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Home > Medicinal Herbs and Plant Database > Malaysian Herbal Monograph > Eurycoma longifolia Jack
Malaysian Herbal Monograph
  • Written by Raja Nazatul Izni Raja Shahriman Shah
  • Updated on September 1, 2022

Tongkat Ali Root

Eurycoma longifolia Jack

Simaroubaceae

a
(a)
b
(b)
c
(c)
d
(d)
e
(e)
roots
(f)

Figure 1 : E. longifolia. (a)-(c) Whole plant; (d) fruits; (e) root from matured plant; (f) root from young plant. (Photos courtesy of Thiyagu, MARDI, 2012; GlobinMed, 2012)

DEFINITION

Tongkat ali root consists of dried root or underground parts of E. longifolia Jack .

SYNONYM

None

VERNACULAR NAMES

Bedara merah, bedara pahit, bedara puteh, lempedu pahit, pasak bumi, payong ali, petala bumi, penawar pahit, tongkat ali, tongkat baginda, setunjang bumi (Malaysia) [ 1 ].

CHARACTER

The yellowish white tap root is tough, woody and long. It has slight pungent smell and very bitter taste.

IDENTIFICATION

Plant Morphology

A slow growing plant attaining a maximum height of 10-18 m, often spindly unbranched crowned by an umbrella-like rosette of leaves with reddish brown petioles. Leaves compound, evenly pinnate, spirally arranged reaching 1 m in length; each compound leaf consists of 10-40 leaflets, lanceolate to obovate-lanceolate; each leaflet is about 5-20 cm long, 1-6 cm wide, much paler on the ventral side. Inflorescence axillary, in large brownish red panicle, very pubescent with very fine, soft, glandular trichomes. Flowers are dioecious; petals small, lanceolate to ovate obovate-oblong (4.5-5.5 mm long and 2-3 mm wide), very fine pubescent; styles rather long with peltate 5 (-6)-lobed stigma, elevated about 1 mm above the carpels. Drupe is about 10-20 mm long, 5-12 mm wide, hard, ovoid, yellowish brown when young and brownish red when ripe. Root is pale yellowish colour; wild collected root has only tap root of 0.5-1.5 m while cultivated root has tap root with abundance of lateral roots less than 1 m.

Microscopy

The root powder has fairly numerous vessels fragments with hexagonal pits that are usually are associated with thin-walled fibres or xylem and thin-walled parenchyma cells. Larger fibres have thick dentate or sometimes septate wall. The very large pericyclic fibre is only found in fragments. Cork cells are thick-walled, isodiametric in shape and found associated with the fibres. Brown pigments are fairly numerous and found in small and large fragments. Prism-shaped calcium oxalate crystals are also present. The abundant starch granules are mostly simple and spherical or oval in shape. Numerous starches have hilum.

m1
(a)
m2
(b)
m3
(c)
m4
(d)
m5
(e)
m6
(f)

Figure 2 : Microscopic images of E. longifolia root powder. (a) A vessel fragment with hexagonal pits (magnification 100X); (b) cork cells and fibre (magnification 400X); (c) pericyclic fibre (magnification 100X); (d) thick reticulated vessel (magnification 400X); (e) prism-shaped calcium oxalate crystal (magnification 100X); (f) starch granules (magnification 100X). [Scale bars: a, c, e, f =100  µm; b, d =20  µm]

Colour Tests 

Observed colour of solution after treatment with various reagents:

H2SO4(conc.)Dark brown 
HCl (conc.)Yellow to light green
5% NaOHYellow
5% KOHYellow
25% NH4OHLight yellow
5% FeCI3Yellow

Thin Layer Chromatography (TLC)

Figure 3 : TLC profiles of eurycomanone (S) and methanol extract of E. longifolia root (L) observed under (a) UV at 254 nm (b) UV at 366 nm 

Test Solutions Weigh about 2.0 g of E. longifolia dried root powder in a round bottom flask, add  10 mL of methanol and stir. Heat in a water bath of 80°C for 15 min and allow to cool. Filter the mixture and use the filtrate as the test solution.
Standard solution Dissolve 5.0 mg eurycomanone in 10 mL methanol to give 500 µg/mL solution.
Stationary Phase HPTLC Silica gel 60 F254, 5 x 10 cm
Mobile phase n-Butanol:acetic acid:water, 4:1:5
Preparation of butanol:acetic acid:water, 4:1:5
Saturate butanol with water at the ratio of 1:1, in a separation funnel for 12 hours. Collect the upper organic layer and saturate it with acetic acid and water at a ratio of 4:1:5, in a separation funnel for 12 hours. Collect the upper organic layer and use as the mobile phase.
Application
  1. Eurycomanone standard solution (S); 10 µL, as a band
  2. Methanol extract of E. longifolia root (L); 10 µL, as a band
Development distance 8 cm
Drying Air drying
Detection
  1. UV 254 nm;
  2. UV 366 nm.

High Performance Liquid Chromatography (HPLC)

Test solution Extract about 1.0 g of E. longifolia dried root powder in a 50 mL screw-capped conical flask with 20 mL of ethanol. Place it in a water bath of 80°C for 1 hr. Centrifuge at 5000 rpm for 20 min. Evaporate the supernatant until completely dry. Reconstitute with 2 mL methanol. Filter the solution through a 0.45 µm syringe filter and inject the filtrate into the HPLC column.
Standard solution Dissolve 2.0 mg of eurycomanone standard in 10 mL of methanol to give 200 µg/mL solution.
Chromatographic system

Detector: UV 244 nm
Column: C18  (5 µm, 4.6 mm I.D x 150 mm)
Column oven temperature: 40oC
Flow rate: 0.7 mL/min
Injection volume: 2 µL
Mobile Phase (gradient mode)

Run Time

(min)

A – Acetonitrile
(%)

B – 0.1 % formic acid
(%)

0

 10.0 90.0

7

 12.5 87.5
9 12.5

87.5
11

15.0

85.0
13

15.0

85.0
18

90.0

10.0
22

10.0

90.0
35

10.0

90.0
System suitability requirement

Perform at least five replicate injections of the standard solutions (200 µg/mL).The requirements of the system suitability parameters are as follow:

  1. Symmetry factor (As) is not more than 1.5.
  2. Percentage of relative standard deviation (RSD) of the retention time (tr) for eurycomanone is not more than 2.0%.
Acceptance criteria
  1. Retention time (tr) of eurycomanone in the test solution is similar to the tr of the standard solution.
  2. The resolution (Rs) value between peak of eurycomanone and peak A in the test solution should not be less than 1.5.
  3. The ultraviolet (UV) spectrum of eurycomanone in the test solution is similar to the UV  spectrum of the standard solution (optional supportive data).
hplc chamotograms

Figure 4 : HPLC chromatogram of eurycomanone standard solution (200 µg/mL) at tr = 10.023 min

hplc figure 5

Figure 5 : HPLC chromatogram of ethanol extract of E. longifolia showing peak corresponding to eurycomanone (tr = 10.017 min) and peak A (tr = 10.603 min).

UV spectrum Eurycoma longifolia

Figure 6 : UV spectrum of eurycomanone standard solution (200 µg/mL) and ethanol extract of E. longifolia root

PURITY TESTS

Foreign Matter
Not more than 2%
Ash Contents
Total ash Not more than 4%
Acid-insoluble ash Not more than 1%
Loss on Drying
Not more than 10%
Extractive Values
Water-soluble extracts
Hot method Not less than 6%
Cold method Not less than 3%
Ethanol-soluble extracts
Hot method Not less than 3%
Cold method Not less than 1%

SAFETY TEST

Heavy Metals
Arsenic Not more than 5.0 mg/kg
Mercury Not more than 0.5 mg/kg
Lead Not more than 10.0 mg/kg
Cadmium Not more than 0.3 mg/kg
Microbial Limits
Total bacterial count Not more than 105 cfu/g
Total yeast and mould count Not more than 104 cfu/g
Bile-tolerant gram negative Not more than 104 cfu/g
Specific Pathogens
Salmonella spp. Absent in 25 g
Escherichia coli Absent in 1 g
Staphylococcus aureus Absent in 1 g
Pseudomonas aeruginosa Absent in 1 g

CHEMICAL CONSTITUENTS

Aqueous extract of the roots has been found to contain quassinoids (e.g. eurycolactones A-E, eurycomalides A-B, eurycomalactone, 6α-hydroxyeurycomalactone, 7α-hydroxyeurycomalactone, eurycomanone, 13α(21)-epoxyeurycomanone, 12,15-diacetyl-13α(21)-epoxy-eurycomanone,12-acetyl-13,21-dihydroeurycomanone, 15-acetyl-13α(21)-epoxyeurycomanone, 3,4ε-dihydroeurycomanone, 13,21-dihydroeurycomanone, eurycomanol, 13β,18-dihydroeurycomanol, 13β, 21-dihydroxyeurycomanol, eurycomanol-2-O-β-D-glycopyranoside, 11-dehydroklaineanone, 15β-hydroxyklaineanone, 14,15β-dihydroxyklaineanone, 5α,14β,15β-trihydroxyklaineanone,15β-O-acetyl-14-hydroxyklaineanone, 6α-acetoxy-14,15β-dihydroxyklaineanone, 6α-acetoxy-15β-hydroxyklaineanone, laurycolactones A-B, longilactone, dehydroxylongilactone, 2,3-dehydro-4α-hydroxylongilactone, ailanthone, (α/β-epoxide) ailanthone, chaparrinone (α-methyl), 3,4ε-dihydrochaparrinone, picrasinoside B, klaineanolide B, iandonoside B, eurycomaoside, 16-α-O-methylneoquassin, samaderin B and glaucarubolone), canthin-6-one alkaloids (e.g. canthin-6-one, 9-methoxycanthin-6-one, 5,9-dimethoxycanthin-6-one, 9,10-dimethoxycanthin-6-one, 11-hydroxycanthin-6-one, 1-hydroxy-11-methoxycanthin-6-one, 10-hydroxy-9-methoxycanthin-6-one, 11-hydroxy-10-methoxycanthin-6-one, 11-O-β-D-glucopyranosylcanthin-6-one, canthin-6-one-3N-oxide, 9-methoxycanthin-6-one-3N-oxide and 9-methoxy-3-methylcanthin-5,6-dione), β-carboline alkaloids (e.g. β-carboline-1-propionic acid, 7-hydroxy-β-carboline-1-propionic acid, 7-methoxy-β-carboline-1-propionic acid, and 1-methoxymethyl-β-carboline), squalene-type triterpene (e.g. eurylene and 11/14-deacetyl eurylene), biphenylneolignans (e.g. 2,2’-dimethoxy-4-(3-hydroxy-1-propenyl)-4’-(1,2,3-trihydroxypropyl) diphenyl ethers (isomer), 2-hydroxy-3,2’,6’-trimethoxy-4’-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)-biphenyl and 2-hydroxy-3,2’-dimethoxy-4’-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)-biphenyl) and others (e.g. isoleucine, calcium, magnesium and potassium) [ 10 , 23 , 24 ].

Methanol extract of the roots has been found to contain quassinoids (e.g. eurycolactones A-F, eurycomalides A-B, eurycomalactone, 6α-hydroxyeurycomalactone, 6-hydroxy-5,6-dehydroeurycomalactone, 5,6-dehydroeurycomalactone, eurycomanone, 13β,21-dihydroxyeurycomanol, 14,15β-dihydroxyklaineanone, 5α,14β,15β-trihydroxyklaineanone, laurycolactones A-B, longilactone, 6-dehydroxylongilactone, 2,3-dehydro-4α-hydroxylongilactone and pasakbumin B-C), canthin-6-one alkaloids (e.g. canthin-6-one, 1-hydroxycanthin-6-one, 9-hydroxycanthin-6-one, 5-hydroxymethylcanthin-6-one, 5-methoxycanthin-6-one, 9-methoxycanthin-6-one, 10-methoxycanthin-6-one, 1-hydroxy-9-methoxycanthin-6-one, 4-hydroxy-5-methoxycanthin-6-one, 8-hydroxy-9-methoxycanthin-6-one, 5-hydroxymethyl-9-methoxycanthin-6-one, 4,5-dimethoxycanthin-6-one, 9,10-dimethoxycanthin-6-one, canthin-6-one 9-O-β-glucopyranoside, canthin-6-one-3N-oxide, 9-hydroxycanthin-6-one-3N-oxide and 9-methoxycanthin-6-one-3N-oxide), β-carboline alkaloids (e.g. β-carboline-1-propionic acid, 7-methoxy-β-carboline-1-propionic acid, methyl β-carboline-1-carboxylate, n-pentyl β-carboline-1-propionate and picrasidine L), triterpenes (e.g. eurylene,  mixture of β-sitosterol and stigmasterol, and β-sitosteryl glucoside) and others (e.g. scopoletin, fraxidin, scopolin, ρ-hydroxybenzaldehyde, syringic aldehyde, 2,4’-dihydroxy-3’-methoxyacetophenone, 2,3-dihydroxy-1-(4’-hydroxy-3’-methoxyphenyl)-propan-1-one, 3-hydroxy-1-(4’-hydroxy-3’-methoxyphenyl)propan-1-one, threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol, vanillic acid, protocatechuic acid, nicotinic acid, syringic acid, sodium syringate, sodium ρ-hydroxybenzoate, lariciresinol, erythro-1-C-syringylglycerol, threo-1-C-syringylglycerol, erythro-guaiacylglycerol, threo-guaiacylglycerol, iandonone, adenosine, guanosine, thymidine, alanine, proline, arginine, serine, glucose and fructose) [ 11 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].

Ethanol (50%) extract of the roots has been found to contain quassinoids (e.g. eurycomanone, 13,21-dihydroeurycomanone, 13α(21)-epoxyeurycomanone, longilactone, eurycomalactone, 14,15β-dihydroxyklaineanone, eurycomanol, eurycomanol-2-O-β-glucopyranoside) and a canthin-6-one alkaloid (e.g. 9-methoxycanthin-6-one) [ 32 , 33 , 34 ].

Volatile components were also detected in the aqueous and methanol root extracts, e.g. 3-methylbutanal, 1-butanol, 1-pentanol, 2-hexadecanol, acetol, nonanal, acetic acid, 2-methylhexanol, benzaldehyde, [S-(R*,R*)]-2,3-butanediol, butyrolactone, 2-furanmethanol, 3-methylbutanoic acid, 2(5H)-furanone, curcumene, hexanoic acid, butylated hydroxytoluene, 1-(1H-pyrrol-2-yl)-ethanone, (R)-(−)-massoilactone, 1H-pyrrole-2-carboxaldehyde, 3-phenoxy-1-propanol, octanoic acid, [1R,2S,5R]-1’-[butyn-3-one-1-yl]-menthol, 2-phenoxyethanol, ethyl p-ethoxybenzoate, nonanoic acid, 4-ethynyl-4-hydroxy-3,5,5-trimethyl-2-cyclohex-1-enone, 2,4-bis(1,1-dimethylehtyl)phenol, diethyl phthalate, benzoic acid, 2,3,6,7-tetrahydro 4a,8a-butano-[1,4]dioxino[2,3-b]-1,4dioxin [ 35 ].

MEDICINAL USES

Use described in folk medicine, not supported by experimental or clinical data

The root has been traditionally used for fever, afterbirth medication, boils, wounds and ulcer, syphilis, and bleeding gums, aches, dysentery, glandular swelling, edema and tonic [ 3 , 4 ].

Biological and pharmacological activity supported by experimental data

Antimalarial activity

Eurycomanone, pasakbumi B and 7-methoxy--carboline-1-propionic acid isolated from E. longifolia root exhibited potent anti-plasmodial activity against Plasmodium falciparum
[ 5 ]. It was also shown that eurycomanone, 13,21-dihydroeurycomanone, 13α(21)-epoxyeurycomanone, eurycomalactone, and 9-methoxycanthin-6-one displayed anti-plasmodial activity against chloroquine-resistant Gombak A isolate of Ρ. falciparum with IC50 in the range of 0.23-1.56 µg/mL [ 6 ]. A mixture of semi-purified root extract (13β,18-dihydroeurycomanol, eurycomanol-2-О-β-D-glucopyranoside, eurycomanol and eurycomanone) of 0.07-5.00 µg/mL demonstrated more than 50% inhibition  of P. falciparum strain
[ 7 , 8 ].

The standardised methanol extract of E. longifolia root at the concentration of 10, 30 and 60 mg/kg BW in combination with artemisinin given orally to mice for 3 days showed suppression of 63, 67 and 80% of Plasmodium yoelii infection in mice, respectively, whilst 80% suppression of P. yoelii infection was observed with subcutaneous treatment of E. longifolia (10 mg/kg BW) combined with artemisinin [ 9 ].

Cytotoxicity activity

Eurycomanone isolated from E. longifolia roots exhibited potent cytotoxicity effect with IC50 value of  45 ± 0.15 μg/mL on hepatoma (HepG2) cells through apoptosis mechanism
[ 10 ].

9-methoxycanthin-6-one, 9-methoxycanthin-6-one-N-oxide, 9-hydroxycanthin-6-one and 9-hydroxycanthin-6-one-N-oxide isolated from E. longifolia roots exhibited cytotoxic effects against human cancer cell types including breast, colon, fibrosarcoma, lung, melanoma, KB and murine lymphocytic leukemia (P-388) with ED50 in the range of 1.4 to 11.7 µg/mL. Eurycomanone was active against all cells above including vincristine-resistant KB cells (ED50 0.2-11.3 µg/mL), except P-388 cells [ 11 ]. 

Eurycomanone, 21-dihydroeurycomanone and 14,15β-dihydroxyklaineanone from E. longifolia roots showed potent cytotoxic effect against KB cells with IC50 values of 0.98, 0.81 and 0.96 µM, respectively [ 6 ].

Aphrodisiac activity

Aqueous extract of E. longifolia root (30, 60, 90, 150 mg/kg) given via oral gavage to Sprague Dawley male rats for 28 days enhanced sexual activities and sperm quality (sperm count, motility, morphology and viability) of the treated rats [ 12 ].

Chloroform, methanol, butanol and water fractions of E. longifolia root given orally to 3-4 month old male Sprague Dawley albino rats for 10 days showed a dose-dependent increase in mounting frequency from 5.3 (400 mg/kg) to 5.4 (800 mg/kg), 4.9 to 5.4, 4.8 to 5.2 and 5.2 to 5.3, respectively [ 13 ]. These fractions (500 mg/kg) contributed towards sexual motivation activity in adult, middle-aged male albino mice and in retired breeders [ 14 ], as well as enhanced sexual qualities of middle-aged male rats [ 15 ].

Methanol, chloroform, water and butanol fractions of E. longifolia root (800 mg/kg) given via oral gavage to 9-month old Sprague Dawley rats for 10 days  showed changes in sexual behaviour such as increased orientation activities towards the receptive female rats (anogenital sniffing, licking and mounting), increased genital grooming towards themselves and restricted movements to a particular area of the cage [ 16 ]. The fractions (800 mg/kg) were also found to promote sexual arousal in sexually sluggish old male rats [ 17 ]. Additionally, these fractions (800 mg/kg) given orally for 12 weeks to testosterone-stimulated castrated intact male rats revealed pro-androgenic property as evidenced by the enhanced growth of the laevator ani muscle [ 18 ].

Anti-diabetic property

Antihyperglycaemic activity of aqueous extract of E. longifolia root (150 mg/kg body weight) was observed in streptozotocin-induced hyperglycaemic Sprague Dawley rats after 10 days of treatment [ 19 ].

Anxiolytic activity

Chloroform, methanol, butanol and water fractions of E. longifolia root (0.3 g/kg) were administered by oral gavage to inbred adult albino mice (35-40 g) exerted anxiolytic effect
[ 20 ].

Anti-osteoporosis

Supplementation of E. longifolia root aqueous extract given to 12-month old orchidectomised Sprague Dawley rats for 6 weeks showed maintenance of bone calcium level [ 21 ]. 

Hormonal Imbalances Activity

Water extract of Eurycoma longifolia roots (500 mg/kg) showed decreased in serum follicle stimulating hormone (FSH) (P < 0.001, 4.25 ± 0.22 mIU/ml) and luteinising hormone (LH) (NS, 4.07 ± 0.12 mIU/ml), while there was a significant increase in progesterone (P < 0.05, 2.48 ± 0.08 ng/ml) and estrogen (P < 0.05, 11.02 ± 0.13 pg/ml) levels in ovariectomised rat when compared to untreated group. At a dosage of (100, 300 and 500) mg/kg of E. longifolia extract showed a non-significant but increasing trend in serum calcium, phosphate, bone alkaline phosphatase and testosterone levels. [51]

Nephroprotective Activity

Two concentration of water extract of E. longifolia (EL) roots, namely EL 200 (EL 200 mg/kg + 200 mg/kg PCM) and EL 400 (EL 400 mg/kg + 200 mg/kg PCM) administered orally to forty paracetamol (PCM)-induced-nephrotoxicity male 12-week-old Wistar for 14 days showed significant dose-dependent protection against PCM-induced changes in terms of increase creatinine clearance rate (EL200= 0.61 ± 0.22ml/min; p < 0.01 , EL400= 0.87 ± 0.26 ml/min; p < 0.001), increase of serum total protein  (EL200= 9.4 ± 1.4 g/dl; p<0.05 , EL400= 10.1 ± 1.6 g/dl ; p < 0.05), and increase of serum albumin  (EL200= 3.1 ± 0.8 g/dl; p < 0.05 , EL400= 3.1 ± 0.3 g/dl; p < 0.05),drop in serum creatinine (EL200= 0.9 ± 0.1 mg/dl; p < 0.05 , EL400= 0.8 ± 0.16 mg/dl; p < 0.05) and drop in blood urea (EL200= 21.7 ± 3.4 mg/dl; p < 0.05 , EL400= 18.0 ± 2.3 mg/dl; p < 0.05) as well as minimal degenerative changes in kidney through histopathological examination. [52]

Clinical studies

Male patients suffered from late onset of hypogonadism aged between 28 to 70 years old were given daily oral dosage of 200 mg of standardized aqueous extract of E. longifolia root for 1 month and exhibited significant improvement in testosterone level and scores of the Ageing Male’s Symptoms [ 22 ].

A  clinical trial to study analyse the improvement of the quality of life, physical performance, and sexual well-being in men during intake of a freeze-dried aqueous extract from the roots of E. longifolia. It is a randomized, double-blind, placebo-controlled and parallel group which involved 109 men between 30 and 55 years of age. The patients took either treatment of 300 mg of aqueous extract of E. longifolia or placebo for a duration of 12 weeks. Result showed significant improvement in pysical functioning doamain based on SF-36 questionnaire (p=0.006), higher score in the overall Erectile Function domain in International Index of Erectile Function (p<0.001), sexual libido (14% by week 12), sperm motility based seminal fluid analysis at 44.4% and semen volume at 18.2% [ 44 ]

A randomized double blind placebo-controlled trial involving 40 Malaysian patients (male) was performed in which the ratio of Testosterone (T) to Epitestosterone (E) was analyzed. The treatment group was given 300mg of the freeze-dried water extract of E. longifolia root or placebo for a period of 12 weeks. Each subject consumed four capsules per day containing herbal extract or placebo. Each capsule contained 75mg of freeze-dried water extract of E. longifolia root. Blood samples were collected for routine health checks. Physical fitness testing was performed during the second, third and fourth visit. Results showed in both treatment groups, the T/E ratio was normal and below 4. A significant increase in muscle strength was observed for the herbal group from baseline  (128.81 ± 5.63kg,p=0.0166) to 12 weeks (142.78±7.95 kg  compared to placebo (128±8.31kg, p=0.045) at 12 weeks in the back and leg strength test though muscular endurance, flexibility and body fat composition remain unchanged with 300mg daily dose of E. longifolia over 12 weeks. [45]

A randomized, double-blind, placebo-controlled, parallel-group study published in 2014 was carried out in California, United States on the effects of a freeze-dried water extract of E. longifolia on the sexual performance and well-being in men. This study is a two-arm study, whereby a sample size of 12 subjects in the intervention arm and 14 subjects in the placebo arm completed the study. The subjects were men aged 40-65 years who were given oral tablets of the extract or placebo of one tablet a day for 12 weeks. The results of the trial showed improvements in sexual performance, erection hardness scores, erectile dysfunction assessment and assessment of testosterone deficiency  in the E. longifolia group compared to the placebo group, although the satisfaction scores did not improve in both group. There were no occurrences of adverse events related to the study product combination of the herb in this trial and the product was well-tolerated. [46] 

A clinical study was conducted to investigate the effects of hot water extract of E. longifolia root on stress hormones and psychological mood state in stressed subjects. This clinical study was a randomized, placebo-controlled study involving a sample size of 64 subjects (32 men and 32 women) who had moderate stress levels (after screening). The subjects were prescribed either oral E. longifolia root extract of 200mg/day or placebo for four weeks, with their mood state, hormone profile, liver enzymes, weight and body fat percentage assessed. The results of the study showed that E. longifolia root extract was able to improve stress hormones (salivary cortisol and testosterone) and lower the mood states of tension, anger and confusion. There were no significant changes in the liver enzymes, body weight or body fat percentage. The only adverse events were three subjects who reported feeling fatigued in the first two weeks of the study (two subjects from the intervention group with one subject from the placebo group). [47] 

A randomized, double-blind, placebo-controlled, parallel study involving 81 subjects with relatively lower scores according to Scoring of Immunological Vigor (SIV) screening was recruited to study modulate human immunity in a middle-aged person. The treatment group was given 200 mg of a standardized E. longifolia water-soluble root extract capsule per day in week 0 and 4. SIV, immunological grade, immunological age, and other immune parameters were measured. At week 4, the SIV and immunological grade were significantly higher in the  E. longifolia group than those in the placebo group (p < 0.05). The numbers of total, naive, and CD4+ T cells were also higher in the  E. longifolia group than those in the placebo group (p < 0.05). No severe adverse events were observed. The results suggest that ingestion of the root water extract of  E. longifolia enhances comprehensive immunity in both middle-aged men and women. [48]

Another clinical trial to study the potential of  E. longifolia extract taken as an oral supplement to produce ergogenic effects in physically active elderly. It is a pilot study which involved 13 male and 12 females (57-72 years old). The participants took 200 mg (contained patented and standardized water soluble extract of  E. longifolia taken twice a day for 5 consecutive weeks. The effects shown by female and male participants vary in terms of serum testosterone level, muscle strength, and aging symptoms. Male participants showed significant increment in serum testosterone concentrations (Total testosterone = 4.42 + 1.15 ng/mL, p=0.0090, free testosterone 8.38 + 2.18pg/mL, p=0.0005) after 5 weeks of consumption. As for female participants, testosterone level (total and free testosterone) also shown some increment which might be contributed by the decline in serum Sex Hormone-Binding Globulin (SHBG) concentrations, however, the increment was within normal physiological levels of 0.063–0.836 ng/mL and 1.0–8.5 pg/mL, respectively. As for muscle strength, consumption of  E. longifolia oral supplement also showed significant increase in muscular force (determined by handgrip test) for both male and female participants. As for aging symptoms for females (determined by Aging Males’ Symptoms (AMS) and Aging Females’ Symptoms (AFS) questionnaire) the female participants reported to have improved significantly meanwhile for male participants, no improvement reported after the consumptions [49].

A randomized, double-blind, placebo controlled multicentre study using  E. longifolia standardized aqueous root extract was conducted to see testosterone levels and quality of life in aging male. The subjects were given either E. longifolia standardized aqueous root extract 100mg, 200mg or placebo daily for 12 weeks. There was a significant increase in the total testosterone levels at week 12 (p < 0.05) in the E. longifolia 100mg group ,( p < 0.001) in the E. longifolia 200mg compared to the placebo. No significant group between group differences in free testosterone levels were observed but a significant within-group increase occurred at weeks 12 (p < 0.001) in the E. longifolia 100mg group, (p < 0.001) in the E. longifolia 200mg group. The  ageing male symptom (AMS) and fatigue severity scale(FSS) showed significant reduction (p < 0.001) in total scores at all time-points within-and between-groups in both E. longifolia groups. Dehydroepiandrosterone(DHEA) levels significantly increased (P,0.05) within-group in both E. longifolia groups from week 2 onwards. Cortisol levels significantly (p < 0.01) decreased in the E. longifolia 200mg group, while muscle strength significantly (p < 0.001) increased in both E. longifolia groups at week 12 in the within-group comparison. There were no significant changes in sex hormone-binding-globulin(SHBG). No safety related clinically relevant changes were observed.The result showed that E. longifolia supplementation as low as 100 and 200mg in aged male subjects with low testosterone levels resulted in significant improvement in the total testosterone levels, accompanied by enhanced quality of life scores and reduced aging symptoms and fatigue as early as 4 and 2 weeks of supplementation [50].

SAFETY INFORMATION

Preclinical studies (Toxicological studies)

Acute toxicity

Oral administration of E. longifolia aqueous extract at 5000 mg/kg body weight via oral gavage on male Sprague Dawley rats within 24 hours did not produce any physical, behavioural and pathological changes in the liver, testes and kidneys. The oral LD50 for the extract was found to be more than 5000 mg/kg body weight [ 36 ]. A similar study demonstrated that oral administration of E. longifolia aqueous extract (2000 mg/kg body weight) to male and female Wistar rats also produced neither mortality nor changes in behavior or any other physiological activities [ 37 ].  

Aqueous ethanolic extract (50%) and its diethyl ether, n-butanol and water fractions were orally administered as a single dose to the Sprague Dawley mice. Observation was made after 48 hours after administration. The LD50 values ranged from 1.36-5.23 g/kg. The most toxic n-butanol fraction was found to be due to eurycomanone [ 33 ].

Oral single dose acute toxicity study on female Sprague Dawley rats (aged between 8 and 12 weeks old) using aqueous mixture of E. longifolia roots showed no toxic effects on the parameters observed, including behaviors, body weight, food and water intake. All rats were observed for 14 days prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality. No-observed-adverse-effect level (NOAEL) is more than 2,000 mg/kg body weight [ 43 ].

Sub-acute toxicity

Aqueous extract of E. longifolia root (up to 2400 mg/kg body weight) orally administered to Sprague Dawley rats for 28 days did not show significant changes in body weight, toxic symptoms such as piloerection, salivation and lacrimation, as well as in the biochemical and haematological parameters. No pathological changes were observed in the testes and kidneys. However, the livers from animals treated with extract of 1200 and 2400 mg/kg body weight exhibited hydropic changes in the livers [ 36 ].  

Male and female Wistar rats treated with up to 1000 mg/kg body weight of E. longifolia aqueous root extract for 28 days did not produce any mortality or toxic effect. No changes were observed in body and organ weights, histopathological analysis, blood biochemical parameters (glucose, creatinine, urea, aspartate transminase, potassium, sodium, total billirubin, total cholesterol, total protein, albumin and clotting time) and haematological parameters (white blood count, platelet and haemoglobin estimation) of both sexes [ 37 ].

Alcohol extract of E. longifolia showed signs of toxicity such as increased weights of liver, kidneys, spleen and testes on animals treated with 600 mg/kg body weight extract [ 38 ].

Sub-chronic toxicity

Aqueous extract of E. longifolia root (up to 1000 mg/kg body weight) orally administered for 90 days to both females and male Wistar rats for 90 days did not cause any mortality, clinical abnormalities and neurotoxicity effects [ 37 ].

Mutagenicity

Methanol-chloroform (1:1) extract of E. longifolia root (250 μg/mL) did not show any mutagenic effect on Salmonella typhimurium strains, TA 98 and TA 100 [ 39 ]. Reproductive toxicity Adult male Sprague Dawley rats exhibited no toxicity effects in testicular histology after oral treatment with 8 mg/kg body weight of aqueous E. longifolia root extract for 14 days [ 40 ].

Others (Adverse reaction, contraindication, side effect, warning, precaution)

Adverse reaction

Fresh E. longifolia root and E. longifolia-based products potentially cause allergic reaction based on an in vitro specific immunoglobulin E (IgE) immunoblotting test on sera of a patient with prawn allergy [ 41 ].

Herb-drug interaction

Co-administration of E. longifolia root water extract containing 0.0272 ± 0.0026% of eurycomanone and propanolol (80 mg) was found to reduce absorption of propanolol and decrease its bioavailability in healthy non-smoker young males [ 42 ].

DOSAGE

Generally, for healthy people, the recommended daily consumption of freeze-dried water extract of E. longifolia root is 50 mg to 200 mg [ 2 ].

STORAGE

Store below 30 °C. Protect from light and moisture.

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