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.
We attempted to investigate possible hepatoprotective effect of Eurycoma longifolia jack (ELJ) using carbon tetrachloride-induced (CC14) acute hepatotoxicity model in rats. Hepatotoxicity was induced by oral administration of 4.0mg/kg of CCI4 in corn oil (1:1) once to one experimental group of 5 rats and, in three other similar groups, challenged doses (300, 750 and 1500 mg/kg respectively) of ELJ were given one day before and one hour after 4.0 mg/kg CC14 and then once daily for three consecutive days. Three other groups of 5 rats each serving as controls were administered with distilled water, corn oil and ELJ (750mg/kg) only respectively. Rats were sacrificed on day three (corn oil & CC14 treated groups) and on day 4 (Distilled water, ELJ alone and CC14 with graded doses of ELJ treated groups) and samples of blood and liver tissue were taken for biochemical (serum) and histopathological examinations to assess hepatoprotection of ELJ against CC14-induced hepatotoxicity. In the low (300mg/kg) and medium (750 mg/kg) dose ELJ treated groups, CCI4 induced moderate inflammation, fatty acid change and necrosis of hepatocytes while in the high (1500mg/kg) dose ELJ, CC14 induced severe inflammation, fatty acid change and necrosis of hepatocytes. Biochemical measurements of ALT and ALP shows a moderate and insignificant reduction of serum levels in the low dose ELJ group but a more significant reduction in the medium and high dose ELJ groups when compared with the CC14 only group. The increase in serum total bilirubin caused by CC14 was non-significantly reduced by all the doses of ELJ. Animals treated with CC14 alone and in groups treated with both CC14 and graded doses of ELJ had a reduction in body weight, food and water intake but in ELJ (750mg/kg) only treated group, no such reduction in body weight, food and water intake was observed. This observation suggest that ELJ administered alone did not cause any toxic effect to the liver but in combination with CCI4, appeared to synergize the CC14-induced hepatotoxicity which increases as the dose of ELJ is increased. The anorexic, hypodypsic and reduced body weight evident in the CC14 alone and in ELJ plus CC14 treated groups but not in animals treated with ELJ alone, suggests that ELJ alone does not induce anorexia, hypodypsia or loss of weight. In conclusion, the results of our study suggest that ELJ is not hepatotoxic when given alone and appeared to have some degree of protective effects in rats against CC14-induced hepatotoxicity.
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.
An analytical method using HPLC with UV detection was developed to investigate the quassinoid content of Eurycoma longifolia Jack (Simaroubaceae) collected from various sources. Eurycomanone (1), longilactone (2), 14,15beta-dihydroxyklaineanone (3), 15beta-acetyl-14-hydroxyklaineanone (4), 6alpha-hydroxyeurycomalactone (5), and eurycomalactone (7) were isolated as reference standards and together with the synthesized 1beta,12alpha,15beta-triacetyleurycomanone (6, internal standard), were identified by NMR, MS, UV and IR spectroscopies. Their coefficient of variation values for 0.50-35 microg ml(-1) concentrations of quassinoids and their retention times measured within- and between-day were small. The recoveries of the spiked quassinoids in E. longifolia samples and their detection limits at 8.5 times signal to noise ratio were 99.75-109.13% and 0.01 microg ml(-1), respectively. From the root samples analysed, 1 had the highest concentration, being about 16.8-39.6 fold higher than the other quassinoids 2, 3, 5, 7 but 145.3 fold higher than 4 which showed the lowest concentration.
The roots of Eurycoma longifolia Jack have been used as traditional medicine to treat malaria. A systematic bioactivity-guided fractionation of this plant was conducted involving the determination of the effect of its various extracts and their chemical constituents on the lactate dehydrogenase activity of in vitro chloroquine-resistant Gombak A isolate and chloroquine-sensitive D10 strain of Plasmodium falciparum parasites. Their antiplasmodial activity was also compared with their known in vitro cytotoxicity against KB cells. Four quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (3), 13 alpha(21)-epoxyeurycomanone (4), eurycomalactone (6) and an alkaloid, 9-methoxycanthin-6-one (7), displayed higher antiplasmodial activity against Gombak A isolate but were less active against the D10 strain when compared with chloroquine. Amongst the compounds tested, 1 and 3 showed higher selectivity indices obtained for the cytotoxicity to antiplasmodial activity ratio than 14,15 beta-dihydroxyklaineanone (2), eurycomanol (5), 6 and 7.
This study investigated the effect of treatment with the proprietary standardized, water-soluble extract of the root of the Malaysian plant, Eurycoma longifolia Jack, which is thought to enhance male fertility with regard to higher semen volumes, sperm concentrations, the percentage of normal sperm morphology and sperm motility in male partners of sub-fertile couples with idiopathic infertility. A total of 350 patients were given 200 mg of the extract daily and follow-up semen analyses were performed every 3 months for 9 months. Of these 350 patients, 75 patients completed one full cycle of 3 months. Follow-up semen analyses in these patients showed significant improvement in all semen parameters. The proprietary extract of Eurycoma longifolia Jack significantly improved the sperm quality in these patients, allowing for 11 (14.7%) spontaneous pregnancies.
Medicinal plants have gained much interest in the prevention and treatment of common human disease such as cold and fever, hypertension and postpartum. Bioactive compounds from medicinal plants were synthesised using effective extraction methods which have important roles in the pharmaceutical product development. Orthosiphon aristatus (OA), Eurycoma longifolia (EL) and Andrographis paniculata (AP) are among popular medicinal herbs in Southeast Asia. The major compounds for these medicinal plants are polar bioactive compounds (rosmarinic acid, eurycomanone and andrographolide) which have multiple benefits to human health. The bioactive compounds are used as a drug to function against a variety of diseases with the support of scientific evidence. This paper was intended to prepare a complete review about the extraction techniques (e.g. OA, EL and AP) of these medicinal plants based on existing studies and scientific works. Suitable solvents and techniques to obtain their major bioactive compounds and their therapeutic potentials were discussed.
Microsatellite markers of an important medicinal plant, Eurycoma longifolia (Simaroubaceae), were developed for DNA profiling and genetic diversity studies.
Eurycoma longifolia Jack. is a treelet that grows in the forests of Southeast Asia and is widely used throughout the region because of its reported medicinal properties. Widespread harvesting of wild-grown trees has led to rapid thinning of natural populations, causing a potential decrease in genetic diversity among E. longifolia. Suitable genetic markers would be very useful for propagation and breeding programs to support conservation of this species, although no such markers currently exist. To meet this need, we have applied a genome complexity reduction strategy to identify a series of single nucleotide polymorphisms (SNPs) within the genomes of several E. longifolia accessions. We have found that the occurrence of these SNPs reflects the geographic origins of individual plants and can distinguish different natural populations. This work demonstrates the rapid development of molecular genetic markers in species for which little or no genomic sequence information is available. The SNP markers that we have developed in this study will also be useful for identifying genetic fingerprints that correlate with other properties of E. longifolia, such as high regenerability or the appearance of bioactive metabolites.
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.
The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age-depending decline in serum testosterone levels with concentrations being about 40-50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT.
F16 is a plant-derived pharmacologically active fraction extracted from Eurycoma longifolia Jack. Previously, we have reported that F16 inhibited the proliferation of MCF-7 human breast cancer cells by inducing apoptotic cell death while having some degree of cytoselectivity on a normal human breast cell line, MCF-10A. In this study, we attempted to further elucidate the mode of action of F16. We found that the intrinsic apoptotic pathway was invoked, with the reduction of Bcl-2 protein. Then, executioner caspase-7 was cleaved and activated in response to F16 treatment. Furthermore, apoptosis in the MCF- 7 cells was accompanied by the specific proteolytic cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Surprisingly, caspase-9 and p53 were unchanged with F16 treatment. We believe that the F16-induced apoptosis in MCF-7 cells occurs independently of caspase-9 and p53. Taken together, these results suggest that F16 from E. longifolia exerts anti-proliferative action and growth inhibition on MCF-7 cells through apoptosis induction and that it may have anticancer properties.
Blastocystis sp. infection, although many remain asymptomatic, there is growing data in recent studies that suggests it is a frequent cause of gastrointestinal symptoms in children and adults. This proposes that treatment against this infection is necessary however metronidazole (MTZ), which is the current choice of treatment, has expressed non-uniformity in its efficacy in combating this infection which has led to the study of alternative treatment. In our previous study, it was established that Tongkat Ali fractions exhibited promising anti-protozoal properties which leads to the current aim of the study, to further narrow down the purification process in order to identify the specific active compound promoting the anti-protozoal effect through HPLC analysis. Based on the data analysis and in-vitro susceptibility assay, the collected Tongkat Ali fraction that demonstrated anti-blastocystis property was shown to contain eurycomanone. Previous studies have suggested that there is a mechanism in Blastocystis sp. that regulates the apoptotic process to produce higher number of viable cells when treated. In reference to this, our current study also aims to investigate the apoptotic response of Tongkat Ali extract and eurycomanone across different subtype groups with comparison to MTZ. Based on our investigation, both Tongkat Ali extract and eurycomanone induced the high apoptotic rate however exhibited a reduction in viable cell count (p
This study aims to assess the effect of Eurycoma longifolia aqueous extract on chilled and cryopreserved quality of bull sperm. Semen samples were obtained from four Simmental-Brangus. Each sample was divided into two fractions: the first fraction was used for chilling the semen, and the second fraction was used for the freezing process. Both fractions were extended with Tris-egg yolk extender supplemented with 0.0, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mg/ml Eurycoma longifolia aqueous extract. The diluted chilled fraction was chilled at 5 °C for 6 days, whereas the frozen-thawed fraction was frozen in liquid nitrogen. Data revealed that 1 mg/ml E. longifolia aqueous extract yielded significantly (p
Introduction: Presently, the use of Eurycoma longifolia Jack (ELJ) (Tongkat Ali) has increased dramatically in Southeast Asia especially Malaysia where it is widely used as aphrodisiac and anti-malarial agent. Interestingly, its consumption has become popular in daily life as beverage to enhance energy and stamina especially among males. However, its effect on the safety of vital organs of the body has not been studied adequately. Hence, the main objective of this study was to determine whether or not long-term use of ELJ any has side effects on the liver in rats.
Methods: Three different concentrations of aqueous extract of ELJ were prepared and dissolved in distilled water. A total of 32 Sprague-Dawley male rats were used and randomly divided into three test groups and control. The test groups were given different doses (low dose 250 mg/kg bw, medium dose 500mg/kg bw and high dose 1000 mg/kg bw) of aqueous extract of ELJ, respectively. Control group was given distilled water alone. Doses were given orally and daily for 5 weeks. After 5 weeks, animals were sacrificed; whole liver tissues were obtained, fixed in 10 percent formaldehyde overnight for histological examination.
Result: Histological observations showed mild to moderate degrees of hemorrhage, hepatocytes degeneration and severe fatty changes in liver tissue of the test groups treated with ELJ as compared to control.
Conclusion: In conclusion, the long-term daily consumption of ELJ in large quantity as beverage may cause fatty changes, hemorrhage and hepatocytes degeneration in the liver tissue.
Eurycoma longifolia (E. longifolia), a herb commonly consumed for its aphrodisiac properties, is widely used by Asian males. This may include hypertensive patients receiving propranolol which may cause sexual dysfunction as one of its side-effects. There is no published study of the potential pharmacokinetic interaction between propranolol and the herb.
Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells. Interestingly, eurycomanone inhibited NF-κB signaling through inhibition of IκBα phosphorylation and upstream mitogen activated protein kinase (MAPK) signaling, but not eurycomanol. In conclusion, both quassinoids present differential toxicity towards leukemia cells, and the presence of the α,β-unsaturated ketone in eurycomanone could be prerequisite for the NF-κB inhibition.
Paracetamol (PCM) is a well-known drug widely used for its analgesic and antipyretic properties. PCM is generally considered as safe but overdose of PCM can cause nephrotoxicity. Traditionally, herbs have been used for the treatment of drug or toxin-induced renal disorders and numerous medicinal plants were tested for nephroprotection effect in PCM-induced nephrotoxicity model. The aim of the present study was to evaluate the protective effect of the herbal extract Eurycoma longifolia (EL) against PCM-induced nephrotoxicity rat model. Forty Wistar rats were randomly divided into five groups of eight rats each: control (vehicle 10 ml/kg), PCM alone (200 mg/kg PCM), EL 100 (EL 100 mg/kg+200 mg/kg PCM), EL 200 (EL 200 mg/kg+200 mg/kg PCM), and EL 400 (EL 400 mg/kg+200 mg/kg PCM). All animals from control group received vehicle daily and animals from groups PCM alone, EL 100, EL 200, and EL 400 received repeated dose of PCM and the assigned treatment of EL daily for a period of 14 days. On the 15th day, serum creatinine, blood urea nitrogen, protein, and albumin were measured in blood and creatinine clearance was measured in urine collected over 24 hours. Kidney sections of all experimental groups underwent histopathological analysis. There was a significant (p<0.05) increase in serum creatinine and blood urea levels in the PCM alone group compared to the treatment groups due to nephrotoxicity. In the treatment groups, there was a dose-dependent protection against PCM-induced changes observed in serum total protein, albumin, urea, and creatinine. Significant (p<0.05) drop was seen in serum creatinine and blood urea content in EL 200 and EL 400 groups. Creatinine clearance significantly increased for EL 200 (p<0.01) and EL 400 (p < 0.001) groups. Serum total protein and serum albumin content were significantly increased (p<0.05) in EL 200 and EL 400 groups compared to PCM alone group. Histopathological examination (H&E staining) of the rat kidneys revealed severe degeneration in the PCM alone group, while there was evidence of significant dose-dependent protection in the treatment groups against PCM-induced changes. The serum and urine biochemical results and histopathology analysis of the kidney indicate the nephroprotective potential of EL extract against PCM-induced nephrotoxicity.
There is little data concerning the ability of Eurycoma longifolia Jack (EL) to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats.
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.