Tongkat Ali (Eurycoma longifolia)

Testosterone boosters are heavily marketed on social media and marketplaces to men with claims to significantly increase testosterone. Lax industry regulation has allowed sales of supplements to thrive in the absence of verification of their purported benefits. Our primary objective was to systematically review all data published in the last two decades on testosterone boosters and determine their efficacy. Our outcome of interest was total testosterone increase versus placebo in four different populations: male athletes, men with late-onset hypogonadism infertile men and healthy men. Following search and screening, 52 studies were included in our review, relating to 27 proposed testosterone boosters: 10 studies of cholecalciferol; 5 zinc/magnesium; 4 Tribulus terrestris and creatine; 3 Eurycoma longifolia and Withania somnifera; 2 betaine, D-aspartic acid, Lepidium meyenii and isoflavones; while the remainder were single reports. Our findings indicate that most fail to increase total testosterone. The exceptions were β-hydroxy β-methylbutyrate and betaine, which can be considered effective for male athletes. Eurycoma longifolia, a blend of Punica granatum fruit rind and Theobroma cacao seed extracts (Tesnor™) and purified Shilajit extract (PrimaVie™) can be considered possibly effective for men with late-onset hypogonadism; Eurycoma longifolia and Withania somnifera possibly effective for healthy men; and a non-hormonal aromatase inhibitor (Novadex XT™) possibly effective for male athletes. © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Background and Objectives: Male hypogonadism is a clinical disorder characterized by reduced serum testosterone in men. Although treatment using herbal medicines, including Eurycoma longifolia, has been investigated, the benefits remain unclear. This study aims to investigate the efficacy of E. longifolia as a sole intervention to increase testosterone levels in males. Materials and Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the PRISMA guidelines. Relevant articles were retrieved from the databases PubMed, Scopus, Web of Science, Cochrane, Ovid/Embase, and Google Scholar. Results: After literature screening, a total of nine studies was included in the systematic review. Five RCTs were included in the meta-analysis. A significant improvement in total testosterone levels after E. longifolia treatment was mostly reported in both healthy volunteers and hypogonadal men. The random model effect revealed a significant increase (SMD = 1.352, 95% CI 0.565 to 2.138, p = 0.001) in the total testosterone levels in men receiving E. longifolia supplementation, which was confirmed in the hypogonadism subgroup. Conclusions: This systematic review and meta-analysis of the literature supports the possible use of E. longifolia supplementation for enhancing testosterone production. Although more research is required before its use in clinical practice, this may represent a safe and promising therapeutic option, particularly in hypogonadal men.

Eurycoma longifolia or Tongkat Ali (family: Simaroubaceae) has the potential to be utilised as an antimicrobial and antiparasitic agent that correlated with its traditional use to treat jaundice, malaria, antiseptic agent, and many more. This review is aimed at systematically sieving through articles regarding the antimicrobial and antiparasitic activity of E. longifolia. A total of 123 studies have been found using suitable keywords and manually searched from previous studies through the four databases. After title screening and abstract examination, 56 articles were excluded due to duplication and not meeting the acceptance criteria. 67 articles were assessed on full-text accessibility, 31 studies remained, and this number decreased to 20 articles after a careful examination of the full-text articles. Among the 20 articles selected, 17 articles proved the potential of E. longifolia as an antimicrobial and antiparasitic agent efficiently. 2 selected articles showed partial positive results, which specified specific microorganisms tested. In contrast, another 1 article gave a completely negative result. As for the conclusion, current studies highlighted by this review may shed light on the future direction of studies concerning E. longifolia as a novel antimicrobial and antiparasitic agent. However, more research should be done in the future focusing on the efficiency of E. longifolia for veterinary medicine utilisation.

The objective was to study available evidence for ingredients of popular over-the-counter testosterone and erectile dysfunction (ED) supplements. The top 16 male testosterone and 16 ED supplements in the USA were identified from the most popular online retailers: A1 Supplements, Amazon, Vitamin Shoppe, and Walmart. In total, 37 ingredients were identified and PUBMED online database was reviewed for randomized-controlled trials (RCT) studying their efficacy. Ingredients were categorized based on evidence quantity using an adapted version of the American Heart Association scoring system. In total, 16 ingredients from testosterone supplements and 21 from ED supplements were identified. Tribulus, Eurycoma longifolia, Zinc, L-arginine, Aspartate, Horny goat weed, and Yohimbine were most common. In all, 105 RCTs studying the identified ingredients were found. No whole supplement products have published RCT evidence. 19% of ingredients received an A grade for strong positive evidence with net positive evidence in two or more RCTs. In total, 68% received C or D grades for contradicting, negative, or lacking evidence. Overall, 69% of ingredients in testosterone supplements and 52% of ingredients in ED supplements have published RCT evidence. Many male supplements claim to improve testosterone or ED parameters; however, there is limited evidence, which should be considered when counseling patients.

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.

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.

An evidence-based systematic review of tongkat ali (Eurycoma longifolia) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

The prevalence of obesity in developing and developed countries has been well recognized, and the worldwide obesity rates have nearly tripled since 1975, according to the World Health Organization. CitruSlim, a standardized product containing a blend of Citrus bergamia and Eurycoma longifolia, can reduce cortisol, cholesterol, triglycerides, and hyperglycemia. These properties can contribute to reduction in body weight or body mass index (BMI) in obese patients. A randomized, double-blind, placebo-controlled clinical study was designed to evaluate the efficacy and tolerability of CitruSlim in body weight management in obese individuals, and the results were compared with that of placebo. A total of 97 participants were allocated, randomized, and treated with CitruSlim high-dose (HD, 400 mg), CitruSlim low-dose (LD, 200 mg), and placebo for 112 days. At the end of the study, CitruSlim HD and CitruSlim LD significantly reduced BMI compared to the placebo group and were well tolerated; however, it did not improve parameters associated with dyslipidemia and metabolic disturbances. The study findings suggested that CitruSlim was effective in reducing body weight in obese patients. © 2021 John Wiley & Sons Ltd.

Eurycoma longifolia supplementation increases testosterone levels in humans via activation of the hypothalamic-pituitary-gonadal axis and/or the hypothalamic-pituitary-adrenal axis mainly in older adults and nonhealthy populations. This study aimed to assess the impact of Eurycoma longifolia on the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes in healthy young males since this might promote functional testosterone prowess. Thirty-two males (24.4 ± 4.7 years; 1.74 ± 0.07 m; 73.7 ± 8.4 kg) in a placebo-controlled, double-blind, matched-paired study received 600 mg/day Eurycoma longifolia or placebo for two weeks. Blood analysis using repeated measures analysis of variance showed significant interaction and time effects for testosterone (F1,30 = 9.04, p = .005), free testosterone (F1,30 = 7.13, p = .012) and estradiol (F1,30 = 8.07, p = .008) levels in favour of the treatment group, while luteinising hormone, follicle-stimulating hormone and sexual hormone-binding globulin did not. The lack of changes in luteinising hormone and follicle-stimulating hormone levels suggests that a lesser role played by Eurycoma longifolia in activating the hypothalamic-pituitary-gonadal axis in the young adults. The raised testosterone level may be due to a greater rate of hormone production via the hypothalamic-pituitary-adrenal axis. The supplementation of Eurycoma longifolia for two weeks demonstrates steroidogenic effects on young men were dose-related. Consequently, the raised testosterone following Eurycoma longifolia supplementations could benefit muscle and strength gain in young adults. © 2021 Wiley-VCH GmbH.

BACKGROUND: Androgen deficiency of aging males (ADAM) largely manifests as sexual symptoms. Erectile dysfunction is one of the most common symptoms of ADAM. AIM: To ascertain the effect of concurrent training and supplementation with Eurycoma longifolia on erectile function and testosterone levels in men with ADAM, and the association of erectile function with levels of total testosterone. METHODS: 6-month, randomized, double-blind, placebo-controlled four-arm clinical. 45 men (47.38 ± 5.03 years) were randomized into 4 groups (G1: control + placebo; G2: control + Eurycoma longifolia; G3: concurrent training + placebo; G4: concurrent training + Eurycoma longifolia). 22 received a 200 mg supplement of Eurycoma longifolia and 23 underwent the intervention with concurrent training, 3 times a week for 60 min at progressive intensity. OUTCOMES: International Index of Erectile Function (IIEF-5), Aging Male Scale (AMS) and total testosterone. RESULTS: Erectile function demonstrated improvements in both interventions; however, the most significant results were obtained by men allocated to concurrent training + Eurycoma longifolia. CLINICAL IMPLICATIONS: A 200 mg supplement of Eurycoma longifolia and the practice of concurrent training for 6 months significantly improved the erectile function of men with ADAM. STRENGTHS & LIMITATIONS: The study's design stands out as a strength, in addition to the six-month intervention. The main limitation is the study not having groups that used only Eurycoma longifolia and only concurrent training. CONCLUSION: The combination of Eurycoma longifolia and concurrent training improved erectile function and increased total testosterone levels in men with ADAM. Exercise associated or not to the intake of Eurycoma longifolia improves strength and cardiorespiratory fitness in men with androgen deficiency. Leitão AE(1), Vieira MCS(2), Gomes DA(3), Boing L(4), Pelegrini A(5), Luiz E(6), Guimarães ACA(5). Author information: (1)Master's in Sciences of Human Movement of the Center of Sciences of the Health and of the Sport of the State University of Santa Catarina. Scholarship of the Coordination of Higher Education Personnel - CAPES, Brazil.

11. Complement Ther Clin Pract. 2021 Feb;42:101301. doi: 10.1016/j.ctcp.2020.101301. Epub 2021 Jan 5. Exercise associated or not to the intake of Eurycoma longifolia improves strength and cardiorespiratory fitness in men with androgen deficiency. Leitão AE(1), Vieira MCS(2), Gomes DA(3), Boing L

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 < 0.05). The numbers of total, naïve, and CD4(+) T cells were also higher in the TA group than those in P group (p < 0.05). No severe adverse events were observed. The results suggest that ingestion of the root water extract of TA (Physta®) enhances comprehensive immunity in both middle-aged men and women. This study is registered in UMIN-CTR (UMIN000011753).

WHAT IS KNOWN AND BACKGROUND: 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. OBJECTIVE: To study propranolol's pharmacokinetics when E. longifolia is consumed, comparing volunteers given either propranolol or a placebo. METHODS: This is a placebo-controlled randomized single-blinded crossover study of the effect of a water-based extract of E. longifolia on the pharmacokinetics of a single dose of proporanolol (Inderal(®)) in 14 healthy non-smoker young males. Eighty milligram of propranonol was orally administered with (i) placebo (Lactose) or (ii) 200 mg of water-based extract of E. longifolia (0·0272 ± 0·0026%eurycomanone) following an overnight fasting. Blood samples were collected at 0, 0·5, 1, 1·5, 2, 3, 4, 6, 8 and 10 h for propranolol's plasma concentration determinations using a validated high-performance liquid chromatography (HPLC) method. RESULTS AND DISCUSSION: When propranolol was administered with E. longifolia, its bioavailability (AUC0-∞) decreased by 29% while C(max) was reduced by 42% and T(max) was significantly prolonged by almost 86%. The terminal elimination half-life, however, was not significantly affected. CONCLUSION: The bioavailability of propranolol is significantly decreased when consumed together with E. longifolia. The interaction is due to a reduction in absorption, rather than an increase in propranolol's metabolism. Although the pharmacodynamics of propranolol was not affected in healthy volunteers, caution is still advisable with co-administration of the drug and the herb. © 2010 Blackwell Publishing Ltd.

With the global rise in aging populations and age-related diseases, the demand for safe and effective aging modulatory interventions is steadily increasing. Although several clinical drugs have shown aging modulatory potential, their long-term efficacy and safety remain major concerns. Plant-derived polysaccharides, known for their ability to modulate multiple longevity-related signaling pathways, have emerged as promising natural candidates due to their high biocompatibility and low toxicity. However, their underlying mechanisms remain insufficiently explored, limiting their translational potential. This study identified a novel aging modulatory intervention based on Eurycoma longifolia Jack polysaccharides (ELP) and systematically evaluated its effects in two established aging models, C. elegans and D. melanogaster. ELP significantly extended lifespan and healthspan in both models. Mechanistically, it reduced age-associated lipofuscin accumulation and polyglutamine aggregation, activated the conserved IIS/DAF-16 signaling pathway, and enhanced cellular defense by regulating antioxidant enzymes. Furthermore, metabolomic analysis revealed that ELP restored metabolic homeostasis by modulating key amino acid, carbohydrate, and lipid metabolic networks. Collectively, this study not only reveals a new natural aging modulatory intervention but also provides comprehensive mechanistic insights, supporting the future development of ELP as a safe and effective nutraceutical or therapeutic agent for mitigating age-related functional decline. © 2026. The Author(s), under exclusive licence to Springer Nature B.V.

Hyperuricemia (HUA) is a chronic metabolic disease which has been previously observed to be associated with cortisol metabolism disorders (pseudohypoadrenalism). In this study, we aimed to investigate the efficacy as well as mechanism of Eurycoma longifolia Jack (TkA) on alleviating cortisol metabolism. Oral administration of TkA significantly decreased serum uric acid levels and urinary cortisol in HUA mice. TkA improved HPA axis function and upregulated the levels of adrenal Hsd3b2, Cyp21a1 and Cyp11b1. In the liver, TkA upregulated the expression of Srd5a1 and Akr1c4, promoting the conversion from cortisol to 5α-tetrahydrocortisol (P < 0.001). TNFα was found to be the principal driver of reduced SRD5A1. By activating NF-κB pathway, recruited DNA methyltransferase (DNMT) binding with the CpG islands increased methylation level of Srd5a1. Our findings highlight that eurycomanol significantly inhibited the activation of IKKβ/IκBα/NF-κB/DNMT pathway as well as up-regulated hepatic SRD5A1, thereby restoring the systemic cortisol metabolic homeostasis under HUA.

BACKGROUND: Herbal supplements are increasingly used to manage menopausal symptoms. Physta® is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract, traditionally used for vitality. Its adaptogenic and anti-inflammatory properties promote hormonal balance, physical function, and sexual health, supporting its potential benefits for menopausal health. AIM: To investigate Physta®'s role in improving menopausal quality of life, mood states, and overall safety profile compared with placebo. METHODS: In this 12-week, randomized, double-blind, placebo-controlled trial, 138 females aged 40-55 with menopausal symptoms were randomly assigned to receive Physta® 50 mg, Physta® 100 mg, or placebo. MENQOL and POMS were assessed at baseline, week 6, and week 12. Safety outcomes were evaluated through biochemical tests, vital signs, and female reproductive hormonal profile. RESULTS: Physta® 100 mg significantly reduced total MENQOL scores by 33.9% from baseline to week 12 (P = 0.049) with notable improvements in the physical (-36.4%, P = 0.046) and sexual (-36.3%, P = 0.043) domains. Total mood disturbance also declined more in the Physta® 100 mg group (-38.6%) compared with placebo (-30.1%), although not statistically significant. No significant changes were observed in the vital signs and biochemical parameters, indicating the safety and tolerability of Physta®. No significant alterations were found in the female reproductive hormone profile, supporting its hormonal neutrality. CONCLUSION: Physta® 100 mg improved menopausal quality of life and mood without adverse effects, supporting its potential as a safe herbal therapy. Further studies with higher doses and longer durations are needed. ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.

Light quality significantly influences plant growth and development by interacting with photoreceptors, leading to reversible and irreversible outcomes. This study provides novel insights into the species-specific effects of light-emitting diodes (LEDs) on the morphological characteristics and genetic stability of Eurycoma longifolia hairy root cultures (ELHRCs) under different light qualities. LED treatments included white (400 nm-700 nm), blue (440 nm), mint green (530 nm), red (660 nm) and a combination of blue with red (1:1) (440 nm + 660 nm) applied for 8, 10 and 12 weeks. Morphological changes and growth were assessed alongside genetic stability through direct amplification of minisatellite DNA regions (DAMD) and inter-simple sequence repeat (ISSR) markers analysis using 12 primers. The results showed genetic similarity of 90.6% after 8 weeks and 100% after 10 and 12 weeks (DAMD) and 100%, 98.2% and 90.3% after 8, 10 and 12 weeks, respectively (ISSR) under all LED treatments, confirming the genetic stability of the hairy roots. Additionally, the study demonstrated how spectral quality influences hairy roots growth and morphology. The high percentage of genetic similarity highlights LEDs as a promising tool for in vitro culture of ELHRCs. These findings represent the first comprehensive report on the combined effects of LED spectral quality on growth, morphological changes and genetic stability in ELHRCs. Publisher: Kualiti cahaya secara signifikan mempengaruhi pertumbuhan dan perkembangan tumbuhan melalui interaksi dengan fotoreseptor, yang menghasilkan kesan boleh balik dan tidak boleh balik. Kajian ini memberikan perspektif baharu mengenai kesan spesifik spesies diod pemancar cahaya (LED) terhadap ciri morfologi dan kestabilan genetik kultur akar berbulu Eurycoma longifolia (ELHRCs) di bawah pelbagai kualiti cahaya. Rawatan LED yang digunakan termasuk putih (400 nm–700 nm), biru (440 nm), hijau pudina (530 nm), merah (660 nm) dan gabungan biru dan merah (1:1) (440 nm + 660 nm) yang diaplikasikan selama 8, 10 dan 12 minggu. Perubahan morfologi dan pertumbuhan dinilai bersama kestabilan genetik menggunakan analisis penanda penguatan langsung kawasan DNA m

We present the case of a 71-year-old gentleman who developed new-onset atrial flutter following the initiation of Tongkat Ali (Eurycoma longifolia) supplementation. He presented with a four-day history of palpitations and dizziness. Initial workup revealed normal laboratory values, including thyroid function and electrolytes. An electrocardiogram showed supraventricular tachycardia with a heart rate of 130 bpm, which, after adenosine administration, a clear atrial flutter. Secondary causes for atrial flutter were ruled out. Given the temporal association and the absence of other predisposing factors, his atrial flutter is presumed to be Tongkat Ali-induced, representing the first documented case in the literature. This case highlights the importance of considering herbal supplements as potential triggers for cardiac arrhythmias and underscores the need for increased awareness and further research into their cardiovascular safety profiles.

Background: Adaptogens, commonly used as traditional herbal medicinal products for the relief of symptoms of stress, such as fatigue and exhaustion, belong to a category of physiologically active compounds related to the physiological process of adaptability to stressors. They are used both as pharmaceuticals in medicine and as dietary supplements or nutraceuticals in nutrition, depending on the doses, indications to treat diseases, or support health functions. However, such a dual-faced nature of adaptogens can lead to inconsistencies and contradictory outcomes from Food and Drug regulatory authorities in various countries. Aims: This narrative literature review aimed to (i) specify five steps of pharmacological testing of adaptogens, (ii) identify the sources of inconsistencies in the assessment of evidence the safety, efficacy, and quality of multitarget adaptogenic botanicals, and (iii) propose potential solutions to address some food and drug regulatory issues, specifically adaptogenic botanicals used for prevention and treatment of complex etiology diseases including stress-induced, and aging-related disorders. Overview: This critically oriented narrative review is focused on (i) five steps of pharmacological testing of adaptogens are required in a sequential order, including appropriate in vivo and in vitro models in animals, in vitro model, and mechanisms of action by a proper biochemical assay and molecular biology technique in combination with network pharmacology analysis, and clinical trials in stress-induced and aging-related disorders; (ii) the differences between the requirements for the quality of pharmaceuticals and dietary supplements of botanical origin; (iii) progress, trends, pitfalls, and challenges in the adaptogens research; (iv) inadequate assignment of some plants to adaptogens, or insufficient scientific data in case of Eurycoma longifolia; (v) inconsistencies in botanical risk assessments in the case of Withania somnifera. Conclusions: This narrative review highlights the importance of harmonized standards, transparent methodologies, and a balanced, evidence-informed approach to ensure consumers receive effective and safe botanicals.

Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer that is often diagnosed at an advanced metastatic stage. The processes of cancer cell migration and invasion involve epithelial-to-mesenchymal transition (EMT), which is crucial for metastasis. Targeting cancer aggressiveness with effective plant compounds has gained attention as a potential adjuvant therapy. Eurycomanone (ECN), a bioactive quassinoid found in the root of Eurycoma longifolia Jack, has demonstrated anti-cancer activity against various carcinoma cell lines, including human NSCLC cells. This study aimed to investigate the in vitro effects of ECN on the migration and invasion of human NSCLC cells and to elucidate the mechanisms by which ECN modulates the EMT in these cells. Non-toxic doses (≤IC20) of ECN were determined using the MTT assay on two human NSCLC cell lines: A549 and Calu-1. The results from wound healing and transwell migration assays indicated that ECN significantly suppressed the migration of both TGF-β1-induced A549 and Calu-1 cells. ECN exhibited a strong anti-invasive effect, as its non-toxic doses significantly suppressed the TGF-β1-induced invasion of NSCLC cells through Matrigel and decreased the secretion of MMP-2 from these cancer cells. Furthermore, ECN could affect the TGF-β1-induced EMT process in various ways in NSCLC cells. In TGF-β1-induced A549 cells, ECN significantly restored the expression of E-cadherin by inhibiting the Akt signaling pathway. Conversely, in Calu-1, ECN reduced the aggressive phenotype by decreasing the expression of the mesenchymal protein N-cadherin and inhibiting the TGF-β1/Smad pathway. In conclusion, this study demonstrated the anti-invasive activity of eurycomanone from E. longifolia Jack in human NSCLC cells and provided insights into its mechanism of action by suppressing the effects of TGF-β1 signaling on the EMT program. These findings offer scientific evidence to support the potential of ECN as an alternative therapy for metastatic NSCLC.

Developing anti-gout medications that simultaneously reduce uric acid and exert anti-inflammatory effects represents a critical breakthrough for managing gout progression. Natural products with polypharmacological properties offer promising leads for drug discovery. In this study, β-carboline-1-propionic acid, a bioactive constituent of Eurycoma longifolia Jack, served as the starting point for drug design. Guided by a dual-target pharmacophore model, we design and synthesize 64 derivatives. Through systematic screening, 32 emerges as a drug candidate, demonstrating potent uric acid-lowering activity in male hyperuricemia mouse models (efficacy comparable to febuxostat and superior to lesinurad and benzbromarone) by inhibiting key urate transporters. In a male rat model of acute gouty arthritis, 32 mitigates NOD-like receptor protein 3 inflammasome-mediated inflammation. Notably, 32 exhibits enhanced safety compared to control drugs. This study exemplifies a natural product-inspired, dual-mechanism drug discovery approach, showcasing the potential of a rational polypharmacology and thus offering therapeutic opportunities for gout management. © 2025. The Author(s).

Eurycoma longifolia (also known as Tongkat Ali) is one of the valuable medicinal plants frequently used as traditional medicine in Malaysia. Its alkaloids and quassinoids reportedly confers antiparasitic activities. The effect of different Light Emitting Diode (LED) spectra treatments on E. longifolia hairy root cultures (ELHRCs) on alkaloid synthesis remains unexplored and its consequent antiparasitic effect on Blastocystis sp., a common intestinal protozoan parasite, is still unknown. In this study, the ELHRCs were irradiated to white, blue, red, blue plus red (1:1) and mint green LED illumination in vitro. The variation of alkaloids was assessed by using High-Performance Liquid Chromatography (HPLC) and employed to quantify 9-hydroxycanthin-6-one and 9-methoxycanthin-6-one. Subsequently, antiparasitic effect on Blastocystis sp. was assessed in in vitro parasite culture and the minimum inhibitory concentration (MIC90) was measured. Results showed the yields of high-value 9-hydroxycanthin-6-one in hairy roots increased by 1.17-fold, 2.74-fold, and 1.91-fold after 8, 10, and 12 weeks of culture under white, mint green, and blue lights relative to dark (control), respectively. In addition, 9-methoxycanthin-6-one yield in hairy roots increase by 1.07-fold and 1.34-fold after 8 and 12 weeks of culture under white light than in dark. Moreover, the ELHRCs crude extraction exhibited the highest anti-protozoal activity at 0.1 mg/ml against Blastocystis sp, ST3 compared to Metronidazole (MTZ). These results indicate that LED treatments alters alkaloid composition and are promising for obtaining higher yields of antiparasitic agents from the ELHRCs and thus can be considered a potential complementary and alternative antimicrobial agent. © 2025. The Author(s).

Eurycoma longifolia Jack, commonly known as Tongkat Ali, is a medicinal herb traditionally valued for its aphrodisiac properties, with eurycomanone being its principal bioactive quassinoid. This study introduces a novel, cost-effective method for the sensitive detection of eurycomanone using nitrogen-doped carbon quantum dots (N-CQDs) as a fluorescent probe. The spectral characteristics of the probe were carefully analyzed using UV-vis and fluorescence spectrophotometric techniques, and the sensing mechanism was investigated through Stern-Volmer and thermodynamic studies, revealing a static quenching interaction. A Box-Behnken design of experiment was applied to optimize the sensing conditions including pH, incubation time, and probe concentration, ensuring high sensitivity and robustness. A reduced quadratic model was found significant (p value > 0.0001) with pH and N-CQDs concentration being the most influential factors. The method was rigorously validated following ICH guidelines displaying excellent linearity in the range of 0.25-6.0 μg/mL, high sensitivity (LOD 0.067 μg/mL), and high accuracy and precision (RSD < 1.5%). The proposed technique was successfully applied to the analysis of real Tongkat Ali samples, demonstrating its practical utility in herbal analysis. The results showed good agreement with reported chromatographic methods, positioning the technique as a promising alternative to conventional analytical methods. © 2025 John Wiley & Sons Ltd.

Cryopreservation of rooster semen is essential for genetic conservation and breeding programs; however, the current methods result in a significant loss of viability. This study investigated the potential of Eurycoma longifolia (EL) extract and its cyclodextrin complex (EL-loaded cyclodextrin [ELC]) to improve rooster sperm cryopreservation. Supplementation with EL extract at 4 mg/mL significantly increased post-thaw total motility (62.84 ± 4.45 %), progressive motility (32.70 ± 2.48 %), viability (55.90 ± 0.72 %), and decreased MDA (2.98 ± 0.41 nmol/mL) compared to controls (P < 0.05). ELC (2 mg/mL) resulted in greater improvements in total motility (59.21± 1.03 %), progressive motility (38.46± 1.43 %), and viability (58.11± 0.58 %), and lower MDA levels (2.60 ± 0.04 nmol/mL) compared to control (P < 0.05). Both EL and ELC significantly improved fertility (55.38± 1.26 % and 52.19 ± 1.09 %, respectively; P < 0.05). These results highlight the potential of EL and ELC for optimizing cryopreservation protocols.

Cooled semen storage methods result in oxidative stress generated by an imbalance between oxidation rates, specifically reactive oxygen species production, and sperm cell antioxidants, leading to degradation of semen quality. We aimed to investigate the impact of adding Eurycoma longifolia (EL) extract as an antioxidant supplement in semen storage medium (IGGKPh semen extender) on semen quality and fertility potential. EL extract at concentrations of 5, 10, 15, and 20 mg/mL was assessed for its antioxidant capacity in IGGKPh semen extender. Our findings revealed that the total phenolic content in the EL extract did not vary significantly across the various concentrations and temperatures tested. However, incubation at 5°C was found to be the most effective temperature for increasing the EL extract antioxidant capacity as assessed via the 2,2-diphenyl-1-picrylhydrazyl inhibition assay in a dose-dependent manner. Supplementation of the IGGKPh semen extender with 15 mg/mL EL extract was found to enhance semen quality during cold storage for up to 48 h (p < 0.05), as evidenced by decreased malondialdehyde levels in cooled semen (p < 0.05). However, antioxidant enzyme activities showed no significant differences among the various experimental groups (p > 0.05). The fertility test showed that the 15 mg/mL EL extract group stored for 24 h had a higher percentage than the control group (p < 0.05). However, there was no significant difference in percentage between the two groups at 48 h of storage (p > 0.05). The hatchability showed no significant difference in both 24 and 48-h storage periods (p > 0.05). Our results indicated that supplementing the IGGKPh semen extender with 15 mg/mL EL extract may positively influence semen quality during storage, suggesting potential applications for enhancing semen quality.

Tongkat Ali (TA), also known as Eurycoma longifolia, has been used as a traditional herbal medicine for anti-aging, evidenced by clinical trials presenting the beneficial effects on energy, fatigue, and mood disturbance. We have recently shown that TA supplementation dose-dependently enhances the rest-activity pattern in C57BL/6 mice. Since destabilization of wakefulness and sleep is one of the typical symptoms of not only the elderly but also narcolepsy, we performed sleep analysis with and without dietary TA extract supplementation in middle-aged (10-12 months old) wild-type (WT) and narcoleptic DTA mice. We found that TA supplementation enhanced diurnal rhythms of locomotion and temperature in a time-of-day-dependent manner in WT mice but attenuated in DTA mice. In WT mice, TA supplementation consolidated wakefulness with a long bout duration and led to less entries into the sleep state during the active period, while it consolidated NREM sleep with long bout duration during the resting period. Neither disturbed sleep and wake cycles nor cataplexy was sufficiently improved in DTA mice. EEG spectral analysis revealed that TA supplementation enhanced slow wave activity (SWA) at both delta and low delta frequencies (0.5-4.0 and 0.5-2.0 Hz) during the light period, suggesting TA extract may induce vigilance during the active period, which then elicits a rebound effect during the resting period. Interestingly, DTA mice also slightly, but significantly, increased SWA at low frequencies during the light period. Taken together, our results suggest that TA supplementation enhances the Yin-Yang balance of sleep, temperature, and locomotion in WT mice, while its efficacy is limited in narcoleptic mice. © The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.

BACKGROUND AND AIM: In the livestock sector, particularly ruminants, an approach to minimize methane emissions can be carried out through a feeding strategy involving herbal plants containing bioactive compounds that can reduce protozoa and decrease methane gas emissions. The aim of this in vitro study was to analyze the effects of herbal plant supplementation on rumen fermentation, total gas, and methane production, in vitro dry matter digestibility (IVDMD), in vitro organic matter digestibility (IVOMD), and protozoa populations within the rumen. MATERIALS AND METHODS: Two experiments were conducted in this study. Experiment 1 was conducted to determine the most promising herbal plants capable of increasing total gas production and reducing protozoan populations. Three potential herbals selected in Experiment 1 were continued in Experiment 2 as supplements in the palm kernel meal (PKM)-based ration (70% PKM + 30% herbal plants). RESULTS: Experiment 1 revealed that Eurycoma longifolia (EL), Cola acuminata (CLA), and Cassia alata (CSA) were potential herbal candidates for enhancing total gas production and the percentages of IVDMD and IVOMD. In Experiment 2, supplementation with EL, CLA, and CSA significantly increased IVDMD from 62.84% to 70.15%, IVOMD from 61.61% to 53.18%, and NH3 from 13 mM to 17 mM, as well as reduced partial volatile fatty acids and total gas production. In addition, the methane gas and protozoan populations were reduced. CONCLUSION: The utilization of EL, CLA, and CSA effectively increased the production of total gas, IVDMD, and IVOMD while reducing methane gas protozoa populations in rumen fermentation compared with the control. Copyright: © Antonius, et al.

Drug-induced liver injury (DILI) presents a significant challenge in clinical practice, particularly with the rising popularity of herbal and dietary supplements (HDS) in the United States. Tongkat Ali (Eurycoma longifolia Jack), a Southeast Asian herb, has garnered attention for its purported health benefits, including enhancing testosterone levels. Here, we present a case of a 47-year-old male with acute liver injury following Tongkat Ali use, the first reported case of its kind in the literature. The patient exhibited worsening scleral icterus, elevated liver enzymes, and jaundice shortly after initiating Tongkat Ali supplementation, prompting hospitalization and subsequent clinical improvement upon discontinuation of the supplement. Differential diagnosis and exclusion of other etiologies were essential in establishing the causal link between Tongkat Ali consumption and liver damage, underscoring the difficulty in diagnosing HDS-induced liver injury. The rise in DILI cases parallels the expanding use of nutraceuticals, necessitating vigilance among healthcare professionals. While mechanisms of herbal-induced liver injury remain unclear, genetic predisposition and metabolic factors may be implicated. This case emphasizes the importance of heightened awareness among healthcare providers regarding the potential hepatotoxic effects of herbal supplements, particularly in individuals consuming multiple agents. Further research into the safety profile and mechanisms of Tongkat Ali-induced liver injury is warranted to inform clinical management and promote safer supplement use.

Eurycoma longifolia Jack (ELJ) is a herbal plant that has androgenic and antioxidant effects. We investigated the short-term effect of ELJ supplementation on muscle damage induced by eccentric exercise. Eighteen young (19-25 years), well-trained rugby 7s players were assigned to an ELJ or a placebo (PLA) group (n = 9/group). Each participant took four 100-mg capsules a day for seven days prior to performing a leg press eccentric exercise to failure in a double-blind fashion. Peak force, peak power and jump height in countermovement jump (CMJ), drop jump reactive strength index (RSI), muscle soreness assessed by a 100-mm visual analogue scale, plasma creatine kinase (CK) activity, and salivary hormones were measured at 24 h before and 0.5, 24, 48, 72, and 96 h after the exercise. Changes in the variables over time were compared between the groups by two-factor mixed-design ANOVA. The number of eccentric contractions performed was similar (P = 0.984) between the ELJ (21 ± 5) and PLA groups (21 ± 5). Salivary testosterone and cortisol concentrations did not change (P > 0.05) after the supplementation for both groups. CMJ peak power (-9.4 ± 5.6%) and height (-10.6 ± 4.9%), and RSI (-15.2 ± 16.2%) decreased at 24 h after exercise (P < 0.05), and muscle soreness (peak: 89 ±10 mm) and plasma CK activity (peak: 739 ± 420 IU/L) increased after exercise (P < 0.05) without significant differences between groups. These results showed that 7-day ELJ supplementation prior to the leg press eccentric exercise had no significant effects on hormones, performance and muscle damage markers for the athletes.

Eurycoma longifolia (Tongkat Ali; TA) is a traditional medicinal herb, commonly known as Malaysian ginseng. The root tea has been traditionally applied to treat fevers, aches, sexual dysfunction and other ailments. We evaluated the effects of TA extract supplementation on diurnal core body temperature (BT) and sleep architecture in model mice. Dietary supplementation with TA extract for 4 wk resulted in significantly and moderately reduced BT during the rest and active phases, respectively. A high dose delayed the onset of BT elevation at the start of the active phase, indicating that the effect was dose-dependent. Electroencephalography findings revealed that dietary supplementation with TA extract changed sleep rhythms and delta power during the inactive phase of NREM sleep, indicating improved sleep quality. Our findings suggested that dietary TA extract could be a promising natural aid that alleviates sleep problems via thermoregulation.