Untitled Document

Effects of Eurycoma longifolia jack on laevator ani muscle in both uncastrated and
testosterone-stimulated castrated intact male rats.

Ang HH, Cheang HS.

School of Pharmaceutical Sciences, University Science Malaysia, Minden, 11800, Penang, Malaysia. hhang@usm.my

It has been reported that Eurycoma longifolia Jack commonly known as Tongkat Ali has gained notoreity as a symbol of man's ego
and strength by the Malaysian men because it increases male virility and sexual prowess during sexual activities. As such, the effects of
200, 400 and 800 mg/kg of butanol, methanol, water and chloroform fractions of E. longifolia Jack were studied on the laevator ani
muscle in both uncastrated and testosterone-stimulated castrated intact male rats after dosing them for 12 consecutive weeks. Results
showed that 800 mg/kg of butanol, methanol, water and chloroform fractions of E. longifolia Jack significantly increased (p<0.05) the
leavator ani muscle to 58.56+/-1.22, 58.23+/-0.31, 60.21 +/-0.86 and 62.35 +/-0.98 mg/100 g body weight, respectively, when
compared with the control (untreated) in the uncastrated intact male rats and 49.23+/-0.82, 52.23+/-0.36, 50.21+/-0.66 and
52.35+/-0.58 mg/100 g body weight, respectively, when compared to control (untreated) in the testosterone-stimulated castrated
intact male rats. Hence, the pro-androgenic effect as shown by this study further supported the traditional use of this plant as an
aphrodisiac.

In vitro anti-tumor promoting and anti-parasitic activities of the quassinoids from Eurycoma longifolia,
a medicinal plant in Southeast Asia.

Jiwajinda S, Santisopasri V, Murakami A, Kawanaka M, Kawanaka H, Gasquet M, Eilas R, Balansard G, Ohigashi H.

Central Laboratory and Greenhouse Complex, Kasetsart University, Kamphaeng Saen Campus, Nakhon Pathom 73140, Thailand.
rdiswj@nontri.ku.ac.th

Some quassinoids (1-6) isolated previously as plant growth inhibitors from the leaves of Eurycoma longifolia Jack. (Simaroubaceae)
were subjected to in vitro tests on anti-tumor promoting, antischistosomal and plasmodicidal activities. The most active compound for
inhibition of tumor promoter-induced Epstein-Barr virus activation (anti-tumor promotion) was 14,15beta-dihydroxyklaineanone (5,
IC(50) = 5 microM). Longilactone (1) gave significant antischistosomal effect at a concentration of 200 microg/ml.
11-Dehydroklaineanone (3) and 15beta-O-acetyl-14-hydroxyklaineanone (6) showed potent plasmodicidal activity (IC(50) = 2
microg/ml). Thus it was suggested that E. longifolia possesses high medicinal values due to the occurrence of a variety of quassinoids.
Copyright 2002 Elsevier Science Ireland Ltd.

Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia
Jack.

Ang HH, Ngai TH.

School of Pharmaceutical Sciences, University of Science Malaysia, Minden, 11800, Penang, Malaysia.

The aphrodisiac effect of Eurycoma longifolia Jack (0.5 g/kg) was evaluated in noncopulator male rats using an electrical cage.
Fractions of E. longifolia Jack decreased the hesitation time of noncopulator male rats, throughout the investigation period.
Furthermore, it possessed a transient increase in the percentage of the male rats responding to the right choice, more than 50% of the
male rats scored "right choice" after 3 weeks post-treatment and the effect became more prominent after 8 weeks post-treatment (only
40-50% of the control male rats responded to the right choice) using the electrical copulation cage. Hence, this study lends further
support to the use of the plant by indigenous populations as a traditional medicine for its aphrodisiac property.

Evaluation of the potency activity of aphrodisiac in Eurycoma longifolia Jack.

Ang HH, Ikeda S, Gan EK.

School of Pharmaceutical Sciences, University Science Malaysia, Minden, 11800, Penang, Malaysia. hhang@usm.my

The butanol, methanol, water and chloroform extracts of the roots of Eurycoma longifolia Jack were studied using various tests of
potency of treated male rats. The results showed that E. longifolia produced a dose-dependent, recurrent and significant increase in the
episodes of penile reflexes as evidenced by increases in quick flips, long flips and erections of the treated male rats during the 30 min
observation period. These results provide further evidence that E. longifolia increases the aphrodisiac potency activity in treated
animals. Copyright 2001 John Wiley & Sons, Ltd.

Effects of Eurycoma longifolia Jack (Tongkat Ali) on the initiation of sexual performance of
inexperienced castrated male rats.

Ang HH, Cheang HS, Yusof AP.

School of Pharmaceutical Sciences, University Science Malaysia, Penang, Malaysia.

We studied the effects of Eurycoma longifolia Jack, commonly known as Tongkat Ali in Malaysia, on the initiation of sexual
performance and the weights of sexual accessories in inexperienced castrated male rats. The doses of 200, 400 and 800 mg/kg body
weight, which were extracted from E. longifolia Jack, were orally administered to the rats twice daily for 10 days prior to the tests and
continued throughout the test period. Testosterone was used as a positive control after injecting 15 mg/kg daily subcutaneously for 32
days. Results showed that E. longifolia Jack produced a dose-dependent increase in sexual performance of the treated animals, but the
E. longifolia Jack groups showed lower sexual performance in mounting, intromission and ejaculation than the testosterone group.
Further results also showed that E. longifolia Jack promoted the growth of both ventral prostate and seminal vesicles as compared with
the control, but the growth of sexual accessories at 800 mg/kg of butanol, methanol, water and chloroform fractions of E. longifolia
Jack was less than that of testosterone treated group. The present study therefore gives further evidence of the folkuse of E. longifolia
as an aphrodisiac.

In vitro anti-tumor promoting and anti-parasitic activities of the quassinoids from Eurycoma longifolia,
a medicinal plant in Southeast Asia.

Jiwajinda S, Santisopasri V, Murakami A, Kawanaka M, Kawanaka H, Gasquet M, Eilas R, Balansard G, Ohigashi H.

Central Laboratory and Greenhouse Complex, Kasetsart University, Kamphaeng Saen Campus, Nakhon Pathom 73140, Thailand.
rdiswj@nontri.ku.ac.th

Cytotoxic and antimalarial constituents of the roots of Eurycoma longifolia.

Kardono LB, Angerhofer CK, Tsauri S, Padmawinata K, Pezzuto JM, Kinghorn AD.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60612.

By bioactivity-directed fractionation, five cytotoxic constituents have been characterized from the roots of Eurycoma longifolia
collected in Kalimantan, Indonesia. Four canthin-6-one alkaloids, namely, 9-methoxycanthin-6-one,
9-methoxycanthin-6-one-N-oxide, 9-hydroxycanthin-6-one, and 9-hydroxycanthin-6-one-N-oxide, and one quassinoid,
eurycomanone, were found to be cytotoxic principles. Each of these compounds was evaluated against a panel of cell lines comprising
a number of human cancer cell types [breast, colon, fibrosarcoma, lung, melanoma, KB, and KB-V1 (a multi-drug resistant cell line
derived from KB)] and murine lymphocytic leukemia (P-388). The canthin-6-ones 1-4 were found to be active with all cell lines tested
except for the KB-V1 cell line. Eurycomanone was inactive against murine lymphocytic leukemia (P-388) but was significantly active
against the human cell lines tested. Two additional isolates, the beta-carboline alkaloids beta-carboline-1-propionic acid and
7-methoxy-beta-carboline-1-propionic acid, were not significantly active with these cultured cells. However, compounds 5 and 7 were
found to demonstrate significant antimalarial activity as judged by studies conducted with cultured Plasmodium falciparum strains. The
structures of the novel compounds 2-4 and 7 were established by spectral and chemical methods.

In vitro antimalarial activity of quassinoids from Eurycoma longifolia against Malaysian
chloroquine-resistant Plasmodium falciparum isolates.

Ang HH, Chan KL, Mak JW.

Three quassinoids from the roots of Eurycoma longifolia Jack were evaluated for antimalarial activity against nine Plasmodium
falciparum isolates obtained from patients infected with chloroquine-resistant malaria. The results indicated that eurycomanol,
eurycomanol 2-O-beta-D-glucopyranoside, and 13 beta, 18-dihydroeurycomanol possessed antimalarial activity with IC50 values of
1.231-4.899 microM, 0.389-3.498 microM, and 0.504-2.343 microM, respectively, compared with 0.323-0.774 microM for
chloroquine.

Studies on the anxiolytic activity of Eurycoma longifolia Jack roots in mice.

Ang HH, Cheang HS.

School of Pharmaceutical Sciences, University Science Malaysia, Minden, Penang.

The anxiolytic effect of Eurycoma longifolia Jack in mice was examined. Fractions of E. longifolia Jack extract produced a significant
increase in the number of squares crossed (controls= 118.2 +/- 10.2 squares), but significantly decreased both the immobility (controls
= 39.4+/- 4.0 sec) and fecal pellets (controls= 12.3 +/-2.1 fecal pellets) when compared with control mice in the open-field test; they
significantly increased the number of entries (controls=6.7+/-0.5 entries) and time spent (controls=42.9+/-0.1 sec) in the open arms,
but decreased both the number of entries (controls= 13.2+/-0.7 entries) and time spent (controls= 193.4+/-0.7 sec) when compared
with the control mice in the closed arms of the elevated plus-maze test. Furthermore, fractions of E. longifolia Jack extract decreased
the fighting episodes significantly (controls= 18.0+/-0.4 fighting episodes) when compared with control mice. In addition, these results
were found to be consistent with anxiolytic effect produced by diazepam. Hence, this study supports the medicinal use of this plant for
anxiety therapy.

Effect of 7-day daily replacement of culture medium containing Eurycoma longifolia Jack constituents
on the Malaysian Plasmodium falciparum isolates.

Ang HH, Chan KL, Mak JW.

School of Pharmaceutical Sciences, University Science Malaysia, Penang.

Six Malaysian chloroquine-resistant Plasmodium falciparum isolates were cultured in vitro following the candle-jar method. Antimalarial
evaluations of daily replacement of culture medium containing chloroquine and a semi-purified extract of Eurycoma longifolia Jack
(containing 13 beta, 18-dihydroeurycomanol (1), eurycomanol-2-O-beta-D-glucopyranoside (2), eurycomanol (3) and eurycomanone
(4)) were performed on 6-well plates at 37 degrees C for a week. Presence or absence of the parasites was determined
microscopically on thin-film Giemsa-stained preparations. Results showed that the antimalarial activity of Eurycoma longifolia Jack was
dose-dependent and reached a maximum of < 50% at 0.07-5.00 micrograms ml-1 after 1 day post-treatment. However, complete
inhibitions were observed at 1.25-5.00 micrograms ml-1 extract after 3 days post-treatment and 0.62 and 0.31 micrograms ml-1 after
4 and 6 days post-treatment, respectively. Further results indicated that chloroquine exhibited total inhibition at concentrations > 2.50
and 0.62 micrograms ml-1 after 1 and 2 days post-treatment, respectively and at all concentrations after 3 days post-treatment.

Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia
Jack.

Ang HH, Ngai TH.

School of Pharmaceutical Sciences, University of Science Malaysia, Minden, 11800, Penang, Malaysia.

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Eurycoma Longifolia Jack_ (Pasak Bumi)

Description
Eurycoma longifolia (Simaroubaceae) is a small tree to 15 m high. Plants dioecious (flowers on a
plant are either male or female). Leaves compound, long, and crowded at the tips of the
branches. When the leaves fall they leave large scars on the stems. Leaflets are
ovate-lanceolate, sessile or nearly so, and opposite. Flowers are borne in axillaries panicles,
mostly large and lax, and puberulous with short hairs. Flowers are unisexual; male flower has
sterile pistil, female flower has sterile stamens. Fruits ellipsoid or ovoid, 10-20 x 5-12 mm, green
to blackish-red when ripe.

Ecology
E. longifolia prefers acid and sandy soils at low altitude up to 700 m above sea level. Plants
usually grow in beach forests, primary and secondary forests, mixed dipterocarp forests and
also in heath forests. In Riau Province, Sumatra, 1991, the author found that plants were
growing in areas with an average temperature of 25C and 86% humidity. The soils in this area
were found to be poor in nutrients, but mycorrhizal fungi were found growing near the plants
and may indicate an association. Seedlings require shade, during which time they develop an
extensive root system. Following juvenile stages, plants need stronger light to develop
vegetative and reproductive parts. E. longifolia flowers and fruits throughout the year, with
peak flowering from June-July and peak fruiting in September.

Distribution
E. longifolia originates from South East Asia, including Indonesia, Malay Peninsula, Thailand,
Laos, Cambodia and Vietnam. In Indonesia, this species only occurs naturally in Sumatra and
Kalimantan.

Uses
Though E. longifolia is currently mostly known as an aphrodisiac, in South East Asia, all parts
of E. longifolia plants have long been used medicinally. The plant is commonly used throughout
the region as a tonic after childbirth. The bark of the roots is used in the Malay Peninsula to
cure fever, ulcers in the mouth, and intestinal worms. The Malays also use the paste of the plant
to relieve headache, stomachache, pain caused by syphilis, and many other general pains. In
parts of Sumatra and Kalimantan, the root is used as an anit-pyretic. In Lampung and Belitung it
is used as a medicine for dysentery. The people of Sabah and Kalimantan make a decoction of
the bark that is drunk to relieve pain in the bones or applied for washing itches. In Vietnam,
people use the flowers and fruits as a medicine for treating dysentery. In Riau, where the author
carried out research, people living in the surrounding forests boil the root or stem to cure
malaria. One of the most unique uses for E. longifolia is that of the Sakai ethnic group in
Sumatra who use the plant as an amulet to protect people from the smallpox virus.

Phytochemistry
The active constituents in E. longifolia, and many other species in the Family Simaroubaceae,
include quassin, neo-quassin, glaukarubin, sedrin, eurycomanol that are mostly derivatives from
compounds with 20 carbon atoms.

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Giving a Boost to the Healing System

Local herbs are the best for us. They have gorwn with us. They were put there by Nature for us.
all over Nature, we see tonic type herbs that concentrate their power in the roots. The most
famous is Chinese ginseng.

However, there are other ginseng-tpe herbs all over thew orld. Amoung these are American
ginseng, Siberian ginseng and, to a lesser extent, Indian ginseng. Such ginseng type herbs are
also ound in South America as well.

We have our own ginseng too - Eurycoma longifolia, which is commonly known in Malaysia as
Tongkat Ali. Roughly translated, its Ali's walking stick. The name is an obvious reference to the
plant's long tradition of use as an aphrodisiac and a tonic for men.

A member of the Simaroubaceae family, it is found throughout Malyasia, Borneo and Sumatra.
Traditionally, Tongkat Ali's long woody tap root is used by decoction. It has an intensely bitter
taste (a standard feature fo root-borne tonics) and has been used to treat fevers and, most
suprisingly, malaria.

MALAYSIAN GINSENG

In order ot understand Tongkat Ali as a Malaysian ginseng, let us look at how herbs are
classified in Chinese traditional medicine. Chinese physicians tend to classify them into three
major categories - superior, middle and inferior. Inferior drugs or herbs are those with specific
effects in specific conditions. These are the so-called magic bullets, modern medicine's highest
therapeutic ideal.

Middle drugs have broader prowers because they tend to strengthen body conditions. Superior
drugs are tonics because they work for everything.

In the Chinese concept, superior drugs work by stimulating the defensive action of the body,
making it more resistant to assults of all kinds. These drugs are not toxic. They are not weapons
against specific diseases. Yet, bu increasing the body's resistance, they can cure a wide range
of maladies.

APHRODISIAC?

Mere mention of Tongkat Ali, though, usually provokes funny looks, cheeky smiles or very
naughty laughs. Its reputation as an aphrodisiac seems to be very deeply entrenched in the
Malaysian psyche. While this has ineed been proven to be true, Tongkat Ali is actually much
more than that.

Ginseng also has the reputation of being an aphrodisiac in the early days. Chinese Emperors
used to richly reward those who could provide them pure ginseng root that was reputed to
enhance their sexual prowess.

However, veyr proper marketing and selective R&D efforts have made ginseng better known as
the tonic that it is. A similar scenario could work for Tongkat Ali.

RESEARCH

Sadly, little research has been done on Tongkat Ali when coompared to ginseng-type
compounds from Korea, China, Siberia, or even the Americas. It has been the subject of some
phytochemical research for teh past 20 years however.

It has been found to contain quassinoids such as eurycomanol and eurycomanolactone,
alkaloids, sterols, sapenins and terpenoids. Much of the research has been focused on the
plant's quassinoid constituents. This togetherw ith several other related species, have been the
focus of research for their anti-tumour and anti-cancer properties.

In Malaysia, researhc has confirmed that isolated constituents as well as whole plant extract
show aphrodisiac, anti-malarial, febrifuge, antihistaminic, anti-tumour, anti-ulcer and antiviral
activity. Tongkat Ali would thus help improve both physical and mental performance. It could
also be used to treat fatigue and exhaustion. It would them make it a superior drug by traditional
Chinese definition.

Tongkat Ali could be classified as a tonic. Tonics are natural products that increase the
efficiency of the healing system and help it neutralise harmful influences. In fact, the word tonic
is derived from the Greek word meaning stretch. Tonics stretch or tone the system in the same
way physcial exercise tones muscles.

Tongkat Ali could also be an adaptogen that enables the body to resond to stress as a whole.
A smallpox vaccine would strengthen the body against that particular virus, or the anti-malarial
medicine would protect against malaria.

However, an adaptogen would help the body respond to a wide spectrum of stressors - sleep
deprivation, heat, cold, stress, trauma, infection, and even radiation!

As mentioned earlier, these results reflect characteristic adaptogenic properties that are also
found in Chiensea nd Siberian Ginseng.

Its possible mechanism of aciton is similar to that of other classic tonic herbs that possess
triterpenoid saponins (of which the quassinoids are a degradation product) through possible
interaction with hormonal receptor sites. Taken in the right dose and frequency, there would be
no side effects.

HOT AND COLD

All ginseng-like compounds are generally safe if used in moderate doses. However, certain
types of ginseng are classified as hot or heaty. They could raise blood pressure in some
individualsand also irritate and upset the hormonal balance.

This again goes back to the climate and environment that the ginseng is gorwn. As an
adaptogenic, ginseng accordingly helps the individual cope with phsycial stresses caused by
weather.

Thus, ginseng from cold climates tends to be hot. It was meant for people living there. In the
cold climate, it serves to warm the person taking it. That is why certain Chiense and Korean
ginsengs are considered heaty.

Ginseng that grows in more moderate climates would be cooler. Thus, our Tongkat Ali woudl be
ideal for us who live and work in this climate. This is another powerful argument for local herbs
being best for us.

PRECIOUS

Tongkat Ali is certainly highly priced by traditional kampung folk. It is especially valued by the
elderly because it can imporve appetite and digestion, tone skin and muscle, improve immune
funciton, and restore depleted sexual energy. Folklore has it that men say it is not for women
simply because they do not want to share its limited supply.

In one of my herbal excursions deep into the rain forest, one orang asli shaman advised me not
to waste tongkat ali in my youth. Save it for your old age, he said, then you will see what it can
do for you.

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Malaysian root effective against cancers

One of the most astonishing herbal medications known to us is found
in Southeast Asia. In Malaysia, the plant from which it is derived is
called "tongkat ali"; in Indonesia, its name is "pasak bumi; the
scientific name is "eurycoma longifolia jack".

The plant is also used in Thailand, Cambodia, and Vietnam. However,
the most popular it is in Malaysia where its prime application is for
sexual enhancement.

Numerous scientific trials have proven that tongkat ali effectively rises testosterone levels, most
probably by interfering with the negative feedback action of androgens and estrogens on the
hypothalamus and pituitary glands, which, as last instance, control how much sex hormones are
produced in either sex.

Testosterone, best known for its power to enhance libido, of course, has many other benefits.
Sufficient supply will assure a general sense of well-being, and helps in the development of
intelligence.

Tongkat ali (pasak bumi, eurycoma longifolia) does even more: it's a proven treatment and
prophylacticum against malaria, reduces blood pressure, aids liver and kidney function, and much more.
Body builders effectively use it to stimulate muscle growth.

In Vietnam, the root is known as the herbal that cures 1000 diseases.

If the latest positive research results are confirmed, you can make this 1001. Research scientists of
the Massachusets Institute of Technology have been looking into the use of tongkat ali (eurycoma
longifolia) in the treatment of various cancers, and it seems that the herbal has a surprising potential
in this area. Here is what Reuters had to report on July 23, 2002 (as printed in the Straits Times of
Singapore):

Tongkat ali offers anti-HIV, anti-cancer hope

KUALA LUMPUR - A Malaysian jungle plant believed widely to be an aphrodisiac could also be effective
against cancer and the human immunodeficiency virus (HIV), a newspaper reported on Sunday.

The New Sunday Times said early results from a study by a Malaysian government-sponsored agency
and the Massachusetts Institute of Technology found that some chemical constituents of the tongkat
ali plant show high anti-cancer and anti-HIV activity.

HIV is the virus which causes Aids.

Mr Abdul Razak Mohamad Ali, director-general of the national Forest Research Institute Malaysia, was
quoted by the newspaper as saying that initial laboratory work had shown that the plant's chemical
constituents could be more effective than existing anti-cancer drugs.

Tongkat ali is said to boost the male sex drive, although Malaysian villagers have long used it to
improve blood circulation and cure skin diseases.

Reuters

Penis enlargement pills

A herbal supplement aimed at increasing penis size has become extremely popular over the last few months
and is now heavily promoted on many Internet lifestyle and sexual health sites. The name of the supplement
is InVigrex and it contains concentrates of a large number of sexuality-enhancing herbs, as well as the
erection amino acid arginine and minerals such as zinc which have been proven to support sexual function.
While I have ample prove that penis enlargement programs such as the one offered at MensPride.net can
increase the size of a man's organ by several inches, the claim is that regular consumption of InVigrex will
have the same effect without exercise (which, I admit, can be time-consuming). See the InVigrex website for
more information.

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Malaysia MIT Research Programmes

Project Title:
Quantitative measurement of the chemical or bioactive
constituents of Eurycoma longifolia (Tongkat Ali) and
development of standardized commercial Tongkat Ali
formulations as herbal remedies

Malaysia MIT

Research Background

Eurycoma longifolia (Tongkat Ali) is grown wildly in the
jungle slopes of Malaysia and is popularly sought after
singly or as an essential component in herbal remedies for a
variety of illnesses and as health supplements. Extracts of E.
longifolia roots have been reported to possess antimalarial,
antiulcer, antipyretic, cytotoxic, and aphrodisiac properties.

The yield of the bioactive constituents is extremely low at
less than 0.005%. Hence, they are not easily available for
further studies and for commercial preparations. The plant
also requires a longer time to produce the secondary
bioactive metabolites and their biological activities may be
derived from more than one of the constituents. It is
therefore more feasible to study and formulate a partial
purified standardized extract of the plant for medicinal uses.
At present, none of the commercial preparations of Tongkat
Ali has been standardized. The uniformity of quality of the
commercial preparations is questionable as often the age,
conditions of growth, and plant sources will undoubtedly
affect the concentration of the bioactive constituents.

This project focuses on using chemical, biochemical and
bioinformatic tools for standardizing extraction and
preparation of Tongkat Ali products with respect to
biologically active components.

Objectives

To identify the bioactive components of Eurycoma
longifolia for use as reference standards
To develop a sensitive method for measuring
chemical constituents of E. longifolia and
standardizing extracts for commercial use
To develop robust biological assays for monitoring
bioactivity in Tongkat Ali extracts
To conduct preclinical analysis of safety and
pharmacology of Tongkat Ali preparations

Research Activities

Identification and characterization of reference
standards
Development of chemical assays
Development of biological assays for selected
disease states
Identification of bioactive components
Development of standardization methods
Optimization of extraction conditions
Study mechanism(s) of action of bioactive
components
Development and application of robust
assay/screening systems for herbal extract potency
Preclinical analysis of safety and pharmacology
Development of E. longifolia products
Clinical trials

Key Researchers

Dr. Azizol Abdul Kadir (FRIM)
Dr. Ng Lean Teik (FRIM)
Prof. Dr. Chan Kit Lam (USM)
Dr. Zhari Ismail (USM)
Prof. Dr. Azimahtol Hawariah Lope Pihie (UKM)
Dr. Zakiah Ismail (IMR)
Dr. Johari Mohd Saad (UM)
Dr. Puziah Hashim (SIRIM)

Eurycoma longifolia, a potential
source for new compounds.
Participating Institutions

Forest Research Institute Malaysia (FRIM)
Universiti Science Malaysia (USM)
Universiti Kebangsaan Malaysia (UKM)
Universiti Malaya (UM)
Institute for Medical Research (IMR)
Standards and Industrial Research Institute of
Malaysia (SIRIM)

Intellectual Goals

Development of new assay methods for bioscreening
and standardization of nutraceuticals and herbal
extracts
Development of advanced analytical technologies for
isolation and characterization of secondary bioactive
metabolities
Chip technology for characterizing biological systems
Establishment of industry standards for quality and
potency of herbal medicines and guidelines for
manufacturing of herbal products.
Development of software for data mining, pattern
recognition and data analysis

MIT Research

Extracts of Eurycoma longifolia (Tongkat Ali) are
commonly used as a traditional medicine. It is generally
accepted that E. longifolia possesses various bioactive
compounds. Some compounds from E. longifolia are
suspected aphrodisiacs. E. longifolia has been used as an
ad hoc prescription drug but the drug lacks standardization.
Standardization establishes identity, and activity. In the case
of the aphrodisiac, standardization establishes the nature of
the active compound.

The overall objectives of this project are to develop
analytical methods to establish the chemical profile, to
standardize the Tonkat Ali formulation (fingerprinting) and
to identify the possible bioactive ingredients of E.
longifolia.

We are developing a HPLC procedure to be used as a
profile assay for aqueous extracts of E. longifolia.
Furthermore we are isolating and characterizing marker
compounds that are suspected to be related to the bioactive
properties of Tongkat Ali.

MIT Researchers

Professor ChoKyun Rha
Dr. T. G. Sambandan
Dr. JoonHo Choi
Dr. Se-Kyung Oh
Dr. In-Ho Kim
Dr. Mike Cardone
Ms. Puriwana Pradipasena
Ms. Senna Kim

Project Title:
In vitro propagation of Eurycoma longifolia via formation
of somatic embryogenesis

Research Background
Eurycoma longifolia (Tongkat Ali) is a single-stemmed
slow growing tree of the rainforests of Southeast Asia. It is
used throughout the region as herbal medicine and tonic.
The chemical ingredients have been chemically profiled;
hence it is possible to chemically screen plants for
genotypes of high quality. The active ingredients are
concentrated in tap root. The plant takes five years or more
to reach reproductive age, and usually the fruit is low, hence
the rates of seed production cannot sustain the existing level
of demand for this plant material.

Collection of this plant in forests has become very difficult
and non-economical. Commercial cultivation cannot
proceed because there is no guaranteed source of high
quality planting materials. Vegetative propagation
techniques usually result in the production of fibrous roots.
In vitro propagation technique, vis-à-vis somatic
embryogenesis is an attractive alternative as it is known to
produce tap roots. The use of somatic embryogenesis
technology for production of E. longifolia plantlets with the
emphasis in maintaining their tap root bioactive chemical
profile is being investigated.

Objectives

To assess the genetic diversity of natural and
domesticated populations of E. longifolia utilizing
molecular approaches
To develop plant regeneration techniques for E.
longifolia through in vitro production of somatic
embryos
To identify and select highly regenerable accession of
E. longifolia through molecular approaches
To develop feasibility studies of bioreactor
technology for the production of somatic embryos

Eurycoma longifolia, a traditional
medicinal plant.
Research Activities

Identification and sampling of E. longifolia for
nucleic acid extraction and in vitro propagation from
natural and domesticated populations
Optimization of protocols and extraction of high
quality DNA
AFLP analysis
Computation of genetic diversity parameters
Identification of suitable explants and optimization of
sterilization protocols for these explants
Optimization of media for callus induction
Optimization of media for maintenance or
multiplication of the embryogenic callus
Optimization of media for development, germination
and bulk-up of cultures of somatic embryos
Examination of different stages in somatic
embryogenesis of E. longifolia through histological
studies and SEM
Development of acclimatization and nursery
establishment
Selection and molecular investigation of E. longifolia
accessions
Identification and isolation of genes associated with
high regenerability
Feasibility studies of bioreactor for in vitro
production of somatic embryos
Feasibility studies of bioreactor technology for cell
culture for the production of secondary metabolites

Key Malaysian Researchers

Ms. Aziah Mohd Yusoff (FRIM)
Dr. Norwati Muhammad (FRIM)
Prof. Marziah Mahmood (UPM)
Dr. Kodi Isparan Kandasamy (TropBio Sdn Bhd)
Dr. Jenni Harikrishna (TropBio Sdn Bhd)

Participating Malaysian Institutions

Forest Research Institute Malaysia (FRIM)
Universiti Putra Malaysia (UPM)
TropBio Sdn Bhd

Intellectual Goals

Assessment of genetic diversity of E. longifolia
Formulation of media and determination of the
environmental parameters for the development of
plantlets via direct or indirect somatic embryogenesis
Scale up production of somatic embryos using
robotic technology
Development of genetic fingerprinting tools to
characterize highly regenerable accessions
Pattern recognition technology/software for genetic
fingerprinting of highly regenerable accessions
Determination of conditions for the development of
cell culture systems for secondary metabolite
production
Images of Interest

MIT Research

Our objective in Natural Product Discovery sub-project
1.1 is to establish the foundation for genetic fingerprinting of
Eurycoma longifolia accessions. Genetic fingerprints,
which are profiles of many genetic markers, can be used to
distinguish different plant materials (i.e. samples of E.
longifoliafrom different sources or samples with different
properties). Once a sufficiently large set of genetic markers
has been developed for this species, and once a diverse
enough sample of E. longifolia accessions have been
tested for a given property, it should be possible to
correlate the presence of certain markers with these
properties. Thus, it may be possible to identify sets of
genetic markers, or "fingerprints," which correlate with high
regenerability or with high yield of bioactive metabolites. In
this way, genetic fingerprints could be used to promote the
goals of E. longifolia micropropagation and the
standardization of materials used in nutraceutical
preparations.

Toward genetic fingerprinting tools for E. longifolia, we
have been developing methods for identifying and screening
single nucleotide polymorphisms within the E. longifolia
genome. We are adapting to use in plants a suite of
methods that have recently been described for use with
mouse and human genomes. Our work is proceeding via the
testing of these techniques in more easily studied plant
systems, such as Arabidopsis, and then onto E. longifolia
itself.

MIT Researchers

Professor ChoKyun Rha
Dr. Philip Lessard
Dr. Andrea Loos
Dr. Christopher Coldren
Dr. JoonHo Choi

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MIT research helps ID tree that ‘cures 1,000 diseases’

APRIL 3, 2003
Contact

Tongkat Ali

Asiah binti
Osman
Philip A. Lessard

Genetic tools developed by MIT and Malaysian researchers will help identify and preserve a Southeast Asian tree containing a
substance that inhibits viruses and boosts fertility. The work is reported in the March 2003 issue of Plant Physiology.

Compounds extracted from the roots of the tree may lead to useful new drugs. New genetic tools for studying the trees and
other tropical plants were developed by researchers at MIT and the Forest Research Institute of Malaysia (FRIM).

Working under the Malaysia-MIT Biotechnology Partnership Program supported by the Ministry of Science, Technology and
the Environment of Malaysia, the researchers created a technique that genetically fingerprints a tree known in Malaysia as
Tongkat Ali.

Root extracts of Tongkat Ali are used widely in Southeast Asia as a dietary supplement for treating a variety of ailments. The
Vietnamese name of the tree indicates that it “cures 1,000 diseases.” The extracts have reported aphrodisiac properties and
have been shown to boost fertility in laboratory animals.

To preserve and eventually engineer useful traits in medicinal plants and maintain genetic diversity, as well as to identify
medicinal plants, the research teams developed genetic tools known as single nucleotide polymorphisms, or SNPs (pronounced
“snips”).

SNPs are small changes in the genetic makeup of individual plants. By taking snapshots of which plants possess which SNPs,
researchers are able to distinguish plants from very different genetic backgrounds. This allows researchers to maintain
populations of plants that represent as much genetic diversity as possible.

Researchers also can determine whether individual SNPs in a plant can predict whether chemical components of that plant will
have particularly potent medicinal properties. This information will be useful for breeding plants that can then be used to
manufacture nutritional supplements and pharmaceuticals derived from Tongkat Ali.

Asiah binti Osman, a FRIM research scientist working in the lab of MIT Professor of Biology David E. Housman, and research
scientist Philip A. Lessard in Professor of Biology Anthony J. Sinskey’s lab developed the SNP technology.

“The SNPs will be used to survey natural populations of Tongkat Ali, allowing us to identify the best possible plant material,”
Lessard said. “This plant material will then be used to establish biotechnology manufacturing operations and supply raw material
for extracting medicinal compounds.”

The Malaysia-MIT Biotechnology Partnership Program, directed at MIT by ChoKyun Rha, professor of biomaterials science
and engineering, is a multiyear collaboration aimed at developing the biotechnology industry in Malaysia.

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New potential herbal medication against ovarian cancer

One of the most astonishing herbal medications known to us is found in Southeast Asia. In Malaysia,
the plant from which it is derived is called "tongkat ali"; in Indonesia, its name is "pasak bumi; the
scientific name is "eurycoma longifolia jack".

The plant is also used in Thailand, Cambodia, and Vietnam. However, the most popular it is in Malaysia
where its prime application is for sexual enhancement.

Tongkat ali (pasak bumi, eurycoma longifolia) does much more: it’s a proven treatment and
prophylactic against malaria, reduces blood pressure, aids liver and kidney function, and much more.
Body builders effectively use it to stimulate muscle growth.

In Vietnam, the root is known as the herbal that cures 1000 diseases.

Now, research scientists of the Massachusetts Institute of Technology have found out that tongkat ali
(eurycoma longifolia) has great potential in the treatment of some cancers, especially ovarian cancer.
The following article from http://www.cancernetwork.com/ had been posted on July 29 on
http://www.acor.org/ with the complete URL
http://listserv.acor.org/SCRIPTS/WA-ACOR.EXE?A2=ind0207E&L=ovarian&P=R516

Malaysian Plant Harbors Oncologic Compound

According to The New Sunday Times of Malaysia, scientists at the Massachusetts Institute of
Technology and from the Malaysian government have found that ingredients of the "tongkat ali" plant
have strong activity against cancer and HIV infection. In particular, the substance may be active
against cancer of the ovary.

Tongkat ali, or Eurycoma longifolia, usually is used as a general medicinal tonic; it has been useful after
childbirth and to treat hypertension, fever, tuberculosis, fever, diarrhea, jaundice, and dysentery.
However, it also has achieved fame throughout the country for its supposed aphrodisiac properties.

According to Dr. Abdul Razak Mohd Ali, director general of the Forest Research Institute Malaysia,
initial laboratory testing showed that various chemical constituents of the plant could be more
effective than existing chemotherapy, especially when ovarian cancer is considered. He noted that the
government and MIT have signed an agreement covering all parts of the research. In addition, the
parties agreed to share in benefits resulting from possible commercialization of any discoveries.

One problem noted is that some Malaysians have harvested the plant from jungles throughout the
country. In recent years, 10 times the amount of plant has been taken from the natural surroundings,
leaving certain forests of Kedah and Langkawi without the plant. The Forest Research Institute
Malaysia is encouraging private firms to grow tongkat ali plantations. In addition, the institute is
putting together a factory to process the plant after harvesting.

Penis enlargement pills

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Testosterone More than Just a Male
Hormone – 10 Things You Should
Know

Estrogen is widely highlighted as “the female hormone.” This sex hormone, produced in the
ovaries, is responsible for womanly features and reproductive functions. As women begin to go
through menopause, many consider supplementing decreased estrogen through hormone
replacement therapy (HRT) to lessen the symptoms - hot flashes, sweats, and moodiness - of
“the change of life”.

However, did you know that testosterone is equally important to a woman? Here are 10 things
we’ve compiled that many people do not know about this important hormone:

1. Testosterone is produced in the ovaries and is the precursor to estrogen.

2. A woman's testosterone levels are highest in the early twenties. Testosterone levels begin to
decrease in men during their early twenties and in women in the mid-twenties.

3. The decrease in sex drive seen thereafter is often due to oral contraceptives that suppress all
sex hormone production (testosterone, estrogens and progesterone).

4. Before and after menopause, testosterone benefits to women include: improved relief of
menopause symptoms, increased energy levels, enhanced feelings of well-being, decreased
breast tenderness, improved sexual desire, increased sexual sensitivity, increased the frequency
of coitus, and enhanced orgasm.

5. With the cessation of 80% of hormonal production, a menopausal woman suffers from
estrogen, progesterone and testosterone deficiency.

6. About half of a woman’s testosterone comes from the ovaries, and as a result women whose
ovaries are removed before menopause lose about half their natural testosterone.

7. Menopausal women have low to non-detectable testosterone levels with resultant loss of
libido and increase in body fat.

8. The replacement of estrogen alone does not correct an absent sex drive, loss of muscle tone
and general lack of mental “get-up-and-go.”

9. Estrogen replacement therapy can also lead to decreased testosterone production, leading
some postmenopausal women to go to their doctors with concerns about lack of energy and
libido despite already being on hormone replacement therapy.

10. In a study at the Baton Rouge Menopause Center on the treatment of 4,000 patients, a
combination of estrogen and testosterone has shown a reduction in the incidence of breast
cancer to less than half the national average. On average, there is one cancer discovered for
every 100 mammograms performed. In those patients on testosterone therapy, there is only one
cancer in every 1,000 mammograms-a decrease of 90 percent.

As the top ten lists suggests, testosterone deficiency, also known as Andropause, is creating a
hot flash in the medical community in treatment of females with ovarian cancer, patients who
undergo hysterectomies, and women above age 40. Because clinical trials on the long-term
effects of this treatment are still underway, testosterone therapy remains controversial.
However, such experts as psychiatrist Dr. Susan Rako, author of “The Hormone of Desire: The
Truth About Sexuality, Menopause and Testosterone,” and clinician Dr. William Regelson,
M.D., author of “The Superhormone Promise” are part of a growing wave of publications
heralding the importance of this hormone to women’s health. These and other pioneers suggest
that using the hormone at the right dose can help some women ward off the bone-thinning
disease osteoporosis, maintain muscle mass, improve energy, keep the zing in their sex lives,
and generally feel better.

Finding the right balance is imperative. Rather than a “one size fits all” prescription, doctors
agree that a dosage tailored to the individual’s needs is key. Prescription options include taking
testosterone or DHEA (dehydroepiandrosterone) pills, lozenges, patches, gels, and injections.
Disadvantages of this therapy include risks of liver toxicity and lower levels of HDL (the
“good” cholesterol). Common side effects caused by high doses of DHEA include acne,
menstrual irregularities, irritability, and restlessness

One of the most effective non-prescription herbs for naturally increasing testosterone
production is Tongkat Ali, a strong strain of ginseng grown in the rainforests of Malaysia. This
herb stimulates the luteinizing hormones (LH) responsible for naturally stimulating testosterone
production in the body. Scientific studies show this herb to be two times more effecting in
producing the hormone than Tribulus Terrestris. There are currently no known side effects
associated with these two herbs.

The largest North American distributor of this Tongkat Ali is a Chicago minority women run
Herbal Powers. The company markets the product in sixty capsule pills and an herbal coffee,
Enerdisia. Information on their products and associated retailers is available at
www.herbal-powers.com.

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Tongkat Ali - Malaysia's very own 'Viagra

KUALA LUMPUR, Dec. 28 (Kyodo) - By: Vivian Ho

Long before Viagra hit the headlines, a local herb known as ''Tongkat Ali,'' Eurycoma Longifolia
Jack, has made many Malaysian men rise to the occasion. The root of the plant is said to have
aphrodisiac properties and will enhance male sexual libido besides other medicinal values such
as treatment for dysentery, glandular swelling, fever, malaria and other ailments.

In the old days, the roots, found only in the wild tropical forest of Southeast Asia, had to be
brewed for long hours to get a bitter extract. Now, Tongkat Ali, which literally means Ali's cane,
is conveniently packed in pill or ''tea-bag'' form and mixed with regular coffee or tea for an extra
''lift.''

Tongkat Ali coffee and tea are now the latest crazes to hit town, widely sold in Malaysia's
ubiquitous roadside hawker stalls, supermarkets and even at eateries in posh hotels.

''It is my most popular drink now. Before, it used to be ginseng coffee, now it's Tongkat Ali
drinks,'' hawker-stall operator Abdul Rahim said.

A company selling Tongkat Ali pills over the Internet touted that those who take the pills for a
week will find their testosterone level increases up to 480%. ''It is five times stronger than
ginseng,'' another company claimed. A bottle containing 60 capsules is sold for 148.16 ringgit
(about 39 dollars).

Another company, selling Tongkat Ali pills claimed that Tongkat Ali is better than the famous
blue pill Viagra.

''You don't need a doctor's prescription to buy Tongkat Ali pills and there is no side effect,''
President Yeo said.

And while Viagra could be fatal to some heart patients, Tongkat Ali is said to be good for them
and those suffering from high blood pressure.

''This is not Viagra, which only makes a man 'ready' in a relatively short time. Intake of Tongkat
Ali must be maintained daily to ensure a healthier lifestyle,'' Yeo said.

Local scientist, Johari M. Saad of Malaya University, maintains the aphrodisiac properties
synonymous with the plant have been ''overly exploited commercially'' and with some
''misconceptions,'' agreed there are components that ''when prepared scientifically, do show
testosterone enhancing properties.''

''If testosterone deficiency is the cause of mellowed 'man-ism' in you, then probably Tongkat Ali
will provide you some extra push. However, if you are really 'padam' (Malay for burned out)
then, see your doctor. Probably Viagra is for you,'' Johari said. PADAM is also an acronym for
Partial Androgen Deficiency in Aging Men Syndrome, the medical term for male menopause.
Johari and his team did a study on PADAM and the use of Tongkat Ali as an alternative to
testosterone therapy.

''These early studies provide very promising data on the potential of this plant as an alternative
to testosterone therapy in addressing the physiological changes in aging due to testosterone
deficiency,'' he said.

Tongkat Ali pills is sold in Brunei, Taiwan, Thailand, Japan, and Singapore as well as in
Malaysia. A 30-capsule bottle of Tongkat Ali pills costs 109.90 ringgit. Yeo believes Tongkat
Ali has a market potential of about 5 million ringgit a month.

Men are not the only ones looking for stimulation. Alongside Tongkat Ali coffee are beverages
laced with ''manjakani,'' touted as a way to keep vaginal muscles toned. The drink is also said to
help regulate menstrual flow, but men are said likely to suffer constipation if they try the drink.

Then there is Kacip Fatimah (Labisia Pumila) drinks, made from a traditional herb and believed
to cure problems such as irregular menstrual cycles and vaginal discharges.

But unlike Tongkat Ali drinks, drinks meant for women are not as widely available. They are
mostly sold through the direct market.

Source: The Kyodo News Service
28 December 1999

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Tongkat Ali - TestosteroneBooster

By: May Ling Lai

I'm one of the lucky ones who have been blessed with good
genetics and can eat pretty much anything I want without
exercising. In fact, I was famously guilty for such phrases as
"Why are you running? Is there not a cab available?"

But age and the stress of a 12 hour work day started to take
its toll as I rounded a quarter century. Hey, I know 25 years
old is still young, but when your ass starts to sag, you tend to
be pretty quick to change your tune.

In my city, the "it" thing to do is run along the lakefront.
Everyone and their dog is out, enjoying the beauty of the lake
and excitement of half nudity in a city that is fully covered and
freezing in snow for most of the year. I started running with
one of my long- legged, gorgeously athletic, genetically blessed
girl friends (she's single by-the-way). We had only run about a
half a mile, when huffing and puffing, I had to stop and do the
walk of shame, as I let her run ahead of me so that she could
"at least try to get a workout." Sad - I know - but I'd really
never ran at all in my life. Two weeks passed before I tried
again with similarly pathetic results.

A friend of mine suggested an herbal coffee called Enerdisia
that was enriched with Tongkat Ali. About a week and a half
after my last pathetic attempt, I drank a cup at 1pm to get
energy for the later part of my work day. Then I started out on
an afternoon run with my friend. We did a mile and half. It
wasn't easy, but it was twice as far as I had run before.

I continued drinking it everyday. I liked it better than coffee,
because it's less acidic. After about 3 weeks, I was running 3
miles a day two to three times a week. My stomach looked
good enough to be acceptable for the Britney Spears outfits
that were coming out. And my ass sag-gage had gone down.

Though it is probably preferable to do your research first
before drinking a new energy beverage, my three weeks of
success sparked a curiosity in the ingredient responsible for
my atheleticism.

Tongkat ali, latin name Eurycoma longifolia, is a root that
grows in the rainforests of Southeast Asia. Similar to Tribulus,
the herb works by affecting the lutenizing hormones in the
body, which signal testosterone production. From the articles I
read, I learned that Tongkat Ali boosts testosterone in lab
mice by 440%.

I had the opportunity to speak with a representative at the
company that makes the coffee I now drink regularly. They
mentioned tongkat ali has 17 different medicinal benefits that
have been studied and tested. As to safety, the representative
told me that acute and chronic tests had been done on mice.
Luckily for them, there were no side effects. The acute test
consisted of a large amount, equivalent to 300 doses, given to
the mice in a short period of time. The chronic test watched
the subjects for 90 days giving the test subjects a daily 200mg
dose (they suggest 100mg for a daily dosage). Again, no side
effects were witnessed.

There were a number of other interesting benefits to the
product, above and beyond the increase in energy, stamina,
and endurance I was already experiencing. Tongkat Ali is
diuretic, meaning that it gets rid of water retention in the body.
The herb, apparently, was traditionally used as a potent
aphrodisiac for men. For women after pregnancy, the herb can
specifically help to tighten the abdomen and bring the body
back toward "sensual wellness". My best friend who just had a
baby and the "romanitic issues asociated with it" dittoed this
last attribute, with a big smile on her face.

I'm not a body builder and I don't regularly use a bunch of
different products to be able to compare them with
confidence. I'm just a regular person who tried something that
worked better than I expected.

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Anti-cancer compound found in Malaysian plant.

Last Updated: 2002-07-22 10:04:13 -0400 (Reuters Health) KUALA LUMPUR (Reuters) -
Research has shown that a Malaysian jungle plant widely believed to be an aphrodisiac could
also be effective against cancer and HIV, a newspaper reported on Sunday.

The New Sunday Times said early results from a study conducted by a Malaysian
government-sponsored agency and the Massachusetts Institute of Technology found that
some chemical constituents of the "tongkat ali" plant show potent anti-cancer and anti-HIV
activity. HIV is the virus that causes AIDS.

Forest Research Institute Malaysia director-general Abdul Razak Mohd Ali was quoted by the
newspaper as saying that initial laboratory work had shown that the chemical constituents
could be more effective than existing anti-cancer drugs.

Tongkat ali, scientifically known as Eurycoma longifolia, is reputed to boost the male sex drive,
and villagers have long used it to improve blood circulation and cure skin diseases.

Malaysia last year patented the plant, which also grows in Thailand and Indonesia, to give the
country a big push into the herbal medicine industry.

Another Malaysian-US study had also shown that the bintangor tree found in Malaysia's
eastern state of Sarawak is a source of an anti-AIDS compound--calonolide. It is currently
undergoing clinical trials in the United States.