Bioavailability of Eurycomanone in Its Pure Form and in a Standardised Eurycoma longifolia Water Extract

Ahmad, Norzahirah; Samiulla, Dodheri S.; Teh, Bee Ping; Zainol, Murizal; Zolkifli, Nor Azlina; Muhammad, Amirrudin; Matom, Emylyn; Zulkapli, Azlina; Abdullah, Noor Rain; Ismail, Zakiah; Mohamed, Ami Fazlin Syed

doi:10.3390/pharmaceutics10030090

Cited by 17 publications

(15 citation statements)

References 29 publications

(41 reference statements)

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“…Of the few publications on the repeated oral administration of tongkat ali extracts at 1000 mg/kg (aqueous extract), 2000 mg/kg (powdered root) and 2400 mg (aqueous extract) in rats, none reported any treatment-related mortality or clinical signs of toxicity [ 52 , 58 , 59 ]. A study on eurycomanone, which is a prominent chemical marker in E. longifolia , suggests that once it is absorbed in rodents, it is not easily metabolised and it can actively exert its pharmacological activities [ 65 ]. It is inferred that the low percentage of bioavailability, at approximately 11%, is unlikely to cause severe toxicity effects [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…A study on eurycomanone, which is a prominent chemical marker in E. longifolia , suggests that once it is absorbed in rodents, it is not easily metabolised and it can actively exert its pharmacological activities [ 65 ]. It is inferred that the low percentage of bioavailability, at approximately 11%, is unlikely to cause severe toxicity effects [ 65 , 66 ]. However, no steady state data are available to compare eurycomanone’s cumulative effect when administered in a repeated dose study of either the extract or the compound form.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Three important buckets belonging to quassinoids; 8.50 min – m/z 349.158 putatively identified as eurycomalactone (C 19 H 24 O 6 ) [24, 27], 7.71 min – m/z 409.142m/z putatively assigned as eurycomanone (C 20 H 24 O 9 ) [27] and 7.52 min – m/z 425.137 putatively identified as 13α-(21)-epoxyeurycomanone [24, 27] were detected. Eurycomanone is the most abundant phytochemical quassinoids in E. longifolia roots [24, 27 and 29] which has stable composition (not easily metabolized) [30]. A study by Low et al [31] reported that eurycomanone and 13α-(21)-epoxyeurycomanone possessed good physicochemical properties such as chemical stability, plasma stability, plasma protein binding, solubility and permeability.…”

Section: Resultsmentioning

confidence: 99%

LC-Based Metabolomics and Multivariate Analyses Reveal Metabolite Variations in Different Propagation Methods of Eurycoma longifolia Roots Harvested at Different Ages and Locations

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Basherudin

et al. 2020

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28Eurycoma longifolia is a well-known medicinal plant with pharmacological effects and 29 important bioactive compounds such as alkaloids and quassinoids. The suitable age of 30 harvesting E. longifolia root for commercial use is relatively unknown and could influence the 31 overall bioactive compounds present in the plant. In this study, non-targeted liquid 32 chromatography mass spectrometer (LC-MS) and multivariate analyses (MVA) were 33 performed to determine the chemical constituent of aqueous extract of 3-month-old E. 34 longifolia hairy root (HR) culture, 1-, 4-and 11-year-old harvested E. longifolia roots. 35 Unsupervised principle component analysis (PCA) and supervised partial least square 36 discriminant analysis (PLSDA) were applied to evaluate metabolic similarities and differences 37 in E. longifolia roots and hairy root in response to different harvesting age, locations and 38 propagation methods. A total of 34 significant buckets with variable importance in projection 39 (VIP) exceeding 1 were selected and identified. It was found that putatively identified 40 quassinoids were significantly higher in 1-, 4-and 11-year-old E. longifolia roots whereas 41 putative canthin-6-one alkaloids were abundantly present in 3-month-old E. longifolia hairy 42 root (HR). These findings may be applicable to improve the harvesting age and increase the 43 content of bioactive compounds in E. longifolia roots. 44 Introduction 54 Eurycoma longifolia Jack, locally known as Tongkat Ali, is an herbaceous tree of the family 55 Simaroubaceae, commonly found in Southeast Asian countries like Malaysia, Indonesia, 56 Thailand, Myanmar, Cambodia and Laos. E. longifolia, particularly its roots is traditionally 57 used for improvement of general health and libido. E. longifolia roots have been reported to 58 exhibit various pharmacological and biological activities such as antimicrobial [1-4], anti-59 diabetic [5], antimalarial [6, 7], aphrodisiac activities [8] and cytotoxicity against cancerous 60 cells [9-11]. The chemical profiling of E. longifolia root extract indicates alkaloids and 61 quassinoids derivatives as the major bioactive compounds found in this plant [12, 28]. 62 Quassinoids, particularly eurycomanone and their derivatives were reported to be abundant in 63 E. longifolia roots and responsible for various pharmacological properties. 64 The increasing demands of E. longifolia root as herbal medicinal products have been 65 impeded by the slow growth and late maturity of this plant. The suitable harvesting age of E. 66 longifolia roots is unclear, but for commercial use, E. longifolia roots are usually harvested at 67 the age of four years old [13]. Today, approximately 21,000 kg of E. longifolia were harvested 68 to meet a demand of more than 54,000 kg per year [12]. As a result, this practice has led to 69 excessive exploitation, extinction and adulterations in E. longifolia based products. Therefore, 70 there is a need to standardize harvesting age to ensure sufficient supply and sustainability of 71...

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“…Caffeine has been well studied and is reported to have a high tolerance dose of 400 mg/day in human [ 44 , 45 , 46 ]. Although eurycomanone has been reported to have low bioavailability in rats [ 47 , 48 ], its pharmacokinetic behavior may be modified when incorporated with coffee. A recent study reported coffee’s potential to alter acetaminophen drug pharmacokinetic profile when consumed together [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Eurycoma longifolia—Infused Coffee—An Oral Toxicity Study

et al. 2020

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Coffee infused with the additive Eurycomalongifolia, also known as Tongkat ali (TA), has become widely available in the Malaysian market. Safety evaluations for consumption of the products have been called for due to the herbal addition. This study investigates the acute, subacute and chronic effects of a commercial TA coffee in Sprague Dawley rats when given in a single, repeated and prolonged dosage. The dosages of 0.005, 0.05, 0.30 and 2 g/kg body weight (BW) were used in the acute study and 0.14, 0.29 and 1 g/kg BW were used in the repeated dose studies. The in-life parameters measured were food and water intake, body weight and clinical observations. Blood were collected for hematology and clinical biochemistry analyses. All animals were subjected to full necropsies. Non-toxicity-related changes were observed in the food and water consumption parameters. Body weight showed normal increments and none of the animals had any clinical signs of toxicity. Microscopically assessed organ tissues did not reveal any abnormalities. There was significant decrease of platelet count in all the chronic study male treated groups. Significant elevation of renal profile parameters in both gender groups given 0.29 g/kg BW, along with liver and lipid profile elevation in some female groups of the chronic study were noted. No dose-dependent relationship was apparent in the dosage range tested, though these changes may suggest an initial safety indication to the TA coffee. The study concludes that the no observed adverse effect level (NOAEL) for this commercial TA coffee was 1 g/kg BW.

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Bioavailability of Eurycomanone in Its Pure Form and in a Standardised Eurycoma longifolia Water Extract

Cited by 17 publications

References 29 publications

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

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

LC-Based Metabolomics and Multivariate Analyses Reveal Metabolite Variations in Different Propagation Methods of Eurycoma longifolia Roots Harvested at Different Ages and Locations

Eurycoma longifolia—Infused Coffee—An Oral Toxicity Study

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