the growth HeLaepithelioid and BT-20 human breastcarcinoma cells (Kubo et al., 1992)

Skin softening, stomach-ache, tonic

4-O-methylpiceid andrhapontin

In vitro IC50=280g/mland 600g/ml

Inhibition of -glucosidase activity(Kubo et al., 1991)

Cymbopogon citrates Leaves Oil d-Limonene andgeraniol

In vitro 20mg per 2 days Induction of glutatione S-transferase(GST) (Zheng et al., 1993)

Dysuria, diaphoretic, oedema,common cold, rheumatism,gastritis, enteritis

Geranial, neral,myrcene, -pinene

In vivo 500mg/kg BW Growth inhibition of Plasmodiumberghei 86.6% (Tchoumbougnang et al.,2005)

Plumeria bicolour Bark Methanol Plumieride In vitro, IC50=49.5g/ml Inhibition of the growth RIF tumourcell lines (Dobhal et al., 2004)

Dysuria, malaria, syphilis, purgative,fever,oedema

Alstonia scholaris Stem bark Ethanol Echitamine In vivo 180mg/kg bodyweight

Increase of the killing effect ofberberine against tumour on Ehrlichascites carcinoma (EAC)-bearing mice(Jagetia and Baliga, 2004)

Fever, dermatosis, anorexia,nephritis, malaria, lowering of bloodpressure

In vitro, ED50=2.5g/ml Cytotoxic effect in HeLa cell (Jagetiaand Baliga, 2005)

Aqueous,ethanol

Alkaloid In vivo 50100mg/kg BW Stimulation of non specific immuneresponse (Iwo et al., 2000)

Cuminum cyminum Seeds Ethanol Essential oil In vivo, 160mg/g diet Increase of GST activity, inhibithepatocarcinogenesis (Aruna andSivaramakrishnan, 1998)

Stimulant, stomachic, gastric ulcer

Fruits In vivo ED50=0.12ml/kg Exhibition of anticonvulsant activityin both PTZ- and MES-inducedseizures (Sayyah et al., 2002)

Andrographis paniculata Aerial part Ethanol 14-Deoxyandrographolide14-Deoxy-11,12-didehydroandrographolide

In vitro ED 50=2.8g/ml1.5g/ml

Exhibition of the cytotoxic activityagainst human T-47D cell line (Tanet al., 2005)

Tonsillitis, chancre, antidote formany poisonings. Typhus, fever,diabetes, tonic, dysentery, eardiseases, eczema, appendicitis,common cold, diphtheria,depurative, epilepsy, gonorrhoea,syphilis, dandruff

Andrographolide Clinical 5mg/kgbodyweight (BW)

Inhibition of HIV induced cell cycledisregulation (Calabrese et al., 2000)

In vivo 1.5mg/kg BWIn vitro IC50=4g/ml

Reduction of the plasma glucose levelin streptozotocin-induced diabeticrats (Yu et al., 2003)


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Roots Chloroform Xanthone Antiplasmodial activity againstPlasmodium falciparum (Dua et al., 2004)

Ethanol In vivo 30mg/kgLeaves Andrograpanin In vitro 3M Enhancement of chemokine stromal

cell-derived factor-1 alpha (SDF-1alpha) induced chemotaxis (Ji et al.,2005)

Arcangelisia flava Whole part Berberine In vitro, 25M Inhibition of the growth of humanHepG2 cells (Chi et al., 1994)

Jaundice, stomachic, anthelmentic

Ardisia compressa Leaves Aqueous Phenolic compounds In vivo, IC50=47g/ml Inhibition of hepatocarcinogenesis(De Mejia and Ramirez, 2004)

Fever, diarrhoea, cough

Phyllanthus species Whole plants Aqueous Alkaloids, flavonoids,lignans and terpenoids,tannins

Clinical 1.5 g per day Antihepatitis B through prevention ofALT flares, progression to cirrhosisand/or liver cancer, and ultimatelyprolong survival (Liu et al., 2001)

Wound healing, asthma, epilepsy,malaria, constipation, loweringblood pressure, menstrual disorders,tetanus, diarrhoea, convulsant

Elargic acid, lignans,quercetin, lupeol

In vitro and in vivoIC50=1.3g/ml

Anti-HIV activity blocked theinteraction of HIV-1 gp120 with itsprimary cellular receptor CD4 at 50%inhibitory (Notka et al., 2004)Antiplasmodial activity against P.falciparum (Tona et al., 2004)

Piper sarmentosum Berries Methanol Sarmentine, 1-piperetylpyrrolidine

In vitro IC50=18.9g/mlIC50=6.5g/ml

Antiplasmodial activity against P.falciparum (Rukachaisirikul et al., 2004)

Cough, asthma

Piper caba Aqueousacetone

Piperine, piperanine,pipernonaline

In vivo 25mg/kg BW Inhibition of ethanol- andindomethacin-induced gastric lesions(Morikawa et al., 2004)

Diaphoretic, oedema lowering bloodpressure diaphoretic, dyspnoea

Piper longum Ethanol Piperine In vitro IC50=7.0M Inhibition of monoamine oxidase andantidepressant like activity (Lee et al.,2005)

Piper nigrum Isobutyleicosatrienamide,trachyone,pergumidiene

In vitro MIC=70, 60,58M

Inhibition of the growth of B. subtilis,B. sphaericus, S. aureus Klebsiellaaerogenes and Chromobacteriumviolaceum (Reddy et al., 2004)

Glycyrrhiza glabra Roots Ethanol Isoliquiritigenin In vitro 1g/ml Inhibition of reductase activity andplatelet aggregation (Tawata et al.,1992)

Rheumatic

Liquiritin apioside,liquritin andliquiritigenin

In vivo 30mg/kg BW Antitussive (Kamei et al., 2005)


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Eurycoma lancifolia Roots Methanol Eurycomanone7-methoxy--carboline-1-propionicacid

In vitro IC50=1.9g/mlIC50=2.1g/ml

Antiplasmodial activity (Kardonoet al., 1991)

Fever, depurative, dysentery, aphtha,tonic, anorexia

Anacardium occidentale Stem barks Aqueous In vivo 800mg/kg BW Inhibition of the fresh eggalbumin-induced acute inflammation(Ojewole, 2004)

Purgative, aphtha, dermatosis

Hexane Stigmast-4-en-3-ol andstigmast-4-en-3-one

In vivo 1.5mg/kg BW Hypoglycaemic activity in normal,healthy dogs (Alexander-Lindo et al.,2004)

Anacardic acid In vitro MIC=6.25g/ml Inhibition of -lactamase (Bouttieret al., 2002)

Abelmoschus moschatus Aerial parts Buthanol Myricetin In vivo EC50=0.1M Reduction of the plasma glucose levelin streptozotocin-induced diabeticrats (Liu et al., 2005)

Convulsant, stomachic, aphrodisiac,itch

Aloe vera Leaves Ethanol In vivo 200mg/kg BW Reduction of the plasma glucose levelin streptozotocin-induced diabeticrats (Rajasekaran et al., 2004)

Haemorrhoid, anthelmen-tic,diabetes, cough, gonorrhoea,tuberculosis

Centella asiatica Aerial parts Aqueous Asiaticoside In vivo 10mg/kg BW Enhancement of gastric ulcer healing(Cheng et al., 2004)

Stomachic, anorexia, woundhealing, chancre, bronchitis,dysentery, cough

Polysaccharide In vitro 100g/ml Enhancement of the proliferation of Tand B lymphocytes (Wang et al., 2005)

Orthoshipon aristatus Leaves Aqueous Pimarane-typediterpenes,neoorthosiphols A and B

In vitro IC50 15.2 and60.1nmol/ml

Inhibition of the contractile responsein rat thoracic aorta smooth muscle(Ohashi et al., 2000a,b)

Laxative, haemorrhoid, dysentery,diarrhoea, colitis, menstrualdisorder, stomachic,cholecystopathy

MethylripariochromeneA

In vivo IC50=23.8g/ml Decrease of systolic blood pressure inconscious stroke-pronespontaneously hypertensive rats(Ohashi et al., 2000a,b)

Coriandrum sativum Fruits Essential oil Terpenoids In vitro MIC 0.87mg/ml Inhibition of the growth ofEscherichia coli, Bacillus megaterium,Pseudomonas, Erwinia, Xanthomonas,Agrobacterium (Lo Cantore et al., 2004)

Stomach ache, vertigo, emetic,stomachic, aphtha, menstrualdisorders


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. Biological activity of the most commonlants in jamu

he biological activities of the most common plants used inamu as reported in the literature are summarized in Table 2.hese are discussed in more detail in the following sections.

.1. Anticancer

lants from the family Zingiberaceae are the most frequentlysed ingredient of jamu. Eleven Curcuma species (Curcumaeruginosa, C. aurantiaca, C. colorata, C. domestica (synonym:. longa), C. euchroma, C. mangga, C. petiolata, C. purpurascens,. soloensis, C. xanthorrhizae, and C. zedoria) have been usedraditionally as a spice and to treat several illnesses suchs appendicitis, asthma, itch, rheumatism, abdominalgia,naemia, hypertension, diarrhoea, and dysentery (Hatchert al., 2008). Curcumin is the main phenolic constituent ofhe genus especially in the rhizoma of tumeric (C. domestica).lthough C. domestica also known as C. longa, has not tra-itionally been used for anti-carcinogenic purposes, recentnvestigations show that this plant has promising effects inhis area,mainly to be ascribed to curcumin (Gupta et al., 2012).he anticarcinogenic mechanism of action of curcumin haseen partly elucidated. Inducing apoptosis plays an impor-ant role. Furthermore, it reduces the cell cycle progressionhereby preventing cancerous cell growth (Chattopadhyayt al., 2004a,b; Karunagaran et al., 2005). In vitro (in cancer cells)nd in vivo (in animal models), it suppressed carcinogenesisf the liver, kidney, colon, and breast (Okazaki et al., 2005;irana et al., 2003). Preclinical and clinical studies with cur-umin in relation to its anticarcinogenic potential have beeneviewed. Human clinical trials indicated no dose-limitingoxicity up to 10 g/day taken orally. The studies revieweduggest that curcumin has potential in the prevention andherapy of cancer (Agarwal et al., 2003; Sharma et al., 2005). C.anthorrhizaused traditionally as an antibacterial, anticarcino-enic and anti-inflammatory agent has been shown to exhibitntiproliferative and anticarcinogenic activities. These activ-ties are largely attributed to the sesquiterpene compoundanthorrhizol isolated from this plant which was observedo significantly increase apoptosis in HeLa cells (Ismail et al.,005).Ginger (Zingiber officinale Rose) which contains the phenolic

etones gingerol and paradol has been launched in Indonesias fitofarmaka (HMP or phytomedicine) for malignancies (anti-eoplasma). It has been licensed as a standardized herbaledicine in Indonesia for this indication and has proven

he activity. Anti-carcinogenic activity of the ginger ethanolicxtract has been reported in vitro (to human colon cancernd breast cell cancer cell lines) and in vivo (in rats). Thetrongest anticancer carcinogenic activity has been shownor another Zingiberaceae species, Zingiber aromaticum (Kiranat al., 2003; Manju and Nalini, 2005). It has been suggestedhat Z. aromaticum containing the sesquiterpene zerumbone

lso has the potential to be developed as HMPwith anticarcio-enic properties because of apoptosis induction. Panduratin,chalcone derivative isolated from Kaemferia pandurata, alsomember of the Zingiberaceae family rhizoma has beenine 4 ( 2 0 1 4 ) 5173 61

reported to suppress carcinogenesis in human colon cancercell lines (Kirana et al., 2003; Yun et al., 2005). Pinostrobin,a flavonoid from this plant showed cytotoxic activity againsthuman mammary carcinoma cells (Sukardiman et al., 2000).Ethyl trans-cinnamate and ethyl 4-methoxy-trans-cinnamatefrom galanga root oil (Alpinia galanga) induced the activityof the detoxifying enzyme, glutathione S-transferase (GST),a major mechanism for chemical carcinogen detoxification(Zheng et al., 1993). Another isolated compound from thisplant, 1-acetoxychavicol acetate has been found to suppresschemical- and virus-induced tumour initiation and promo-tion. Although the mechanism is not fully understood, thiscompound inhibits activation of NF-B and NF-B-regulatedgene expression. This may explain its ability to enhance apo-ptosis and to inhibit tissue invasion (Ichikawa et al., 2005).

Isolated compounds from plants used in jamu, includingZingiberaceae species, showed anti-oxidative activity in vitrousing H4IIE rat hepatoma cells. Kaempferol and luteolinprotected these cells against oxidative stress. The abilityof kaempferol and luteolin to inhibit oxidative DNA strandbreaks supports their suggested role as protective agentsagainst diseases such as cancer (Steffan et al., 2005). Threeanthraquinone glycosides (pulmatin, chrysophanein andphyscionin) isolated from Rheum palmatum roots exhibitedmoderate cytotoxic activity against HeLa epitheloid cells andinhibited the growth of BT-20 human breast carcinoma cells(Kubo et al., 1992). The in vitro cytotoxicity of the plumieride,an iridoid compound which was isolated from methanolextract of the bark of Plumeria bicolor and several analogueswas determined in radiation-induced fibrosarcoma (RIF)tumour cells. The analogues gave stronger activity thanplumieride itself (Dobhal et al., 2004). An ethanolic extractof the bark of Alstonia scholaris enhanced the anticanceractivity of berberine in Ehrlich ascites carcinoma-bearingmice. This extract also showed cytotoxic activity to HeLacells. Compared to the active principle echitamine, present inA. scholaris, the bark extract was more effective against HeLacells (Jagetia and Baliga, 2004, 2005). The cytotoxic activity ofthe extract was shown to depend on the season of collectionof the plant bark. The extract of bark collected in the summerseason has the highest activity (Jagetia and Baliga, 2004, 2005).Usually plants to be used in jamu are collected during the dryseason (also considered as the summer season). Andrographispaniculata also called sambiloto by native Indonesians hasbeen intensively investigated for its anticarcinogenic activity.The diterpenoid compounds 14-deoxyandrographolide and14-deoxy-11,12-didehydroandrographolide isolated from theaerial parts of this plant showed marked activity againsta human breast carcinoma cell lines (T-47D, Hs-578T) (Tanet al., 2005). The consumption of Ardisia compressa tea(aqueous extract) resulted in complete inhibition of thechemically induced hepatocarcinogenesis in Wistar rats(De Mejia and Ramirez, 2004). Catharanthus roseus that hasbeen used to treat cancer (e.g. leukaemia, lymphoma, breastcancer, long cancer, Hodgkins disease) (Cragg and Newman,2005) contains the clinically used anticancer compounds

vincristine, vinblastin and other vinca alkaloids (Cragg andNewman, 2005). Awater extract ofCentella asiatica significantlyreduced the multiplicity of neoplasms in the small intestineof male F344 rats suggesting that C. asiatica may have a


62 j ournal of herbal med ic ine 4 ( 2 0 1 4 ) 5173

H3CO

HOOH

OCH3

O OO

O

HOHO

HO

O

O

HOHO

OR1R3O

OR2

O

CO2CH3O

OO

COOR4

OR2OR1

O

CO2CH3

HO

HO

HO

HO

OHHO

OHOH

O

COOR3

CO2CH3

OH

OH

HO

HO

HOH2C

O

O

O

O O

O

HOOH

OH

HOOH

OHOH

OHOH

O

O

H3COOCH3

R2O

R1O

BzOBzO

OAcOH

O NH

N CH3

HOH2C CO2CH3

HO

3

1 2

4. R1 = R2 = R3 = H5. R1 = R2 = H, R3 = CH3

11. R1 = R2 = CH3, R3 = R4 = X12. R1 = H, R2 = CH3, R3 = R4 = X13. R1 = R2 = R3 = CH3, R4 = X14. R1 = R2 = CH3, R3 = X, R4 = CH315. R1 = H, R2 = CH3, R3 = R4 = X

16. R1 = CH3, R2 = H, R3 = X, R4 = CH3

X =

6

7 8. R1 = OH, R2 = Ac9. R1 = Ac, R2 = OH

+

10

Fig. 1 Chemical structure of several active compounds from plants used in jamu; andrographolide (1),14-deoxyandrographolide (2) (Andrographiis paniculata), curcumin (3) (Curcuma domestica), hydroxypanduratin A (4),panduratin A (5) (Kaempferia pandurata), asiaticoside (6) (Centela asiatica), methylripariochromene A (7), orthosiphol A and B(8 and 9) (Orthoshipon aristatus), echitamine (10) (Alstonia scholaris), helicterins AF (1116) (Helicteres isora).


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hemopreventive effect on colon tumorigenesis (Bunpo et al.,004). 2-Hydroxycinnamaldehyde isolated from Cinnamomumassia bark, strongly inhibited the in vitro growth of a broadanel human cancer cells and the in vivo growth of the SW-620uman tumour xenograft (Lee et al., 1999). Coriandrum sativumas shown to act protectively against the deleterious effectsf disturbance of the lipid metabolism in experimental colonancer in rats (Chithra and Leelamma, 2000) (Fig. 1).Ganopoly, an aqueous polysaccharide fraction extracted

rom the fruiting bodies of Ganoderma lucidum has antitu-or activity ascribed to immunomodulating activity (Takarat al., 2005) and is a recent addition to the jamu materiaedica. A similar effect has occurred with other traditionallysed jamu plants. Ganopoly significantly reduced the tumoureight in a dose-dependent manner in mice, with inhibitionates of 32.3, 48.2, and 84.9% at doses of 20, 50, and 100mg/kg,espectively. It may represent a novel promising immunother-peutic agent or a lead for cancer treatment (Gao et al., 2005).mmunomodulating effects that may be useful in the treat-ent of cancer have been reported for ethanolic extracts oferial parts of Phyllanthus niruri (Maat, 2002). The combinationf anticancer drugs such as paclitaxel with herbal extracts e.g.rom Glycyrrhizae radix, Rhei rhizoma, Scutellariae radix, Zizyphiructus and Zingiberis rhizoma enhanced the paclitaxel sensi-ivity in HeLa cells via the inhibition of multidrug resistancey inhibiting cellular mechanisms that underlie multidrugesistance (e.g. P-glycoprotein (P-gp)). These extracts, in a con-entration dependent way, suppressed the growth of HeLaells (human ovarium carcinoma cell line). The results con-luded that the combination of anticancer drugs with someerbal extracts contributes to the improvement of clinical out-omes in cancer chemotherapy (Takara et al., 2005). Alkaloidsnd quassinoids from Eurycoma longifolia, iridoids and lignansrom Plumeria rubra showed cytotoxic activity to humanbreast,olon, fibrosarcoma, lung, melanoma, KB, KB-V1 cancer cellines and in murine lymphocytic leukaemia (Kardono et al.,990, 1991). The cytotoxic and antitumor activities of plantssed in jamu as reported in the literature, are further summa-ized in Table 1.

.2. Antiviral

any of the medicinal plants used in jamu have been testedor antiviral activity in vitro and in vivo, there is however aaucity of rigorous clinical trials. The methanolic extracts oflants used in jamu e.g. A. paniculata, Swietinia mahagoni and C.eruginosa showed anti-HIV activity using HIV-I-infected MT-cells. With the dose range of 4.2175g/mL they inhibited

he HIV-protease (Otake et al., 1995). Methanolic extractsf Melaleuca leucadendron fruit and Annona muricata stem-ark collected in Indonesia have been reported to be activegainst herpes simplex virus-1 in vitro (Padma et al., 1998).. leucadendron significantly prolonged the development oferpes-related skin lesions in a mouse HSV-1 infection assaynd reduced their mortality (Padma et al., 1998; Nawawi et al.,999). Aqueous extracts, tannins, lignans and other isolated

ompounds from Melaleuca and Annona species have beenested for their anti-HIV activity in vitro and in vivo. Theynhibited the HIV-key enzymes e.g. integrase, reverse trans-riptase and protease (Calixto et al., 1998; Notka et al., 2004).ine 4 ( 2 0 1 4 ) 5173 63

The genus Phyllanthus has been intensively studied clinicallyfor its antiviral effects. A systematic review of 22 randomizedclinical trials showed that Phyllanthus species have positiveeffects on antiviral activity and exhibit positive effects onliver biochemistry in chronic hepatitis B virus infection (Liuet al., 2001; Calixto et al., 1998). A. paniculata was also clin-ically tested for its antiviral activity. A phase I clinical trialof andrographolide isolated from A. paniculata was conductedin 13 HIV positive patients and five HIV uninfected, healthyvolunteers. This trial concluded that andrographolide mayinhibit HIV induced cell cycle deregulation, leading to a risein CD4 (+) lymphocyte levels in HIV-1 infected individuals(Calabrese et al., 2000). Helicterins AF, dimeric (7.5,8.2)-neolignans with a bicyclo[2.2.2]octene C-framework isolatedfrom Helicteres isora showed a mild inhibitory activity againstreverse transcriptase from avianmyeloblastosis virus (Tezukaet al., 2000).

5.3. Antimalarial and antiparasitic

Most of the plants mentioned here have been traditionallyused as antimalarial agents in Indonesia. Methanolic extractsprepared from the stems and bark of A. scholaris, Alstoniamacrophylla and Alstonia glaucescense have been assessed forantiplasmodial activity against multidrug-resistant K1 strainof Plasmodium falciparum cultured in human erythrocytes. Theactive bisindole alkaloids, e.g. villalstonine, macrocarpamine,from these extracts, in contrast to chloroquine (antimalar-ial medicine), had a significantly higher affinity to the K1strain than to the T9-96 strain (Keawpradub et al., 1999).1,2-Dihydroxy-6,8-dimethoxy-xanthone, isolated from A. pan-iculata possessed in vitro activity against P. falciparum. In vivoit showed antiplasmodial activity and gave a reduction (62%)in parasitemia after treating the Swiss Albino mice infectedwith Plasmodium berghei (Dua et al., 2004). The petroleum etherextracts of the rind of Carica papaya and Citrus sinensis alsoshowed antimalarial activity against strain P. falciparum FCK2 in vitro (Bhat and Surolia, 2001). Screening of plant extractsthat are traditionally used for the treatment of malaria in Javashowed strong antimalarial and antibabesial activitiy. Theyinclude Achillea millefolium, Baeckea frutenscens, Brucea javan-ica, C. xanthorrhiza, Strychnos lucida, Swietenia macrophylla andP. niruri (Trimurningsih et al., 2005; Subeki et al., 2005a,b).Antibabesial activity was also found for protoberberine alka-loids and 20-hydroxyecdysone from Arcangelisia flava againstBabesia gibsoni (Subeki et al., 2005a,b). In principle B. gib-soni infects canines (dogs), but it may have relevance forother zoonosis as well. An in vitro study on traditionallyused malaria remedies in the Kenyah of the Apo Kayan,East Kalimantan (a remote forested plateau in IndonesianBorneo) concluded that plants such as Lansium domesticumand C. papaya are more likely to be effective antimalar-ials. These herbal remedies were found to have activityagainst chloroquine-resistant P. falciparum (Leaman et al.,1995). Eurycomanone and 7-methoxy--carboline-1-propionic

acid from E. longifolia, triterpenoid lansioides from L. domes-ticum, and leaf extract of Azadirachta indica collected fromKalimantan demonstrated significant antimalarial activity(Kardono et al., 1991; Omar et al., 2003).


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5.4. Anti-inflammatory, antirheumatic, antipyreticand analgesic

The anti-inflammatory effects of the methanol extract fromMorinda officinalis (noni or mengkudu) in vitro and in vivohave been shown by inhibition of the production of nitricoxide, prostaglandin E-2 and tumour necrosis factor-alpha inlipopolysaccharide-stimulated RAW 264.7 macrophages (Kimet al., 2005a,b). Anti-inflammatory effects were determinedin rats using the carrageenan oedema model. Antinociceptiveactivity was determined inmice using the acetic acid-inducedabdominal constriction test and the hot plate test. The inhi-bition of the prostaglandin E2 production in CaCo2 cells hasbeen also shown by Aloe vera gel. Another effect of A. verawasthe inhibition on reactive oxygen metabolites in the humancolorectalmucosa biopsies. This findingmay have a therapeu-tic relevance in inflammatory bowel disease (Langmead et al.,2004). An aqueous extract of tempe (fermented soya-beans)which is a popular food in Indonesia has been reported to haveanti-inflammatory, antioxidant and antithrombotic activity inan experimental photochemical thrombogenesis model usingrat femoral artery (Rilantono et al., 2000). Cinnamomum cortexthat was collected in Indonesia inhibited the rise in vascularpermeability and oedema induced by acetic acid, carrageenin,serotonin and arachidonic acid in mice. The effect was alsoshown on secondary lesions in the development of adjuvant-induced arthritis (Kubo et al., 1996). Hydroxypanduratin Aand panduratin A isolated from K. pandurata rhizoma showedsignificant topical anti-inflammatory activity in the assay ofTPA-induced ear oedema in rats. The presence of these com-pounds may very well be related to the uses of this plantin traditional medicine, to treat colic disorder, fungal infec-tions, dry cough, rheumatism and muscular pains (Tuchindaet al., 2002). The lignans niranthin, phyltetralin and nirte-tralin isolated fromaerial parts of Phyllanthus amarus exhibitedmarked anti-inflammatory properties in vitro suggesting thatthese lignansmaybe themainactiveprinciples responsible forthe traditional application of this plant for anti-inflammatoryproperties (Kassuya et al., 2005). The screening of 75 medic-inal plants collected in Indonesia showed that many ofthem had inhibitory effects on nitric oxide (NO) productionin lipopolysaccharide-stimulated RAW264.7 macrophages aswell as antioxidant activity through the evaluation of free rad-ical scavenging effect and reducing power (Choi and Hwang,2005). NO is widely recognized as an important messengerand effective molecule in a variety of biological systems. TheNO production is inhibited by nitric oxidase inhibitors thatcan be used as therapeutic agents for inflammatory diseases(Tinker and Wallace, 2006). Chrubasik et al. (2005) compre-hensively reviewed the effects of an ethanolic extract ofginger (Z. officinale rhizoma) and its efficacy profiles in vitro,in vivo (in laboratory animals) and in clinical studies. Gingerextracts (50 g ginger daily) for musculoskeletal pain resultedin some pain relieving effects. His review, however, suggestedthat further studies were needed to establish efficacy andto find an optimum dosage of ginger preparations for thetreatment of osteoarthritic pain. The ethanolic extract of

ginger (Z. officinale) together with A. galanga, C. longa, Camel-lia sinensis and Uncaria tomentosa also showed a statisticallysignificant effect on reducing knee pain in patients withc ine 4 ( 2 0 1 4 ) 5173

osteoarthritis (Altman and Marcussen, 2001; Ahmed et al.,2005).

5.5. Hepatoprotective

Herbal preparations containing Andrographis panuculata and P.amarus for various liver disorders have been shown to haveantihepatotoxic activity (Ram, 2001). The ethanolic extract andisolated diterpenes andrographolide and neoandrographolidefrom the aerial parts of A. paniculata showed significantantihepatotoxic action in P. bergheiK173-inducedhepatic dam-age in Mastomys natalensis (multimammate rats) (Chanderet al., 1995). A hepatoprotective effect of ethanolic extractsof turmeric together with sesquiterpene and curcuminoid-containing fractions has been shown to be related to thesuppression of alanin and aspartate aminotransferase andlactate dehydrogenase level on d-galactosamin induced liverinjury in rats (Miyakoshi et al., 2004). The levels of certainenzymes in the blood are a measure for the liver function.Changes in these levels may indicate liver function disorder.The hepatoprotective effect ofA. scholaris bark on liver injuriesinduced by the carbon tetrachloride (CCl4),-d-galactosamine,acetaminophen and ethanol were investigated by meansof serum-biochemical and histopathological examinations.Ethanolic extracts of A. scholaris bark significantly lowered-d-galactosamine induced serum transaminases elevationin the serum biochemical analysis in rats (Lin et al., 1996).CCl4-induced hepatotoxicity in the liver of rats, as judged bythe raised serum enzymes, glutamate oxaloacetate transami-nase and glutamate pyruvate transaminase, was prevented bypretreatment with the extracts of P. niruri, demonstrating itshepatoprotective action (Harish and Shivanandappa, 2006).

5.6. Antidiabetic

Diabetesmellitus is recognized by chronic elevation of the glu-cose level in the blood and often accompanied by symptomsof severe thirst, polyuria, weight loss, and stupor. Medic-inal plants that are used clinically to treat diabetes haveshown their antidiabetic activity in vitro, in vivo (in animalmodels) and in clinical studies. The methanolic and aque-ous extracts derived from A. galanga caused highly significantreduction in the blood glucose levels of normal rabbits (Akhtaret al., 2002). The glucosidic compounds 4-O-methylpiceidand rhapontin, isolated from kelembak (R. palmatum) rootsthat were collected from the market in Indonesia exhibitedmoderate -glucosidase inhibitory activity in vitro. The inhi-bition of -glucosidase activity may be effective in controllingabnormal levels of blood glucose in metabolic diseases suchas diabetes (Kubo et al., 1991). Hypolipidemic effects havebeen shown for aqueous extracts of cumin seeds (Cuminumcyminum) on alloxan-induced diabetic, triton and cholesterolfed hyperlipemic rats. Hyperlipidemia is an associated com-plication of diabetes mellitus. In this study, administeringa cumin extract to diabetic rats significantly reduced theirblood glucose levels. The mechanism may be a potentiationof insulin from the cells (Dhandapani et al., 2002). Guazumaulmifolia leaves and Trigonella fonum graceum seeds that areused clinically against diabetes mellitus have been studied


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or their antihyperglycemic effect. Aqueous extract of theselants reduced blood glucose levels in the rabbits, pointingt a hypoglycemic activity of the extract (Alarcon-Aguilarat al., 1998). G. lucidum, the water and ethanol extracts of Piperetle and dianex, a polyherbal formulation consisting of thequeous extracts of Gymnema sylvestre leaves, Eugenia jam-olana seeds,Momordica charantia fruits, A. indica leaves, Cassiauriculata flowers, Aegle marmelose fruits, Withania somniferaoots, and C. longa rhizoma had hypoglycemic activity in nor-al and streptozotocin-induced diabetic mice and rats (Yangt al., 2004; Mutalik et al., 2005; Arambewela et al., 2005). Mostf those plants are used in jamu. Preclinical evaluation con-isting of animal studies, acute and subacute toxicity testingnd evaluation of the antidiabetic effect of E. jambolana seedowder in streptozotocin-diabetic rats was adequate for thepproval to start phase 2 clinical trials to evaluate this seedowder as a complementary therapy in patients with typeand type 1 diabetes. The study showed that E. jambolanaossibly acts as a hypoglycemic agent by increasing insulinevels, but it remains unclearwhether type 1 or type 2 diabetesre indicated. Toxicity studies in rats showed no evidence ofortality or abnormality (Sridhar et al., 2005). The total triter-enoid fraction isolated from the aerial parts of C. asiatica, haseen studied in diabetic patients withmicroangiopathy. It washown that this fraction is useful in diabetic microangiopa-hy by improving microcirculation and decreasing capillaryermeability and protected against the deterioration ofmicro-irculation due to diabetic microangiopathy (Cesarone et al.,001).

.7. Antimicrobial and antifungal

ntibacterial and antifungal activities have been shown byqueous extracts plus andrographolide and arabinogalactanroteins isolated from A. paniculata which were comparablein terms of growth inhibition of Bacillus subtilis, Escherichia coli,seudomonas aeruginosa and Candida albicans) to some knownntibiotics, streptomycin, gentamycin and the antifungalystatin (Singha et al., 2003). Extracts of A. scholaris, Anac-rdium occidentale (hexane), and C. papaya seeds (methanol andutanol) have been reported to possess a broad spectrum ofntibacterial activity (Bouttier et al., 2002; Khan et al., 2003;awkins et al., 2003). Remarkably, plants or plant extracts dis-laying toxicity to bacteria or fungi frequently show toxicityn other in vitro systems. Apparently there is an underlyingeneral mechanism of toxicity responsible for this. This isllustrated by an ethanolic extract of C. papaya seeds thataused elevation of rat serum levels of acid phosphatase (ACP),lkaline phosphatase (ALP), and aspartate amino transferaseAST). Also mild to severe metaplasia of hepatocytes wasevealed in a dose-related manner as well as proliferation ofupfer cells andhepatic cells cirrhosis. These biochemical andathological changes indicated liver cell damageandmalfunc-ion (Udoh and Udoh, 2005).

The growth-inhibiting activity of cinnamaldehyde isolatedrom C. cassia towards human intestinal bacteria (Clostridium

erfringens, Bacteroides fragilis and Bifidobacterium bifidum)as shown using an impregnated paper disc method andompared with that of tetracycline and chloramphenicol (Leend Ahn, 1998). The essential oils of C. sativum and Foeniculumine 4 ( 2 0 1 4 ) 5173 65

vulgare were reported to possess antibacterial activity to E.coli and Bacillus megaterium in vitro. The essential oil from C.cyminum and the isolated compounds, p-mentha-1,4-dien-7-al, cumin aldehyde, -terpinene, and -pinene, showedantibacterial activity against the genera Clavibacter, Curto-bacterium, Rhodococcus, Erwinia, Xanthomonas, Ralstonia, andAgrobacterium (Lacobellis et al., 2005). The essential oils fromCymbopogon citratus, C. nardus, and Cymbopogon schoenanthusshowed a fungistatic effect against superficial mycosis (Kobaet al., 2003). The essential oil of Cinnamomum burmanni (barkand leaves) and Tagetes erecta (leaves) that were collectedin Indonesia have been reported to exhibit antimicrobialactivity against B. subtilis and Salmonella typhimurium andantifungal activity against C. albicans in vitro (Sukandar et al.,1999; Hartati et al., 1999). An ethyl acetate extract of C. longahas been reported to have antibacterial activity and thepotential to restore the effectiveness of -lactams againstmethicillin-resistant Staphylococcus aureus (MRSA), and inhibitthe MRSA invasion of human mucosal fibroblasts (Kim et al.,2005a,b). A study of Indonesian plantswith ethnomedical usesshowed that the methylene chloride and methanolic extractsof Terminalia catappa, S. mahagoni, Phyllanthus acuminatus,Ipomoea spp., Tylophora asthmatica and Hyptis brevipes haveantibacterial activities against E. coli, S. aureus, Xanthomonascampestris and B. subtilis and antifungal activities against C.albicans, Pythium ultimum, Rhizoctonia solani and Sclerotiumrolfsii (Goun et al., 2003). The ethanolic extracts from severalplant species belonging to the Zingiberaceae family used inKenyah (Indonesian Borneo), especially A. galanga, Curcumazedoaria and Zingiberis purpureum, were found to have pro-nounced inhibitory activities against a wide variety of humanpathogenic fungi, including strains resistant to the commonantifungals amphotericin B and ketoconazole. As members ofthe Zingiberaceae are generally regarded as safe for human con-sumption, these species are excellent candidates for furtherdevelopment as medicinal plant products (Ficker et al., 2003).

5.8. Gastroprotective

Isolated compounds, 1S-1-acetoxychavicol acetate and 1S-1-acetoxyeugenol acetate, from A. galanga markedly inhibitedthe ethanol-induced gastric mucosal lesions in rats. Theaction of 1S-1-acetoxychavicol was attenuated by pre-treatment with indomethacin and N-ethylmalcimide andsignificantly increased the glutathione (GSH) levels of gastricmucosa in rats. GSHacts as anantioxidant and is important formaintaining the mucosal integrity in the stomach (Matsudaet al., 2003a,b). A different mechanism of hepatoprotectiveactivity was shown by asiaticoside, an active triterpenoidconstituent of leaves of C. asiatica. They were found to pro-mote angiogenesis and stimulate blood vessel formation andmucosal cell regeneration during the gastric ulcer healingstage that are important aspects of the wound healing pro-cess. Angiogenesis in granulation tissues improves circulationto the wound site thus providing oxygen and nutrients essen-tial for the healing process (Cheng et al., 2004). The effect

of an ethanolic extract of A. vera on acute gastric mucosallesions induced by 0.6M HCl and acid output was studied inpylorus ligated and lumen perfused rats, respectively showingthat A. vera has gastric acid anti-secretory activity and thus


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could potentially protect the gastric mucosa at low concen-trations against injurious agents (Yusuf et al., 2004). Morindacitrifolia (noni) inhibits gastric emptying in male rats via amechanism involving stimulation of cholecystokinin and itsreceptor activation. Cholecystokinin is a peptide hormone ofthe gastrointestinal system responsible for stimulating thedigestion of fat and protein. It delays gastric emptying andinhibits gastric acid and plasma gastrin responses (Kontureket al., 1994; Pu et al., 2004). Ethanol extract andwater extract ofAbrus cantoniensis, Saussurea lappa, Eugenia caryophyllata, Mag-nolia officinalis and Ligusticum species strongly inhibited thegrowth of Helicobacter pylori which is an important etiologicimpetus leading usually to chronic active gastritis and gastriculcer (Li et al., 2005).

5.9. Cardioprotective

A study on the edible plants common in Asian diets suchas Ipomoea batatas, P. betle, A. occidentale, Gynandropsis gynan-dra, C. papaya, and Mentha arvensis extracts showed that theyexhibitedmore than 50% relaxing effect on aortic ring prepara-tions. P. betle andC. citratus showed comparable vasorelaxationon isolated perfuse mesenteric artery preparation (Runnieet al., 2004). 14-Deoxy-11,12-didehydroandrographolide fromA. paniculata was shown to have bradycardia-inducing and-adrenoceptor antagonistic properties in vivo using anes-thetized Sprague-Dawley rats (Zhang et al., 1998). Theseeffects are brought in relation to potential health benefits.A cardioprotective effect of C. asiatica on the antioxidanttissue defence system during doxorubicin induced cardiacdamage in rats has been reported. Doxorubicin is a clinicallyused cytostatic agent that displays cardiotoxicity as a majorside effect. The aqueous extracts of this plant produced asignificant reduction in the levels of lactate dehydrogenase,creatine phosphokinase, glutamate oxaloacetate transami-nase and glutamate pyruvate transaminase. Increased activityin serum of these enzymes is a well-known diagnostic markerof myocardial function. The triterpenes (asiatic acid and asi-aticoside) may be responsible for the cardioprotective effectof C. asiatica extracts, because of their antooxidative effect(Gnanapragasam et al., 2004). The cardioprotection providedby ligustrazine (tetramethylpyrazine) is related to a reductionof TNF-alpha content by inhibition of free radical productionin isolated rats hearts. It was known that TNF-alpha can con-tribute to myocardial damage during ischaemia-reperfusion(Zhou et al., 2004). The studies of the antioxidative andcytoprotective effects using H9c2 cardiac myoblasts showedthat Phyllanthus urinaria have a protective activity againstdoxorubicin cardiotoxicity. This protection was mediatedthrough multiple pathways such as enhancement of sur-vival factor through elevation of glutathione, activation ofcatalase/superoxide dismutase activity and inhibition of lipidperoxidation. This plant may serve as an alternative sourceof antioxidants for prevention of doxorubicin cardiotoxicity(Chularojmontri et al., 2005).5.10. Antihypertensive

Ethanolic extracts of fresh matured fruits of C. papayamarkedly depressed the blood pressure and heart rate in ratsc ine 4 ( 2 0 1 4 ) 5173

with hypertension when compared with the normotensivecontrols. The extracts (20mg/kg i.v.) decreased the blood pres-sure by about 20.1%, 50.7% and 54.5% in normotensive, renaland DOCA-salt hypertensive rats, respectively. The extractappeared to be more potent then hydralazine (200g/kgi.v.), a well known antihypertensive (vasodilator) agent thatdecreased the blood pressure by about 10.7%, 22.8% and 26.4%in the three applied models of hypertension (Eno et al., 2000).The total triterpenoid fraction of C. asiatica, a venoactive drugacting on the microcirculation and on capillary permeability,has been tested in three groups of patientswith venous hyper-tension. The improvement of signs and symptoms observedin venous hypertensive patients taking the extracts corre-lated well with the improvement of the variation of capillaryfiltration rate (assessed by venous occlusion plethysmogra-phy) and ankle oedema (swelling sensation, restless lowerextremity, pain and cramps, tiredness (De Sanctis et al., 2001).The vasodilatory effect of plants from the Curcuma specieshave been studied. C. longa, for example, induced endothelium-independent vasodilatation. It was concluded that Curcumaherbs have hypotensive and protective effects on the endothe-lium in spontaneously hypertensive rats, and its mechanismis thought to be related to a radical scavenging effect andimprovement of hemorheology (Goto et al., 2005). A majorconstituent in the water decoction of Orthosiphon aristatusleaves, methylripariochromene A (a benzochromene), exhib-ited a continuous decrease in systolic blood pressure aftersubcutaneous administration in conscious stroke-prone spon-taneously hypertensive rats. The leaves of this plant known askumis kucing in Indonesia is commonly used by the Javanesepeople in their jamu, mainly for treatment of hypertension(Ohashi et al., 2000a,b).

5.11. Anti-asthma, antitussive and anti-allergic

A study of selected medicinal plants that are traditionallyused for asthma treatment in Indonesia indicated that alco-holic extracts from the leaves of Plantago major, the leavesand fruits of Eucalyptus globulus, Cinnamomum massoiae cor-tex and the leaves of Vitex trifolia plus two hexane extracts ofE. globulus leaves inhibited IgE-dependent histamine releasefrom RBL-2H3 cells suggesteding that these extracts con-tain active compounds which inhibit mast-cell degranulation,and thus may be used in the development of new drugsfor treating asthma and/or allergic disease (Ikawati et al.,2001). An ethanolic extract of A. scholaris leaves inducedpronounced bronchodilatory activity in anaesthetized ratsmediated presumably by prostaglandins (Channa et al., 2005).Clinical studies with A. paniculata extract showed effectiv-ity at the early treatment of uncomplicated acute upperrespiratory tract infection. In clinical studies, an ethanolicextract of A. paniculata alone or in combination with theethanolic extract of A. senticocus appeared to be more effec-tive than placebo in the treatment of an uncomplicatedacute upper respiratory tract infection (Poolsup et al., 2004).The active constituents of A. paniculata, andrographolide

and neoandrographolide, have been reported to have anantiallergic effect in a rat model. This effect is due to itsmast cell stabilizing activity, comparable to the antialler-gic drug, disodium cromoglycate. Neoandrographolide was


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ore potent than andrographolide in this study (Gupta et al.,998). An antitussive effect of liquiritin apioside, liquritinnd liquiritigenin, isolated from G. radix (licorice) has beeneported. The effect of liquiritin apioside may depend onoth peripheral (modulation of ATP-sensitive K+ channels)nd a central mechanism (modulation of serotonergic sys-em) (Kamei et al., 2005). An aqueous extract of A. galangahizomawas found to inhibit the release of-hexosaminidase,marker of antigen-IgE-mediated degranulation in RBL-2H3ells. The compounds, 1S-1-acetoxychavicol acetate and 1S--acetoxyeugenol acetate isolated from A. galanga inhibited-hexosaminidase and a passive coetaneous anaphylaxiseaction inmice and the antigen-IgE-mediated TNF-alpha andL-4 production, both of which participate in the late phase ofype I allergic reactions (Matsuda et al., 2003a,b).

.12. Immunostimulating

n immunostimulating effect has been reported from pule (A.cholaris) that is used in South-East Asia mainly as an anti-alarial and antidysentery agent. In BALB/c mice an aqueousxtract of A scholaris bark stimulated a non specific immuneesponse, restored the reduction of phagocytic action inducedy prednisolone and protected the animals from the oppor-unistic infection caused by E. coli (Iwo et al., 2000). Thisffect in BALB/c mice was also shown by curcumin isolatedrom C. longa in (Antony et al., 1999). A polysaccharide extractrom the rhizome of A. galanga rhizoma showed a markedtimulating effect on the reticulo-endothelial system (RES)nd increased the number of peritoneal exudate cells, andpleen cells of mice, which may relate to immunomodulatingffects (Bendjeddou et al., 2003). Immunomodulating effectsere also shown by a methanolic extract from A. paniculatand isolates andrographolide, 14-deoxyandrographolide and4-deoxy-11,12-didehydroandrographolide that enhanced theroliferation and interleukin-2 (IL-2) induction in humaneripheral blood lymphocytes (Kumar et al., 2004). Hexanend aqueous extract of C. papaya seeds and its bioac-ive fractions significantly enhanced the phytohemagglutininesponsiveness of lymphocytes and inhibited the classicalomplement-mediated hemolytic pathway, indicating a pos-ible immunostimulating effect (Mojica-Henshaw et al., 2003).

.13. Central nervous system (CNS) activity

he essential oil from the fruits of C. cyminum, tradition-lly used as a stimulant exhibited anticonvulsant activityn both pentylenetrazole- and maximal electroshock-inducedeizures in male NMRI mice (Sayyah et al., 2002). Antidepres-ant effects have also been recently reported for curcumin.t is suggested that this effect may be mediated by actionsn the central monoaminergic neurotransmitter systems (Xut al., 2005). G. radix, together with other medicinal plantsuch as Bulpleuri radix, Paeoniae radix and Angelicae sinen-is radix, have been tested in patients who were exhibitingremor, a possible symptom of antipsychotic-induced Parkin-

onism. The results concluded that the combination of theedicinal plantsmentionedwas effective against tremor fromarkinsonism (Ishikawa et al., 2000). Methanol leaf extract of. macrophylla has been reported to have a CNS depressantine 4 ( 2 0 1 4 ) 5173 67

activity. It caused a significant reduction in spontaneous activ-ity, a decrease in exploratory behavioural pattern, a reductionin muscle relaxant activity and also significantly potenti-ated phenobarbital sodium-induced sleeping time in mice(Chattopadhyay et al., 2004a,b).

5.14. Others

Various other activities have been reported from themedicinalplants which are used in jamu. Grosvenor et al. (1995) surveyedthe medicinal plants in Riau Province, Indonesia. Out of onehundred and fourteen species of flowering plants belongingto 51 families and claiming to have medicinal uses, 50% wererecorded to be used to combat fever, 33% for diarrhoea and 31%for other gastrointestinal problems.Unnyet al. (2003) reviewedabout 161 medicinal plants which are a potential source ofnew contraceptive principles. The review contains the isolatedcompounds and the mechanism of actions. Some of them areused in jamu, e.g. F. vulgare,Abrus precatorius,Muraya paniculata,Punica granatum,C. longa, andC. zedoria. They inhibited implan-tation and increased foetal loss inmice and reduced secretoryactivity and weight of accessory sex glands. Aqueous extractsof C. papaya andAnanas comosus have been reported to possessdiuretic activity. Both plant extracts gave similar profiles ofurinary electrolyte excretion to that of hydrochlorothiazide(thiazide diuretic). The analyses of the urinary osmolality andelectrolyte excretion per unit time, togetherwith the plant saltcontents, may help to differentiate the mechanism by whichthese plants act as diuretics The results indicated that thediuretic activity of A. comosus was intrinsic and not a resultof the salt loading effect, whereas C. papaya extracts may haveresulted from the high salt content of the extract. This activitycorrelated well with themaximum volume, the highest osmo-lality, and the amount of electrolytes excreted during urinecollection (Sripanidkulchai et al., 2001). A methanolic extractsof Areca catechu, Brucea sumatrana, Allamanda cathartica, col-lected in Sumateran rainforests showed strong antinematodalactivity against Bursaphelenchus xylophilus (Alen et al., 2000).

6. Known risks and side effects ofmedicinal plants used in jamu

It is generally assumed by the public, and also even bysome medical practitioners, that plant drugs are harmlessand therefore are preferable to orthodox medicines. Althoughon the whole plant medicines used at the correct dosageelicit fewer side effects than their orthodox counterpartstheir safety and efficacy cannot automatically be assured.Numerous examples on herb-induced side effects have beendocumented (Aronson, 2009).

Data from clinical trials suggest that the most commonlyexperienced adverse effects of Panax ginseng for exampleare headache, sleep and gastrointestinal disorder. Kava-kava (Piper methysticum), currently banned in many Europeancountries and in the USA may cause tiredness, low energy,

headache, hepatoxicity, skin reactions and gastrointestinalsymptoms. A 52-year-old woman for example, was seen withpapules and plaques on the face and later on her dorsal andventral thorax and arms after taking a kava product (type


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of extract unspecified) for 3 weeks (Stevinson et al., 2002).Although ginger (Zingiberis officinalle) shows a very broad rangeof pharmacological effects it may cause heartburn and act asa gastric irritant in doses exceeding 6g dried ginger. Inhala-tion of dust from ginger may produce IGE-mediated allergy(Chrubasik et al., 2005).

The risk of herbal medicines producing an adverse reac-tion depends not only on the medicine and its dosage butalso on consumer-related parameters, such as age, genet-ics, concomitant diseases and co-medication (herbherb andherbdrug interactions). Reports about herbal medicinal prod-ucts affected by contamination, adulteration or substitutionof botanical material have repeatedly caused concern. Asianherbal medicinal products including jamu are most oftenimplicated (Ernst and Pittler, 2002). A report by Limyati andJuniar (1998) mentions the microbial contamination of rawmaterial and end product of jamu gendong. Agranulocytosisand citrobacterial infection have been found after using jamucontaining deliberately admixed phenylbutazone (to enhancethe analgetic and anti-inflammatory effect) (Paul et al., 2005).A study of 23 commercial jamu products showed the presenceof natural aflatoxins that exhibit carcinogenic, teratogenic andmutagenic properties (Ali et al., 2005). A case report describesa 45-year-old patient who had highly elevated transami-nases and elevated lactate dehydrogenase after having usedM. citrifolia. This gave rise to the suspicion of herbal toxic-ity, which was confirmed by taking a liver biopsy from thepatient (Millonig et al., 2005). Finally, there is always the riskof herbdrug interactions, which may influence the effective-ness of conventional drugs (Naet al., 2011; Izzo andErnst, 2009;Kennedy and Seely, 2010; Tarirai et al., 2010) Users, prescribersand producers of jamu should be aware of this. Definitely,moreand continuous control is needed on traditional medicinessuch as jamu to guarantee safety for the user. This shouldpreferably be regulated onanational level and implemented inthe manufacturing process as well as later, when the productis on the market (Woerdenbag et al., 2012).

7. Conclusion

Jamu is and will remain an integral part of the Indone-sian healthcare system. The in vitro, in vivo and clinicalstudies on medicinal plants that are used in jamu havein part scientifically proved their claimed biological activi-ties. Species belonging to the family Zingiberaceae such asCurcuma, Zingiber, Kaempferia, are the most frequently usedplants in jamu. These species have also been studied inten-sively for their secondary metabolites and biological activity.Curcumin and panduratin are typical examples of bioactivesecondary metabolites from these plant species. As mem-bers of the Zingiberaceae are generally regarded as safe forhuman consumption, these species are excellent candidatesfor development as novel standardized jamu products. BPOMhas carried out systematic and comprehensive research onnine priority plants used in jamu in Indonesia, i.e. ginger

(Z. officinale) and king of bitter (A

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