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Bioavailability and pharmacokinetic studies of eurycomanone from Eurycoma longifolia

Low BS, Ng BH, Choy WP, Yuen KH, Chan KL

Planta Med, 2005 Sep;71(9):803-7.
PMID: 16206032

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.

Matched MeSH terms: Eurycoma*
Sexual arousal in sexually sluggish old male rats after oral administration of Eurycoma longifolia Jack

Ang HH, Lee KL, Kiyoshi M

J Basic Clin Physiol Pharmacol, 2004;15(3-4):303-9.
PMID: 15803965 DOI: 10.1515/jbcpp.2004.15.3-4.303

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.

Matched MeSH terms: Eurycoma*
Fulltext Antibacterial activity of Eurycoma longifolia Jack. A Malaysian medicinal plant

Farouk AE, Benafri A

Saudi Med J, 2007 Sep;28(9):1422-4.
PMID: 17768473

Objective: To evaluate methanolic, ethanolic, acetone and aqueous extracts from different parts of Eurycoma longifolia (E. longifolia) (leave, stem, and root) for antibacterial activity against Gram-positive and Gram-negative bacteria and to utilize the leaves and stem parts rather than the root, which is already used for male sexual enhancement in Malaysia.

Methods: The study took place in the Laboratory of Molecular Biology of Biotechnology Engineering Department, Malaysia between January 2005 and June 2006. Methanolic, ethanolic, acetone and aqueous extracts of leaves, stems and roots of E. longifolia were investigated for their antibacterial properties using Agar-well diffusion method.

Results: The alcoholic and acetone extracts of the leaves and stem extracts were active on both Gram-positive and Gram-negative bacteria except against 2 strains of Gram-negative bacteria (Escherichia coli and Salmonella typhi). The root extracts had no antibacterial activity against Gram-positive and Gram-negative bacteria tested. Aqueous leaves extract showed antibacterial activity against Staphylococcus aureus and Serratia marscesens.

Conclusion: The alcoholic and acetone extracts from leaves and stems of E. longifolia contain potent antibacterial agent(s). This plant can serve as a potential source of antibacterial compounds.

Matched MeSH terms: Eurycoma*
Fulltext Effects of Eurycoma longifolia Jack standardised water extract (Physta) on well-being of perimenopausal and postmenopausal women: protocol for a randomised, double-blinded, placebo-controlled, parallel group study

Muniandy S, Yahya HM, Shahar S, Kamisan Atan I, Mahdy ZA, Rajab NF, et al.

BMJ Open, 2023 Nov 01;13(11):e073323.
PMID: 37914304 DOI: 10.1136/bmjopen-2023-073323

INTRODUCTION: Eurycoma longifolia Jack (EL), profoundly recognised as 'Tongkat Ali', is a medicinal herb originating from Southeast Asia. It is commonly used in traditional 'antiageing' treatments to address decreased energy, mood, libido and hormonal imbalances. While the benefits of EL have been extensively studied among the male population, less attention has been given to its effects on women. Menopause can impact the overall well-being of middle-aged women and incorporation of herbal supplements can aid them in managing the menopausal symptoms.
METHODS AND ANALYSIS: This 12-week randomised double-blind, placebo-controlled, parallel-group study aims to evaluate the efficacy of the standardised water extract of EL known as Physta in increasing the quality of life of perimenopausal and postmenopausal women. The study involves 150 women aged 40-55 years who score more than 61 on the Menopause-Specific Quality of Life (MENQOL) assessment. These participants will be randomised into three groups, receiving Physta at either 50 mg or 100 mg or a placebo. The outcomes measures include mood state, quality of life, fatigue, sleep quality, sexual function and pain score assessed using Profile of Mood State, MENQOL, Chalder Fatigue Scale, Pittsburgh Sleep Quality Index, Female Sexual Function Index and the Brief Pain Inventory questionnaires, respectively. The secondary outcome of the study includes full blood analysis, urine analysis, female reproductive hormone profiling, inflammatory and oxidative stress biomarkers analysis.
ETHICS AND DISSEMINATION: The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2021-898). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications.
TRIAL REGISTRATION NUMBER: ACTRN12622001341718.

Matched MeSH terms: Eurycoma*
Fulltext Tongkat Ali (Eurycoma longifolia): a possible therapeutic candidate against Blastocystis sp

Girish S, Kumar S, Aminudin N

Parasit Vectors, 2015;8:332.
PMID: 26082155 DOI: 10.1186/s13071-015-0942-y

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.

Matched MeSH terms: Eurycoma/chemistry*
Immunomodulation in Middle-Aged Humans Via the Ingestion of Physta® Standardized Root Water Extract of Eurycoma longifolia Jack--A Randomized, Double-Blind, Placebo-Controlled, Parallel Study

George A, Suzuki N, Abas AB, Mohri K, Utsuyama M, Hirokawa K, et al.

Phytother Res, 2016 Apr;30(4):627-35.
PMID: 26816234 DOI: 10.1002/ptr.5571

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

Matched MeSH terms: Eurycoma/chemistry*
Efficacy of Tongkat Ali (Eurycoma longifolia) on erectile function improvement: systematic review and meta-analysis of randomized controlled trials

Kotirum S, Ismail SB, Chaiyakunapruk N

Complement Ther Med, 2015 Oct;23(5):693-8.
PMID: 26365449 DOI: 10.1016/j.ctim.2015.07.009

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

Matched MeSH terms: Eurycoma/chemistry*
Fulltext Semen characteristics, extension, and cryopreservation of Rusa deer (Rusa timorensis)

Fitri WN, Wahid H, Rosnina Y, Jesse FFA, Aimi-Sarah ZA, Mohd-Azmi ML, et al.

Vet World, 2017 Jul;10(7):779-785.
PMID: 28831222 DOI: 10.14202/vetworld.2017.779-785

AIM: The objective of this research is to report parameters for breeding soundness evaluation, semen extension, and cryopreservation in Rusa timorensis.
MATERIALS AND METHODS: Seven healthy stags were chosen for semen collection using an electroejaculator. The collections were performed twice in a breeding season between February and June 2016. Samples were collected between 2 and 3 weeks interval, collected twice for each animal. Semen was evaluated, extended, and cryopreserved using four different extenders; Andromed®, BioXcell®, Triladyl®, and a modified Tris-egg yolk combined with Eurycoma longifolia Jack.
RESULTS: R. timorensis semen characteristics according to volume (ml), color, sperm concentration (106/ml), general motility (%), progressive motility (%), and % morphology of normal spermatozoa are 0.86±0.18 ml, thin milky to milky, 1194.2±346.1 106/ml, 82.9±2.8%, 76.1±4.8%, and 83.9±4.8%, respectively.
CONCLUSION: Semen characteristics of R. timorensis collected by electroejaculation is good allowing for cryopreservation and future artificial insemination work. The most suitable extender for Rusa deer semen is Andromed®.

Matched MeSH terms: Eurycoma
Fulltext Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers

Thu HE, Mohamed IN, Hussain Z, Shuid AN

J Ayurveda Integr Med, 2017 11 13;9(4):272-280.
PMID: 29146110 DOI: 10.1016/j.jaim.2017.04.005

BACKGROUND: Among the numerous well-documented medicinal herbs, Eurycoma longifolia (EL) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Though numerous animal studies have explored the bone-forming capacity of EL, the exact mechanism was yet to be explored.
OBJECTIVE(S): The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic model.
MATERIALS AND METHODS: The cell differentiation capacity of EL was investigated by evaluating cell growth, alkaline phosphatase (ALP) activity, collagen deposition and mineralization. Taken together, time-mannered expression of bone-related mediators which include bone morphogenic protein-2 (BMP-2), ALP, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-β1 (TGF-β1) and androgen receptor (AR) were measured to comprehend bone-forming mechanism of EL.
RESULTS: Results demonstrated a superior cell differentiation efficacy of EL (particularly at a dose of 25 μg/mL) that was evidenced by dramatically increased cell growth, higher ALP activity, collagen deposition and mineralization compared to the testosterone. Results analysis of the bone-related protein biomarkers indicated that the expression of these mediators was well-regulated in EL-treated cell cultures compared to the control groups. These findings revealed potential molecular mechanism of EL for the prevention and treatment of male osteoporosis.
CONCLUSION: The resulting data suggested that EL exhibited superior efficacy in stimulating bone formation via up-regulating the expression of various mitogenic proteins and thus can be considered as a potential natural alternative therapy for the treatment of osteoporosis.

Matched MeSH terms: Eurycoma
Fulltext Phytochemical properties and traditional uses of selected medicinal plants in Malaysia: a review

A’attiyyah A.A., Wan Afiqah Syahirah W.G., Kannan, T.P., Suharni M., Ahmad A., Nor Azah M.A.

Journal of Biomedical and Clinical Sciences, 2017;2(2):14-25.
MyJurnal

Medicinal plants have healing properties and are able to synthesize various chemical compounds. These chemicals (also known as phytochemical compounds) play vital roles in determining the pharmacological properties existing in certain plants. The phytochemical compounds present in plants are associated with primary and secondary constituents. Most of the time, the secondary constituents exhibit the bioactivities in plants such as antimicrobial, antioxidant, antidiabetic, antibacterial and anti-inflammatory properties. Some common medicinal plants that have been used in curing various diseases by traditional practitioners in Malaysia are Ficus deltoidea Jack, Andrographis paniculata, Curcuma longa, Clinacanthus nutans and Eurycoma longifolia Jack. This review discusses the morphology, phytochemical compounds and phytochemical properties of selected medicinal plants in Malaysia. The plants of focus have been found to possess anti-cancer and anti-diabetic effects. This review, it is hoped will enable Malaysian researchers to explore further on the potential of these plants in investigating new and novel drugs in the future.

Matched MeSH terms: Eurycoma
Fulltext Authenticity Testing and Detection of Eurycoma longifolia in Commercial Herbal Products Using Bar-High Resolution Melting Analysis

Fadzil NF, Wagiran A, Mohd Salleh F, Abdullah S, Mohd Izham NH

Genes (Basel), 2018 Aug 12;9(8).
PMID: 30103564 DOI: 10.3390/genes9080408

The present study demonstrated High Resolution Melting (HRM) analysis combined with DNA barcode (Bar-HRM) as a fast and highly sensitive technique for detecting adulterants in Eurycoma longifolia commercial herbal products. Targeting the DNA barcoding of the chloroplastic region-ribulose biphosphate carboxylase large chain (rbcL) and the nuclear ribosomal region- internal transcribed spacer 2 (ITS2), PCR amplification and HRM analysis using saturated Eva green dye as the source of fluorescence signals, was accomplished by employing a real-time cycler. The results were further validated by sequencing to identify unknown sequence from Genbank database and to generate phylogenetic tree using neighbour joint (NJ) analysis. Both of the DNA markers exhibited a distinguishable melting temperature and shape of the normalised curve between the reference and the adulterants. In the case of species identification, ITS2 was more successful in differentiating between species. Additionally, detection of admixture sample containing small traces of targeted E. longifolia DNA (w/v) can be detected as low as 5% for rbcL and less than 1% for ITS2, proving the sensitivity and versatility of the HRM analysis. In conclusion, the Bar-HRM analysis is a fast and reliable technique that can effectively detect adulterants in herbal products. Therefore, this will be beneficial for regulatory agencies in order to regulate food safety issues.

Matched MeSH terms: Eurycoma
Fulltext The Effect of Eurycoma Longifolia Jack (Tongkat Ali) on Carbon Tetrachloride -Induced Liver Damage in Rats

Al-Faqeh, H.H., Muhammad, B.Y., Nafie, E.M., Khorshid, A.

Malaysian Journal of Pharmaceutical Science, 2010;8(2):1-18.
MyJurnal

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.

Matched MeSH terms: Eurycoma
Fulltext Effect of long-term use of Eurycoma longifolia Jack on histopathological changes in the liver in rats

Hamoud HA

International Medical Journal Malaysia, 2014;13(2):29-33.
MyJurnal

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.

Matched MeSH terms: Eurycoma
Fulltext In vitro antibacterial activity of eurycoma longifolia jack (tongkat ali) root extract

Faisal, G.G., Zakaria, S.M., Najmuldeen, G.F.

International Medical Journal Malaysia, 2015;14(1):77-81.
MyJurnal

ntroduction: Currently, researchers are aiming to explore herbal plants to replace synthetic drugs because herbal plants contain high active compounds and fewer side effects. Our study was done to determine the antibacterial activity of Eurycoma longifolia Jack (E. longifolia) root using ethanol based extract. Methods: Five types of pathogenic bacterial strains were used; Gram-positive (Staphylococcus aureus and Bacillus ce- reus) and Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa). Disc diffusion assay and Minimum Inhibitory Concentration (MIC) tests were used to determine the inhibition zone and turbidity of suspension which reflects the antibacterial activity of the extract. Results: The ethanolic extract of E. longifolia Jack root extract showed positive results against Gram-positive bacteria (S. aureus and B. cereus) and Gram- negative (S. typhi). B.cereus and S.typhi showed inhibition zone values of 11.76mm and 14.33mm at the extract concentration of 150mg/ml that were higher than the positive control values (9.00, 12.67mm) respectively. However, E. coli and P. aeruginosa did not show any inhibition by the ethanol-based extract. Conclusion: From the results we can conclude that E.Longifolia root extract possesses antibacterial activity that can be further explored to produce new medicinal products.

Matched MeSH terms: Eurycoma
Fulltext A review on extraction techniques and therapeutic value of polar bioactives from Asian medicinal herbs: Case study on Orthosiphon aristatus, Eurycoma longifolia and Andrographis paniculata

Abd Aziz NA, Hasham R, Sarmidi MR, Suhaimi SH, Idris MKH

Saudi Pharm J, 2021 Feb;29(2):143-165.
PMID: 33679177 DOI: 10.1016/j.jsps.2020.12.016

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.

Matched MeSH terms: Eurycoma
Fulltext Herbal-Based Formulation Containing Eurycoma longifolia and Labisia pumila Aqueous Extracts: Safe for Consumption?

Teh BP, Ahmad N, Ibnu Rasid EN, Zolkifli NA, Sastu Zakaria UR, Mohamed Yusoff N, et al.

Pharmaceuticals (Basel), 2021 Feb 10;14(2).
PMID: 33579048 DOI: 10.3390/ph14020142

A combined polyherbal formulation containing tongkat ali (Eurycoma longifolia) and kacip fatimah (Labisia pumila) aqueous extracts was evaluated for its safety aspect. A repeated dose 28-day toxicity study using Wistar rats was conducted where the polyherbal formulation was administered at doses 125, 500 and 2000 mg/kg body weight to male and female treatment groups daily via oral gavage, with rats receiving only water as the control group. In-life parameters measured include monitoring of food and water consumption and clinical and functional observations. On day 29, blood was collected for haematological and biochemical analysis. The rats were necropsied and the organs were collected for histopathological examination. This study showed that the combined formulation did not induce any significant toxicity effect at any dose level in terms of morbidity, mortality, behaviour, functional observation, body weight, food and water consumption, whole blood haematology and serum biochemistry. However, there were some microscopic changes in the histopathological examinations of some organs given 2000 mg/kg body weight, which may suggest an early response to the polyherbal formulation. From this study, the no observed adverse effect level is estimated to be more than 500 mg/kg body weight but not exceeding 2000 mg/kg body weight. The observed effects at the highest dose indicate the need for further study of longer dosing duration.

Matched MeSH terms: Eurycoma
Fulltext Role of medicinal plants and natural products on osteoporotic fracture healing

Abd Jalil MA, Shuid AN, Muhammad N

Evid Based Complement Alternat Med, 2012;2012:714512.
PMID: 22973405 DOI: 10.1155/2012/714512

Popularly known as "the silent disease" since early symptoms are usually absent, osteoporosis causes progressive bone loss, which renders the bones susceptible to fractures. Bone fracture healing is a complex process consisting of four overlapping phases-hematoma formation, inflammation, repair, and remodeling. The traditional use of natural products in bone fractures means that phytochemicals can be developed as potential therapy for reducing fracture healing period. Located closely near the equator, Malaysia has one of the world's largest rainforests, which are homes to exotic herbs and medicinal plants. Eurycoma longifolia (Tongkat Ali), Labisia pumila (Kacip Fatimah), and Piper sarmentosum (Kaduk) are some examples of the popular ethnic herbs, which have been used in the Malay traditional medicine. This paper focuses on the use of natural products for treating fracture as a result of osteoporosis and expediting its healing.

Matched MeSH terms: Eurycoma
Fulltext Bone Micro-CT Assessments in an Orchidectomised Rat Model Supplemented with Eurycoma longifolia

Ramli R, Khamis MF, Shuid AN

Evid Based Complement Alternat Med, 2012;2012:501858.
PMID: 22952556 DOI: 10.1155/2012/501858

Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects of Eurycoma longifolia supplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model). Forty-eight-aged (10-12 months old) Sprague Dawley rats were divided into six groups of sham-operated (SHAM), orchidectomised control (ORX), orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised + Eurycoma longifolia 30 mg/kg (EL30), orchidectomised + Eurycoma longifolia 60 mg/kg (EL60), orchidectomised + Eurycoma longifolia 90 mg/kg (EL90). Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg) may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.

Matched MeSH terms: Eurycoma
Fulltext Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency

Mohd Effendy N, Mohamed N, Muhammad N, Naina Mohamad I, Shuid AN

Evid Based Complement Alternat Med, 2012;2012:125761.
PMID: 22844328 DOI: 10.1155/2012/125761

Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.

Matched MeSH terms: Eurycoma
Fulltext Combined Effects of Eurycoma longifolia and Testosterone on Androgen-Deficient Osteoporosis in a Male Rat Model

Saadiah Abdul Razak H, Shuid AN, Naina Mohamed I

Evid Based Complement Alternat Med, 2012;2012:872406.
PMID: 22924057 DOI: 10.1155/2012/872406

Androgen-deficient osteoporosis in men is treated with testosterone therapy, which is associated with side effects. Eurycoma longifolia (EL) is known to possess androgenic properties and has been reported to protect bone from androgen-deficient osteoporosis in experimental animal models. The present study aimed to determine the effectiveness of combination therapy of EL and testosterone (T) in treating androgen-deficient osteoporosis. Forty male Sprague-Dawley rats were divided into: sham-operated (SHAM), orchidectomized-control (ORX), orchidectomized with testosterone (ORX + T), orchidectomized with EL (ORX + EL), and orchidectomized with combined T and EL therapy (ORX + T + EL). EL was administered via oral gavages daily at the dose of 15 mg/kg. T was injected intramuscularly at 8 mg/kg and 4 mg/kg for the ORX + T and ORX + T + EL groups, respectively. Following 6 weeks of treatment, the osteocalcin levels of ORX + T and ORX + T + EL groups were significantly lower than the SHAM group (P < 0.05). The posttreatment CTX levels of ORX + T and ORX + T + EL groups were significantly lower than their pretreatment levels (P < 0.05). Biomechanically, the strain parameter of the ORX + T + EL group was significantly higher than the ORX group (P < 0.05). Thus, the combination therapy of EL and low-dose T has potential for treatment of androgen-deficient osteoporosis. The lower T dose is beneficial in reducing the sideeffects of testosterone therapy.

Matched MeSH terms: Eurycoma

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