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1.
Molecules ; 27(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35163852

RESUMO

An alkaloid compound from the hairy root culture of Eurycoma longifolia has been isolated and characterised as 9-methoxycanthin-6-one. The aims of these studies were to investigate the in vitro anti-cancer activities of 9-methoxycanthin-6-one against ovarian cancer (A2780, SKOV-3), breast cancer (MCF-7), colorectal cancer (HT29), skin cancer (A375) and cervical cancer (HeLa) cell lines by using a Sulphorhodamine B assay, and to evaluate the mechanisms of action of 9-methoxycanthin-6-one via the Hoechst 33342 assay and proteomics approach. The results had shown that 9-methoxycanthin-6-one gave IC50 values of 4.04 ± 0.36 µM, 5.80 ± 0.40 µM, 15.09 ± 0.99 µM, 3.79 ± 0.069 µM, 5.71 ± 0.20 µM and 4.30 ± 0.27 µM when tested in A2780, SKOV-3, MCF-7, HT-29, A375 and HeLa cell lines, respectively. It was found that 9-methoxycanthin-6-one induced apoptosis in a concentration dependent manner when analysed via the Hoechst 33342 assay. 9-methoxycanthine-6-one were found to affect the expressions of apoptotic-related proteins, that were proteins pyruvate kinase (PKM), annexin A2 (ANXA2), galectin 3 (LGAL3), heterogeneous nuclear ribonucleoprotein A1 (HNRNP1A1), peroxiredoxin 3 (PRDX3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the differential analysis of 2-DE profiles between treated and non-treated 9-methoxycanthine-6-one. Proteins such as acetyl-CoA acyltransferase 2 (ACAA2), aldehyde dehydrogenase 1 (ALDH1A1), capping protein (CAPG), eukaryotic translation elongation factor 1 (EEF1A1), malate dehydrogenase 2 (MDH2), purine nucleoside phosphorylase (PNP), and triosephosphate isomerase 1 (TPI1) were also identified to be associated with A2780 cell death induced by 9-methoxycanthine-6-one. These findings may provide a new insight on the mechanisms of action of 9-methoxycanthin-6-one in exerting its anti-cancer effects in vitro.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Eurycoma/química , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Apoptose , Proliferação de Células , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Células Tumorais Cultivadas
2.
Acta Chim Slov ; 68(4): 765-772, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34918749

RESUMO

Phytochemicals in the water extract of Eurycoma longofolia roots were identified using both solid-liquid and liquid-liquid extraction based fractionation techniques. A reversed phase C18 solid phase extraction (SPE) was used as solid-liquid extraction, whereas solvent partition was applied as liquid-liquid extraction. Total saponin was increased after fractionation. A few known quassinoids; eurycomanone, 13a(21)-epoxyeurycomanone, pasakbumin D, 13ß,18-dihydroeurycomanol and 13ß,21-dihydroxyeurycomanol were identified from the 40% and 60% methanol fractions of SPE. Solvent partition extract using ethyl acetate was found to have the highest saponin content compared to butanol and chloroform fractions. Subsequent acetone precipitation of the organic fractions recovered a formylated hexose trimer and other saccharide-containing compounds. Ethyl acetate effectively recovered saponins from E. longofolia water extract using liquid-liquid extraction followed by acetone precipitation.


Assuntos
Eurycoma/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Eurycoma/metabolismo , Extração Líquido-Líquido , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Quassinas/análise , Quassinas/isolamento & purificação , Extração em Fase Sólida , Solventes/química , Espectrometria de Massas em Tandem , Água/química
3.
Molecules ; 26(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34641483

RESUMO

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Eurycoma/química , Leucemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Quassinas/farmacologia , Proliferação de Células , Células HL-60 , Humanos , Células K562 , Leucemia/patologia
4.
Sci Rep ; 11(1): 7833, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837230

RESUMO

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 < 0.05) when compared to MTZ. This study suggests that there is potential in developing a standardized treatment regardless of subtype variations which makes Tongkat Ali extract a promising anti-protozoal treatment against all Blastocystis sp. subtype groups.


Assuntos
Antiprotozoários/farmacologia , Apoptose/efeitos dos fármacos , Infecções por Blastocystis/parasitologia , Blastocystis/efeitos dos fármacos , Eurycoma/química , Metronidazol/farmacologia , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Blastocystis/isolamento & purificação , Blastocystis/metabolismo , Descoberta de Drogas/métodos , Humanos , Testes de Sensibilidade Microbiana
5.
Nutrients ; 13(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918334

RESUMO

Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.


Assuntos
Anabolizantes/farmacologia , Suplementos Nutricionais , Magnoliopsida/química , Condicionamento Físico Animal/fisiologia , Extratos Vegetais/farmacologia , Adiposidade/efeitos dos fármacos , Ajuga/química , Animais , Modelos Animais de Doenças , Eurycoma/química , Feminino , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Orquiectomia , Ovariectomia , Sarcopenia/etiologia , Sarcopenia/prevenção & controle , Urtica dioica/química
6.
J Chromatogr Sci ; 59(7): 659-669, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876232

RESUMO

The objective of the study was to fractionate the crude extract of Eurycoma longifolia (E. longifolia) roots and identify the intense peaks using HPLC-PDA-MS/MS, UPLC-MS/MS and H-NMR. Column chromatography was used to fractionate the crude extract into individual fractions using six solvent systems ranged from ethyl acetate, methanol and water in increasing polarity. Two fractions with nearly pure and intense peaks were selected for compound identification. Chromenone (coumarin) and chromone derivatives were putatively identified, besides several previously reported quassinoid glycosides (eurycomanone derived glycoside, 2,3-dehydro-4α-hydroxylongilactone glucoside, eurycomanol glycoside and eurycomanol trimer) in the fraction 11 of 100% methanol. A newly reported compound, namely hydroxyl glyyunanprosapogenin D (838 g/mol) was proposed to be the compound detected in the fraction 11 of 50% ethyl acetate and 50% methanol. This is also the first study to report the identification of chromenones and chromones in E. longifolia extract.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Eurycoma/química , Compostos Fitoquímicos , Raízes de Plantas/química , Espectrometria de Massas em Tandem/métodos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Extratos Vegetais/química
7.
J Proteome Res ; 20(5): 2714-2724, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33856806

RESUMO

The metabolic and bioactivity effects of Eurycoma longifolia (Eucalyptus longifolia) in obesity treatment were studied in mice fed with a high-fat diet using a metabolomics approach. Aqueous extracts of E. longifolia were obtained via grinding, dissolving, and freeze-drying. The hepatic steatosis effect of E. longifolia was characterized by hematoxylin and eosin histological staining. External performance of the obesity-alleviation effect was monitored by measuring body and food weight. In addition, the metabolomics analysis of the E. longifolia-mice interaction system was performed using the established platform combining liquid chromatography-tandem mass spectrometry with statistical analysis. The presence and spatial distribution patterns of differential molecules were further evaluated through desorption electrospray ionization-mass spectrometry imaging. The results showed that E. longifolia played a vital role in downregulating lipid accumulation (especially triacylglycerols) and fatty acids biosynthesis together with enhanced lipid decomposition and healing in Bagg albino mice. During such a process, E. longifolia mainly induced metabolomic alterations of amino acids, organic acids, phospholipids, and glycerolipids. Moreover, under the experimental concentrations, E. longifolia induced more fluctuations of aqueous-soluble metabolites in the plasma and lipids in the liver than in the kidneys. This study provides an advanced alternative to traditional E. longifolia-based studies for evaluating the metabolic effects and bioactivity of E. longifolia through metabolomics technology, revealing potential technological improvement and clinical application.


Assuntos
Eurycoma , Animais , Dieta Hiperlipídica/efeitos adversos , Lipídeos , Metabolômica , Camundongos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia
8.
J Pharm Pharmacol ; 73(2): 161-168, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33793798

RESUMO

OBJECTIVES: The quassinoids eurycomanone (EN) and 13α,21-dihydroeurycomanone (DHY) of Eurycoma longifolia Jack are reported to enhance spermatogenesis. This study aims to profile the pharmacokinetics of DHY, a minor and hitherto unstudied constituent, evaluate its spermatogenesis enhancement property and compare these attributes with that of the predominant EN. METHODS: Crude Eurycoma longifolia extract was chromatographed into a DHY-enriched extract (DHY-F) and an EN-enriched extract (EN-F). Male Sprague-Dawley rats were administered intravenously and orally with both extracts and their plasma levels of both quassinoids were determined. The extracts were then tested for their spermatogenesis augmentation ability in normal rats and an andrographolide-induced oligospermia model. KEY FINDINGS: Chromatographic enrichment resulted in a 28-fold increase of DHY in DHY-F and a 5-fold increase of EN in EN-F compared with non-chromatographed crude extracts. DHY showed better oral bioavailability (1.04 ± 0.58%) than EN (0.31 ± 0.19%). At 5 mg/kg, EN exhibited higher efficacy in spermatogenesis enhancement in normal rats and restoration of oligospermia to normal sperm profile versus DHY. CONCLUSIONS: Despite the better pharmacokinetic profile of DHY, EN remains the main chemical contributor to plant bioactivity. DHY-F and EN-F represent improvements in developing Eurycoma longifolia as a potential phytomedicine for male infertility particularly oligospermia.


Assuntos
Eurycoma/química , Oligospermia/tratamento farmacológico , Extratos Vegetais/farmacocinética , Quassinas/farmacocinética , Espermatogênese/efeitos dos fármacos , Administração Oral , Animais , Disponibilidade Biológica , Diterpenos , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Quassinas/isolamento & purificação , Quassinas/farmacologia , Ratos , Ratos Sprague-Dawley
9.
Maturitas ; 145: 78-85, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33541567

RESUMO

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.


Assuntos
Disfunção Erétil/terapia , Eurycoma , Exercício Físico , Extratos Vegetais/uso terapêutico , Adulto , Envelhecimento/sangue , Envelhecimento/fisiologia , Androgênios/sangue , Androgênios/deficiência , Método Duplo-Cego , Disfunção Erétil/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Testosterona/sangue , Testosterona/deficiência
10.
Andrologia ; 53(4): e14001, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33559971

RESUMO

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.


Assuntos
Eurycoma , Idoso , Método Duplo-Cego , Humanos , Sistema Hipotálamo-Hipofisário , Masculino , Sistema Hipófise-Suprarrenal , Extratos Vegetais/farmacologia , Testosterona , Adulto Jovem
11.
Complement Ther Clin Pract ; 42: 101301, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33445146

RESUMO

This study aims to analyze the effects of a concurrent training (CT) associated with Eurycoma longifolia (EL) supplementation on the muscle strength, cardiorespiratory fitness, and symptomatology score of men with the androgen deficiency of aging male (ADAM). Forty-five subjects (47.6 ± 5.2 years) were included in the study. The randomized, double-blinded, placebo controlled clinical trial lasted for 6 months. Participants were randomized into four groups, control (C; n = 12); EL (n = 11); CT (n = 11); and CT + EL (n = 11). Along this period, the isokinetic peak torque of the knee extensors increased in the CT (14%) and CT + EL (17%) groups (p = 0.040; p = 0.006, respectively), while the isokinetic peak torque of knee flexion increased in the CT + EL group only (p < 0.05). For all participants, testosterone levels were correlated with isokinetic peak torque of knee extension (r = 0.517, p = 0.001) and flexion (r = 0.362, p = 0.028). Subjects of the CT (27.3%) and CT + EL (36.1%) groups decreased the symptomatology of ADAM (p = 0.005). This study demonstrated the benefits of CT and EL consumption as a non-pharmacological treatment for ADAM.


Assuntos
Aptidão Cardiorrespiratória , Eurycoma , Androgênios , Exercício Físico , Humanos , Masculino , Força Muscular , Músculo Esquelético
12.
J AOAC Int ; 104(3): 802-810, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-33064798

RESUMO

BACKGROUND: Quassinoids and canthin-6-one alkaloids are bioactive markers of Eurycoma longifolia (EL) and E. harmandiana (EH) and have been commercially utilized to treat inflammation and male infertility. OBJECTIVES: This study aims to reveal the contents of bioactive compounds and compare anti-inflammatory activities of these two species. METHODS: HPLC methods coupled with UV-Vis detection were developed and validated for the simultaneous analysis of the chemical profiles and their contents in EL and EH. The anti-inflammatory activities of both species were investigated using RAW 264.7 cell line. RESULTS: The HPLC methods provided a sensitivity (LOD) of 0.02-0.05 µg/mL for the eight bioactive compounds (canthin-6-one alkaloids, quassinoids, and scopoletin) with high precision (% relative standard deviation (RSD) ≤6.48) and recoveries between 80.0 and 120%. The chaparrinone: eurycomanone ratio was high in EH, whereas EL had a higher ratio of eurycomanone: chaparrinone than EH. The contents of total canthin-6-one alkaloids, quassinoids, and scopoletin were 0.01-0.75, 0.19-1.54, and 0.01-0.28 mg/g, respectively, in EL roots and 0.12-1.80, 7.05-9.26, and 0.02 mg/g, respectively, in EH roots. The anti-inflammatory effects of EL and EH extracts varied among the samples due to the variation in their chemical constituents. CONCLUSIONS: In summary, our study indicated that chaparrinone was the major compound in EH. EH exhibited anti-inflammatory activity to the same extent as EL. HIGHLIGHTS: EH and EL extracts were analyzed using developed HPLC-UV methods, revealing a high concentration of chaparrinone in EH, and an anti-inflammatory assay indicated that EH had a potency comparable to that of EL.


Assuntos
Alcaloides , Eurycoma , Quassinas , Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Carbolinas , Cromatografia Líquida de Alta Pressão , Humanos , Alcaloides Indólicos , Masculino , Extratos Vegetais/farmacologia , Raízes de Plantas , Quassinas/farmacologia , Escopoletina
13.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6435-6446, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34994136

RESUMO

A sensitive and efficient method was established and validated for qualitative and quantitative analysis of total alkaloids from the extract of Eurycoma longifolia by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS) combined with ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS). The HPLC-Q-TOF-MS conditions are as follows: Welch Ultimate XB-C_(18) column(4.6 mm×250 mm, 5 µm) with acetonitrile(containing 0.1% formic acid)-0.1% formic acid in water as mobile phase for gradient elution. The UPLC-QQQ-MS/MS conditions are as below: Agilent Eclipse Plus C_(18) column(2.1 mm×50 mm, 1.8 µm) with acetonitrile(containing 0.1% formic acid) and 0.1% formic acid in water as mobile phase for gradient elution. MS data were collected by electrospray ionization in positive ion mode. According to the comparison with reference standards and the accurate masses of molecules, a total of 17 alkaloids in E. longifolia extract were identified by HPLC-Q-TOF-MS. The UPLC-QQQ-MS/MS quantitative analysis result of 3 alkaloids showed that the linear ranges of them were good(r≥0.999 7) and the overall recoveries ranged from 108.8%-110.2%, with RSDs of 2.9%-5.3%. The method is accurate, reliable, and efficient, which can comprehensively reflect the constituents and content of alkaloids in E. longifolia. The result can serve as a reference for further elucidating its therapeutic material basis and quality control.


Assuntos
Alcaloides , Eurycoma , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Espectrometria de Massas em Tandem
14.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4667-4676, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164431

RESUMO

In this work, a sensitive and efficient method was established and validated for qualitative and quantitative analysis of major quassinoid diterpenoids constituents from the extract of Eurycoma longifolia by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS). The UPLC-Q-TOF-MS analysis was performed on an Agilent Eclipse Plus C_(18) RRHD(2.1 mm×100 mm,1.8 µm) column with acetonitrile and 0.1% formic acid water as mobile phase by gradient elution. The UPLC-QQQ-MS/MS analysis was performed on an Agilent Eclipse Plus C_(18) RRHD(2.1 mm×50 mm, 1.8 µm)column with acetonitrile and 0.1% formic acid water as mobile phase by gradient elution. The data was collected by electrospray ionization in positive mode. According to the contrast of the reference standards and the accurate masses of molecules, a total of 32 quassinoid diterpenoids in E. longifolia extract were identified by UPLC-Q-TOF-MS. For quantitative the linear range of 4 detected quassinoid diterpenoids were good(r≥0.999 6), and the overall recoveries ranged from 90.35% to 106.4%, with the RSD ranging from 1.8% to 3.6%. The method was accurate, reliable and efficient, and could comprehensively reflect the chemical constituents and content of E. longifolia, and could provide a reference for further elucidating its pharmacological basis and quality control.


Assuntos
Medicamentos de Ervas Chinesas , Eurycoma , Quassinas , Cromatografia Líquida de Alta Pressão , Diterpenos , Espectrometria de Massas em Tandem
15.
Nutrients ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066137

RESUMO

Coffee infused with the additive Eurycoma longifolia, 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.


Assuntos
Coffea/toxicidade , Eurycoma/química , Aditivos Alimentares/toxicidade , Nível de Efeito Adverso não Observado , Extratos Vegetais/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Coffea/química , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Eurycoma/efeitos adversos , Feminino , Aditivos Alimentares/administração & dosagem , Aditivos Alimentares/isolamento & purificação , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Contagem de Plaquetas , Ratos Sprague-Dawley , Caracteres Sexuais
16.
Oncol Rep ; 44(4): 1441-1454, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945500

RESUMO

The high activation of protein kinase B (AKT)/nuclear factor­κB (NF­κB) signaling has often been associated with the induction of non­small cell lung cancer (NSCLC) cell survival and resistance to cisplatin, which is one of the most widely used chemotherapeutic drugs in the treatment of NSCLC. The inhibition of AKT/NF­κB can potentially be used as a molecular target for cancer therapy. Eurycomalactone (ECL), a quassinoid from Eurycoma longifolia Jack, has previously been revealed to exhibit strong cytotoxic activity against the human NSCLC A549 cell line, and can inhibit NF­κB activity in TNF­α­activated 293 cells stably transfected with an NF­κB luciferase reporter. The present study was the first to investigate whether ECL inhibits the activation of AKT/NF­κB signaling, induces apoptosis and enhances chemosensitivity to cisplatin in human NSCLC cells. The anticancer activity of ECL was evaluated in two NSCLC cell lines, A549 and Calu­1. ECL decreased the viability and colony formation ability of both cell lines by inducing cell cycle arrest and apoptosis through the activation of pro­apoptotic caspase­3 and poly (ADP­ribose) polymerase, as well as the reduction of anti­apoptotic proteins Bcl­xL and survivin. In addition, ECL treatment suppressed the levels of AKT (phospho Ser473) and NF­κB (phospho Ser536). Notably, ECL significantly enhanced cisplatin sensitivity in both assessed NSCLC cell lines. The combination treatment of cisplatin and ECL promoted cell apoptosis more effectively than cisplatin alone, as revealed by the increased cleaved caspase­3, but decreased Bcl­xL and survivin levels. Exposure to cisplatin alone induced the levels of phosphorylated­AKT and phosphorylated­NF­κB, whereas co­treatment with ECL inhibited the cisplatin­induced phosphorylation of AKT and NF­κB, leading to an increased sensitization effect on cisplatin­induced apoptosis. In conclusion, ECL exhibited an anticancer effect and sensitized NSCLC cells to cisplatin through the inactivation of AKT/NF­κB signaling. This finding provides a rationale for the combined use of chemotherapy drugs with ECL to improve their efficacy in NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Eurycoma/química , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-akt/genética , Células A549 , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/efeitos adversos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lactonas/química , Lactonas/farmacologia , Transdução de Sinais/efeitos dos fármacos
17.
Mol Med Rep ; 22(5): 3645-3658, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32901880

RESUMO

Eurycoma (E.) longifolia Jack (Tongkat Ali) is a widely applied medicine that has been reported to boost serum testosterone and increase muscle mass. However, its actual biological targets and effects on an in vitro level remain poorly understood. Therefore, the present study aimed to investigate the effects of a standardised E. longifolia extract (F2) on the growth and its associated gene expression profile in mouse Leydig cells. F2, even at lower doses, was found to induce a high level of testosterone by ELISA. The level was as high as the levels induced by eurycomanone and formestane in Leydig cells. However, Leydig cells treated with F2 demonstrated reduced viability, which was likely due to the diminished cell population at the G0/G1 phase and increased cell population arrested at the S phase in the cell cycle, as assessed by MTT assay and flow cytometry, respectively. Cell viability was revived when the treatment time­point was prolonged to 96 h. Genome­wide gene analysis by reverse transcription­quantitative PCR of F2­treated Leydig cells at 72 h, when the cell growth was not revived, and 96 h, when the cell growth had started to revive, revealed cyclin­dependent kinase­like 2 (CDKL2) to be a potential target in regulating the viability of F2­treated Leydig cells. Functional analysis, as analysed using GeneMANIA Cytoscape program v.3.6.0 (https://genemania.org/), further suggested that CDKL2 could act in concert with Casitas B­lineage lymphoma and sphingosine kinase 1 interactor­A­kinase anchoring protein domain­containing genes to regulate the viability of F2­treated Leydig cells. The findings of the present study provide new insights regarding the potential molecular targets associated with the biological effect of E. longifolia extract on cell growth, particularly on the cell cycle, which could aid in enhancing the bioefficacy and reducing the toxicity of this natural product in the future.


Assuntos
Eurycoma/química , Redes Reguladoras de Genes/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Androstenodiona/análogos & derivados , Androstenodiona/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quinases Ciclina-Dependentes/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-cbl/genética , Testosterona/metabolismo
18.
Nutrients ; 12(7)2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32708678

RESUMO

Non-insulin-dependent diabetes mellitus (NIDDM) is a common metabolic disorder worldwide. In addition to the chief feature of long-standing hyperglycemia, dyslipidemia, hyperinsulinemia, and a number of complications develop in parallel. It is believed that an adequate control of blood glucose levels can cause these complications to go into remission. This study was performed to evaluate the antidiabetic activity of Eurycoma longifolia Jack (EL) in vivo. The blood-glucose-lowering activity of EL was studied in db/db mice administered crude powdered EL root (25, 50, and 100 mg/kg) orally for eight weeks. At the end of the study, HbA1c, insulin, plasma lipid levels, and histopathology were performed. Powdered EL root showed significant antihyperglycemic activity along with the control of body weight. After eight weeks of treatment, both the blood cholesterol level and the glycogen deposit in hepatocytes were remarkably lower, whereas the secreting insulin level was elevated. An improvement in islet performance was manifested as an increase in beta-cell number and pancreatic and duodenal homeobox 1 (PDX1) expression. Neogenesis or formation of new islets from pancreatic duct epithelial cells seen in the EL-treated group was encouraging. This study confirms the antihyperglycemic activity of EL through PDX1-associated beta-cell expansion resulting in an enhancement of islet performance.


Assuntos
Eurycoma/química , Proteínas de Homeodomínio/metabolismo , Hiperglicemia/tratamento farmacológico , Células Secretoras de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Transativadores/metabolismo , Administração Oral , Animais , Contagem de Células , Expressão Gênica/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Hiperglicemia/fisiopatologia , Hipoglicemiantes , Células Secretoras de Insulina/fisiologia , Ilhotas Pancreáticas/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Transativadores/genética
19.
J Nat Med ; 74(4): 804-810, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32638295

RESUMO

Two new canthin-6-one alkaloids, 4,9-dimethoxy-5-hydroxycanthin-6-one (1) and 9-methoxy-(R/S)-5-(1-hydroxyethyl)-canthin-6-one (2), together with fifteen known ones were isolated from the roots of Thailand Eurycoma longifolia Jack. Among the known canthin-6-one alkaloids, compounds 9 and 16 were isolated from the Eurycoma genus for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all isolates were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 50 µM. Moreover, a dose-dependent experiment was conducted for active compounds 1, 2, 4, 6, 7, 10, 12-17 at the concentration of 10, 25, and 50 µM, respectively. Consequently, compounds 1, 4, 6, 7, 12, 14, 15, as well as 17 were found to inhibit NO release from RAW264.7 cells in a dose-dependent manner. Two new canthin-6-one alkaloids, 4,9-dimethoxy-5-hydroxycanthin-6-one (1) and 9-methoxy-(R/S)-5-(1-hydroxyethyl)-canthin-6-one (2), together with fifteen known ones were isolated from the roots of Thailand Eurycoma longifolia Jack. Among them, 1, 4, 6, 7, 12, 14, 15, as well as 17 were found to inhibit NO release from RAW264.7 cells in a dose-dependent manner at the concentration of 10, 25, and 50 µM.


Assuntos
Carbolinas/química , Eurycoma/química , Alcaloides Indólicos/química , Extratos Vegetais/química , Raízes de Plantas/química , Tailândia
20.
J Pharm Pharmacol ; 72(9): 1165-1175, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32419149

RESUMO

OBJECTIVES: Eurycoma longifolia Jack (Simaroubaceae) is commonly distributed in the Southeast Asia and Indo China, which has been shown to possess antianxiety, antibacterial, anticancer, antifungal, anti-inflammatory, antimalarial and antioxidant biological activities. 14,15ß-dihydroxyklaineanone is a diterpene isolated from E. longifolia Jack, which is cytotoxic against human lung cancer and human breast cancer cell lines. However, the effects and underlying mechanisms of 14,15ß-dihydroxyklaineanone on hepatocellular carcinoma remain unknown. METHODS: Cell viability assay and colony formation assay were used to measure HepG2 cell proliferation. Flow cytometry was used to analyse cell cycle and apoptosis. Wound-healing assay and transwell assay were used to observe cells migration. RNA sequencing and the enrichment of differentially expressed genes (DEGs) in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to find and determine underlying pathways. KEY FINDINGS: We found that 14,15ß-dihydroxyklaineanone inhibited the growth and migration of HepG2 cells but did not induce cell apoptosis. 14,15ß-dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p-CDK2, cyclin B1, p21, E2F-1 and PCNA. In addition, RNA sequencing showed that 14,15ß-dihydroxyklaineanone regulated MAPK pathway by increasing the expression levels of phosphor-p38. Downregulating of p38 via both p38 inhibitor (SB203580) and p38-siRNA could antagonize the inhibition of cell proliferation and migration and reverse the changes in p-p38, E-cadherin, N-cadherin and PCNA expression induced by 14,15ß-dihydroxyklaineanone treatment. CONCLUSIONS: 14,15ß-dihydroxyklaineanone inhibited cell proliferation and migration through regulating p38 MAPK pathway in HCC cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Eurycoma/química , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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