Testosterone replacement is the choice of treatment in androgen-deficient osteoporosis. However, long-term use of testosterone is potentially carcinogenic. Eurycoma longifolia (EL) has been reported to enhance testosterone level and prevent bone calcium loss but there is a paucity of research regarding its effect on the bone structural parameters. This study was conducted to explore the bone structural changes following EL treatment in normal and androgen-deficient osteoporosis rat model. Thirty-six male Sprague-Dawley rats aged 12 months were divided into normal control, normal rat supplemented with EL, sham-operated, orchidectomised-control, orchidectomised with testosterone replacement, and orchidectomised with EL supplementation groups. Testosterone serum was measured both before and after the completion of the treatment. After 6 weeks of the treatment, the femora were processed for bone histomorphometry. Testosterone replacement was able to raise the testosterone level and restore the bone volume of orchidectomised rats. EL supplementation failed to emulate both these testosterone actions. The inability of EL to do so may be related to the absence of testes in the androgen deficient osteoporosis model for EL to stimulate testosterone production.
In most countries, millions of people are relying on herbal medicines as remedy for numerous ailments. In South-East Asia, Eurycoma longifolia Jack, also known as 'Malaysian ginseng' or Tongkat ali, is used to combat stress and disease and to improve physical strength. Moreover, the compounds of the roots of this plant are reported to have aphrodisiac and testosterone enhancing effects in the rat. Considering that human studies are not available, 76 of 320 patients suffering from late-onset hypogonadism (LOH) were given 200 mg of a standardised water-soluble extract of Tongkat ali for 1 month. The Ageing Males' Symptoms (AMS) according to the standardised rating scale and the serum testosterone concentration were taken. Results show that treatment of LOH patients with this Tongkat ali extract significantly (P < 0.0001) improved the AMS score as well as the serum testosterone concentration. While before treatment only 10.5% of the patients did not show any complaint according to the AMS scale and 35.5% had normal testosterone levels, after the completed treatment 71.7% and 90.8% of the patients showed normal values, respectively. Thus, Tongkat ali extract appears to be useful as a supplement in overcoming the symptoms of LOH and for the management of hypogonadism.
A simple validated LC-UV method for the phytochemical analysis of four bioactive quassinoids, 13alpha(21)-epoxyeurycomanone (EP), eurycomanone (EN), 13alpha,21-dihydroeurycomanone (ED) and eurycomanol (EL) in rat plasma following oral (200 mg/kg) and intravenous administration (10 mg/kg) of a standardized extract Fr 2 of Eurycoma longifolia Jack was developed for pharmacokinetic and bioavailability studies. The extract Fr 2 contained 4.0%, 18.5%, 0.7% and 9.5% of EP, EN, ED and EL, respectively. Following intravenous administration, EP displayed a relatively longer biological half-life (t1/2 = 0.75 +/- 0.25 h) due primarily to its lower elimination rate constant (k(e)) of 0.84 +/- 0.26 h(-1)) when compared with the t1/2 of 0.35 +/- 0.04 h and k(e) of 2.14 +/- 0.27 h(-1), respectively of EN. Following oral administration, EP showed a higher C(max) of 1.61 +/- 0.41 microg/mL over that of EN (C(max) = 0.53 +/- 0.10 microg/mL). The absolute bioavailability of EP was 9.5-fold higher than that of EN, not because of chemical degradation since both quassinoids were stable at the simulated gastric pH of 1. Instead, the higher log K(ow) value of EP (-0.43) contributed to greater membrane permeability over that of EN (log K(ow) = -1.46) at pH 1. In contrast, EL, being in higher concentration in the extract than EP, was not detected in the plasma after oral administration because of substantial degradation by the gastric juices after 2 h. Similarly, ED, being unstable at the acidic pH and together with its low concentration in Fr 2, was not detectable in the rat plasma. In conclusion, upon oral administration of the bioactive standardized extract Fr 2, EP and EN may be the only quassinoids contributing to the overall antimalarial activity; this is worthy of further investigation.
Microsatellite markers of an important medicinal plant, Eurycoma longifolia (Simaroubaceae), were developed for DNA profiling and genetic diversity studies.
Eurycoma longifolia Jack is an herbal medicinal plant of South-East Asian origin, popularly recognized as 'Tongkat Ali.' The plant parts have been traditionally used for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities, which have also been proved scientifically. The plant parts are rich in various bioactive compounds (like eurycomaoside, eurycolactone, eurycomalactone, eurycomanone, and pasakbumin-B) among which the alkaloids and quassinoids form a major portion. Even though toxicity and safety evaluation studies have been pursued, still a major gap exists in providing scientific base for commercial utilization and clearance of the Tongkat Ali products with regard to consumer's safety. The present review aims at reviewing the research works undertaken till date, on this plant in order to provide sufficient baseline information for future works and for commercial exploitation.
The present study investigated the effects of a standardized methanol extract of E. longifolia Jack containing the major quassinoid constituents of 13alpha(21)-epoxyeurycomanone (1), eurycomanone (2), 13alpha,21-dihydroeurycomanone (3) and eurycomanol (4) on the epididymal spermatozoa profile of normal and Andrographis paniculata induced infertile rats. The standardized MeOH extract at doses of 50, 100 and 200 mg/kg, the EtOAc fraction (70 mg/kg), and standardized MeOH extract at 200 mg/kg co-administered with the EtOAc fraction of A. paniculata at 70 mg/kg were each given orally to male Sprague-Dawley albino rats for 48 consecutive days. The spermatozoa count, morphology, motility, plasma testosterone level and Leydig cell count of the animals were statistically analyzed by ANOVA with a post-hoc Tukey HSD test. The results showed that the sperm count of rats given the standardized MeOH extract alone at doses of 50, 100 and 200 mg/kg were increased by 78.9, 94.3 and 99.2%, respectively when compared with that of control (p < 0.01). The low count, poor motility and abnormal morphology of the spermatozoa induced by the A. paniculata fraction were significantly reversed by the standardized MeOH extract of E. longifolia (p < 0.001). The plasma testosterone level of the rats treated with the standardized MeOH extract at 200 mg/kg was significantly increased (p < 0.01) when compared with that of the control and infertile animals. The spermatocytes in the seminiferous tubules and the Leydig cells appeared normal. Testosterone level was significantly higher in the testes (p < 0.01) than in the plasma after 30 days of oral treatment with the standardized MeOH extract. Interestingly, eurycomanone (2) alone was detected in the rat testis homogenates by HPLC-UV and confirmed by LC/MS, and may have contributed towards the improvement of sperm quality. Thus, the plant may potentially be suitable for the management of male infertility.
Eurycoma longifolia Jack, a small Simaroubaceae tree, known locally as 'Tongkat Ali' is popularly used as a sexual tonic in traditional medicine for aphrodisiac activity and improvement of fertility and male libido.
OBJECTIVE: To determine the efficacy of Tongkat Ali (Eurycoma longifolia) herbal extract on erectile function improvement.
METHODS: Comprehensive electronic databases were searched from inception through October 2014. Randomized controlled trials investigating Tongkat Ali compared to placebo were included. Outcome of interest was the improvement of erectile dysfunction. The difference of changes from baseline of the outcome between Tongkat Ali and placebo was pooled using weighted mean difference (WMD). Methodological quality of included studies was assessed using Jadad's quality scale and Cochrane's risk of bias.
RESULTS: Of the 342 articles identified, 2 studies involving a total of 139 participants were analyzed. No significance between group difference was found in the mean WMD of the change in the 5- item version of the international index of erectile function (IIEF-5) at week-12 (0.91; 95% CI: -1.50 to 3.33 with I(2)=89.5%, P-value=0.002) with statistical heterogeneity. Based on the subgroup analysis, significant improved IIEF-5 score of 2.15 (95% CI 1.03-3.27) was found in subjects with lower baseline IIEF-5 score, but this was not seen among those with higher baseline IIEF-5 score.
CONCLUSION: Based on current evidence, the herbal extract of Tongkat Ali may have clinical effect on erectile function. However, more efficacy trials are warranted to further support current evidence.
KEYWORDS: Alternative medicine; Erectile dysfunction; Eurycoma longifolia; Extract; Root; Tongkat Ali
This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta® to modulate human immunity in a middle-aged Japanese population. This randomized, double-blind, placebo-controlled, parallel study was conducted for 4 weeks. Eighty-four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty-three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p
In the local Malaysian context, herbal plants such as Eurycoma longifolia (Tongkat Ali), Orthosiphon stamineus (MisaiKucing), Ficus deltoidea (Mas Cotek), Zingiber officinale (Halia Bara) and Barringtonia racemosa (Putat) are known and widely used for its therapeutic properties. The first part of this study aims to screen for the anti-protozoal activity of these herbal plant extracts against Blastocystis sp. isolate subtype (ST) 3. Herbal extract with the highest efficacy was further fractionized into water and ethyl acetate fractions and tested against ST1, ST3 and ST5 Blastocystis sp. isolates. These isolates were also exposed to allopathic drugs, Metronidazole (MTZ), Tinidazole, Trimethoprim-sulfamethoxazole(TMP-SMX), Ketoconazole and Nitazoxanide for comparison purpose.
In the present study we examined the effect of E. longifolia methanol extract (TA164) on the GSH levels of P. falciparum infected erythrocytes and uninfected erythrocytes. Our study on parasite growth shows the IC50 and IC75 values of TA164 to be 0.17 g/ml and 6 g/ml respectively while for BSO was 25.5 g/ml and 46.5 g/ml respectively. About 95% to 100% growth inhibition of P. falciparum infected erythrocyte was observed when treated with TA164 and BSO at 16 g/ml and 64 g/ml respectively. The study on GSH contents indicated that non-infected erythrocytes treated with 6 g/ml (IC75 values) of TA164 at 24 hours incubation showed less GSH content as compared to non-treated erythrocytes. A similar observation was seen on treated trophozoite infected erythrocyte (10% parasitemia) when treated with 6 g/ml at 3 hours incubation. Analysis of the GSH contents of parasite compartments treated with TA164 at the same concentration (6 g/ml) for 3 hours incubation indicated a reduction of GSH contents. At the same concentration, TA164 did not affect the GSH contents of enriched trophozoite infected erythrocytes (60-70% parasitemia). TA164 did affect the GSH content of non-infected erythrocyte at 24 hours (accept IC50 value) as well as the parasite compartments (trophozoite infected erythrocyte and parasite itself) but fails to affect the GSH content of enriched trophozoite infected erythrocyte.
Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.
The effects of various fractions of Eurycoma longifolia Jack were studied on the orientation activities of the inbred, adult middle-aged Sprague-Dawley rats, 9 months old and retired breeders towards the receptive females (anogenital sniffing, licking, mounting), the environment (climbing, raring, exploration), themselves (nongenital grooming, genital grooming) and mobility (restricted, unrestricted) after treating these subjects twice daily for 10 days. Results showed that subjects treated with 800 mg/kg of E. longifolia Jack increased orientation activities towards the receptive females (anogenital sniffing, licking and mounting), increased genital grooming towards themselves and restricted movements to a particular area of the cage but decreased interest in the external environment (climbing, raring, exploration) as compared with the controls during the investigation period. In conclusion, this study gives further evidences that different fractions of E. longifolia Jack modified the orientation activities of the middle-aged male rats.
The effects of Eurycoma longifolia Jack were studied on the sexual qualities of middle aged male rats after dosing them with 0.5 g/kg of various fractions of E. longifolia whilst the control group received 3 ml/kg of normal saline daily for 12 weeks. Results showed than E. longifolia Jack enhanced the sexual qualities of the middle aged male rats by decreasing their hesitation time as compared to controls with various fractions of E. longifolia Jack produced 865-916 (91-96), 860-914 (92-98), 850-904 (93-99), 854-890 (95-99), 844-880 (94-98), 840-875 (94-98), 830-870 (94-98), 825-860 (94-98), 820-850 (96-99), 800-840 (93-98), 750-795 (94-99) and 650-754 sec (82-95%) in contrast to controls which produced 950 (100), 934 (100), 910 (100), 900 (100), 895 (100), 890 (100), 885 (100), 880 (100), 855 (100), 860 (100), 800 (100) and 790 sec (100%) throughout the investigation period. Besides these, there was a transient increase in the % of the male rats responding to the right choice after chronic administration of 0.5 g/kg E. longifolia Jack, with more than 50% of the male rats scored right choice after 2 weeks post-treatment and the effect was more prominent at the dose of the observation period. However, there was no sexual enhancement of the middle aged male rats which consumed normal saline since only 45-55% of the male rats responded to right choice throughout the investigation period. Hence, this study shows that E. longifolia Jack enhanced the sexual qualities of the middle aged male rats, further supports the folkuse of E. longifolia Jack as an aphrodisiac.
Eurycoma longifolia Jack was investigated for sexual motivation activity in adult, middle-aged male mice and in retired breeders, using the modified open field and the modified runway choice methods. Each mouse received 500 mg/kg of one of 4 fractions of E. longifolia Jack, viz. chloroform, methanol, butanol, and water, whereas the mice in the control and yohimbine groups received 3 ml/kg of normal saline and 30 mg/kg of yohimbine daily respectively for 10 d. The results show a transient increase in the percentage of male mice responding to the right choice after chronic consumption of the fractions with 50 percent of the adult middle-aged male mice treated with E. longifolia Jack and yohimbine scoring the right choice after 8 and 5 days post-treatment respectively. In conclusion, this study has shown that E. longifolia Jack continues to enhance sexual motivation in adult, middle-aged male mice and in retired breeders.
Eurycoma longifolia Jack commonly known as Tongkat Ali in Malaysia, has been used in Malaysia to increase male virility and sexual prowess. The objective of this study is to evaluate sexual arousal in sexually sluggish old male rats, 24 months old and retired breeders, receiving 200, 400, or 800 mg/kg of various fractions of E. longifolia Jack, twice daily, for 10 days. Control rats received 3 ml/kg of normal saline. The aphrodisiac effect was monitored by the act of yawning and stretching because yawning, either alone or associated with stretching, is considered an ancestral vestige surviving throughout evolution that promotes sexual arousal. The results showed that 800 mg/kg of E. longifolia Jack increased yawning by 50% and stretching by 16.7% in sexually sluggish old male rats, by 676-719% and 31-336%, respectively, in sexually active male rats, and by 22-44% and 75-100%, respectively, in middle aged, 9 months old and retired breeders. We conclude that the results of this study support the folk use of this plant as an aphrodisiac.
The effect of increasing doses of various fractions of Eurycoma longifolia Jack extracts on libido was examined in middle-aged male rats. The results showed that a high dose (800 mg/kg) of all E. longifolia Jack extracts significantly increased mount frequency (MF) (P < 0.05) over that of untreated controls, but had no effect on the frequency of intromission or ejaculation. Methanol, chloroform, water, and butanol fractions exhibited MF of 2.5 +/- 0.1, 2.6 +/- 0.3, 2.5 +/- 0.1 and 2.6 +/- 0.2, respectively, in adult, middle-aged male rats, and retired breeders versus 2.3 +/- 0.1 in untreated controls. This translated to a minor increase in MF of 8.7%, 13.0%, 8.7%, and 13.0% for these fractions, respectively, during the 20-minute observation period. The results of this study show that E. longifolia Jack extracts can increase libido in middle-aged male rats.
The methanol, n-butanol, chloroform and water extracts obtained from the root of Eurycoma longifolia Jack were assayed using methylene blue assay to evaluate its cytotoxic effect against KB, DU-145, RD, MCF-7, CaOV-3, MDBK cell lines. The results showed that all the root extracts except the water extract of E. longifolia produced significant cytotoxic effect on these cell lines. However, no significant cytotoxic effect was detected on MDBK (kidney) normal cell line. 9-methoxycanthin-6-one, an alkaloid, was detected in each extract with different intensities by reversed-phase high performance liquid chromatography.
The DCA (Drug Control Authority), Malaysia, has implemented the phase 3 registration of traditional medicines on 1 January 1992, with special emphasis on the quality, efficacy, and safety (including the presence of heavy metals) in all pharmaceutical dosage forms of traditional medicine preparations. As such, a total of 100 products in various pharmaceutical dosage forms of a herbal preparation, containing Tongkat Ali, were analyzed for mercury content using cold vapor atomic absorption spectrophotometer. Results showed that 36% of the above products possessed 0.52 to 5.30 ppm of mercury and, therefore, do not comply with the quality requirement for traditional medicines in Malaysia. Out of these 36 products, 5 products that possessed 1.05 to 4.41 ppm of mercury were in fact have already registered with the DCA, Malaysia. However, the rest of the products that contain 0.52 to 5.30 ppm of mercury still have not registered with the DCA, Malaysia. Although this study showed that only 64% of the products complied with the quality requirement for traditional medicines in Malaysia pertaining to mercury, they cannot be assumed safe from mercury contamination because of batch-to-batch inconsistency.
A validated HPLC analysis of eurycomanone (1), a bioactive quassinoid, in rat plasma following oral and intravenous administration of Eurycoma longifolia Jack extract was developed for pharmacokinetic and bioavailability studies. Relatively high plasma eurycomanone concentrations were detected after an intravenous injection of 10 mg/kg extract F2 containing 1.96 mg/kg of the quassinoid. However, it declined rapidly to zero after 8 h. Its mean elimination rate constant (k(e)), biological half-life (t(1/2)), volume of distribution (V(d)) and clearance (CL) were 0.88 +/- 0.19 h (-1), 1.00 +/- 0.26 h, 0.68 +/- 0.30 L/kg and 0.39 +/- 0.08 L/h/kg, respectively. Following oral administration of eurycomanone, its Cmax and Tmax values were detected as 0.33 +/- 0.03 microg/mL and 4.40 +/- 0.98 h, respectively. The plasma concentration of the quassinoid after oral administration was much lower than after intravenous application in spite of the oral dose being 5 times higher. The results indicate that eurycomanone is poorly bioavailable when given orally. A comparison of the AUC (0-->infinity) obtained orally to that obtained after an intravenous administration (normalized for dose differences) revealed that the absolute bioavailability of the compound was low with 10.5 %. Furthermore, the compound appeared to be well distributed in the extravascular fluids because of its relatively high V(d) value. The poor oral bioavailability was not attributed to instability problems because eurycomanone has been shown to be stable under different pH conditions. Thus, its poor oral bioavailability may be due to poor membrane permeability in view of its low P value and/or high first-pass metabolism.