Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities.
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ABSTRACT:
SUBMITTER: Yang WQ
PROVIDER: S-EPMC8512324 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Four new phenolic components, eurylophenolosides A (1) and B (2), eurylolignanosides A (3) and B (4), along with twelve known compounds were isolated from the roots of Eurycoma longifolia Jack. The structure of these components was elucidated by using various spectral techniques and chemical reactions. Among the known isolates, syringaldehyde (12), 3-chloro-4-hydroxybenzoic acid (13), 3-chloro-4-hydroxyl benzoic acid-4-O-β-d-glucopyranoside (14), and isotachioside (15) were isolated from the Eurycoma genus for the first time. Further, the NMR data of 14 was reported here firstly. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 40 μM. As results, piscidinol A (6), 24-epi-piscidinol A (7), bourjotinolone A (10), and scopoletin (16) were found to play important role in suppressing NO levels without cytotoxicity. Furthermore, the Western blot method was used to investigate the mechanism of compounds 6, 7, 10, and 16 by analysing the level of inflammation related proteins, such as inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated RAW264.7 cells. Consequently, compounds 6, 7, 10, and 16 were found to significantly inhibit LPS-induced protein expression of IL-6, NF-κB and iNOS in NF-κB signaling pathway. Moreover, it was found that the protein expression inhibitory effects of 6, 7, and 16 exhibited in a dose-dependent manner. The mechanism may be related to the inhibition of the iNOS expressions through suppressing the IL-6-induced NF-κB pathway.
| S-EPMC6749187 | biostudies-other
Project description:Eurycoma longifolia Transcriptome or Gene expression
| PRJNA297259 | ENA
Project description:The roots of Eurycoma longifolia have been used in many countries of Southeast Asia to alleviate various diseases including malaria, dysentery, sexual insufficiency, and rheumatism. Although numerous studies have reported the pharmacological properties of E. longifolia, the mode of action of the anti-inflammatory activity has not been elucidated. Bioguided isolation of NF-?B inhibitors using an NF-?B-driven luciferase reporter gene assay led to the identification of a new quassinoid, eurycomalide C (1), together with 27 known compounds including 11 quassinoids (2-12), six alkaloids (13-18), two coumarins (19, 20), a squalene derivative (21), a triterpenoid (22), and six phenolic compounds (23-28) from the extract of E. longifolia. Evaluation of the biological activity revealed that C19-type and C20-type quassinoids, ?-carboline, and canthin-6-one alkaloids are potent NF-?B inhibitors, with IC50 values in the low micromolar range, while C18-type quassinoids, phenolic compounds, coumarins, the squalene derivative, and the triterpenoid turned out to be inactive when tested at a concentration of 30 ?M. Eurycomalactone (2), 14,15?-dihydroklaieanone (7), and 13,21-dehydroeurycomanone (10) were identified as potent NF-?B inhibitors with IC50 values of less than 1 ?M.
| S-EPMC3971761 | biostudies-literature
Project description: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.
| S-EPMC8838174 | biostudies-literature
Project description:Eurycomanone (EN) is one of the representative quassinoid diterpenoids from roots of Eurycoma longifolia Jack, a natural medicine that is widely distributed in Southeast Asia. Previous studies showed that EN induces cancer cell apoptosis and exhibits anti-cancer activity, but the molecular mechanism of EN against cancer has still not been elucidated. In this study, we examined the regulatory effect of EN on autophagy to reveal the mechanism of EN-mediated colon cancer growth inhibition. First, we found that EN is able to inhibit colon cancer cell proliferation and colony formation. The angiogenesis level in cancer cells was inhibited as well. Next, the treatment of EN led to the suppression of autophagy, which was characterized by the downregulation of the LC3-II level and the formation of GFP-LC3 puncta under EN treatment in colon cancer. Moreover, we revealed that the mTOR signaling pathway was activated by EN in a time- and concentration-dependent manner. Finally, autophagy induction protected colon cancer cells from EN treatment, suggesting that autophagy improves cell survival. Taken together, our findings revealed the mechanism of EN against colon cancer through inhibiting autophagy and angiogenesis in colon cancer, supporting that the autophagy inhibitor EN could be developed to be a novel anti-cancer agent.
| S-EPMC9324291 | biostudies-literature
Project description:This study investigated the effect of treatment with the proprietary standardized, water-soluble extract of the root of the Malaysian plant, Eurycoma longifolia Jack, which is thought to enhance male fertility with regard to higher semen volumes, sperm concentrations, the percentage of normal sperm morphology and sperm motility in male partners of sub-fertile couples with idiopathic infertility. A total of 350 patients were given 200 mg of the extract daily and follow-up semen analyses were performed every 3 months for 9 months. Of these 350 patients, 75 patients completed one full cycle of 3 months. Follow-up semen analyses in these patients showed significant improvement in all semen parameters. The proprietary extract of Eurycoma longifolia Jack significantly improved the sperm quality in these patients, allowing for 11 (14.7%) spontaneous pregnancies.
| S-EPMC3739276 | biostudies-other
Project description:Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells. Interestingly, eurycomanone inhibited NF-κB signaling through inhibition of IκBα phosphorylation and upstream mitogen activated protein kinase (MAPK) signaling, but not eurycomanol. In conclusion, both quassinoids present differential toxicity towards leukemia cells, and the presence of the α,β-unsaturated ketone in eurycomanone could be prerequisite for the NF-κB inhibition.
| S-EPMC6270735 | biostudies-literature
Project description:Eurycoma longifolia is a popular folk medicine in South East Asia. This study was focused on saccharide-containing compounds including saponins, mainly because of their medical potentials. Different organic solvents such as ethyl acetate, butanol, and chloroform were used to fractionate the phytochemical groups, which were consequently precipitated in cold acetone. Solvent fractionation was found to increase the total saponin content based on colorimetric assay using vanillin and sulfuric acid. Ethyl acetate fraction and its precipitate were showed to have the highest crude saponins after acetone precipitation. The samples were shown to have anti-proliferative activity comparable with tamoxifen (IC50 = 110.6 µg/mL) against human breast cancer cells. The anti-proliferative activities of the samples were significantly improved from crude extract (IC50 = 616.3 µg/mL) to ethyl acetate fraction (IC50 = 185.4 µg/mL) and its precipitate (IC50 = 153.4 µg/mL). LC-DAD-MS/MS analysis revealed that the saccharide-containing compounds such as m/z 497, 610, 723, 836, and 949 were abundant in the samples, and they could be ionized in negative ion mode. The compounds consisted of 226 amu monomers with UV-absorbing property at 254 nm, and were tentatively identified as formylated hexoses. To conclude, solvent fractionation and acetone precipitation could produce saccharide-containing compounds including saponins with higher anti-proliferative activity than crude extract against MCF-7 cells. This is the first study to use non-toxic solvents for fractionation of bioactive compounds from highly complex plant extract of E. longifolia.
| S-EPMC6480193 | biostudies-literature
Project description:Background: Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia. The stems are traditionally used for the treatment of sexual insufficiency, fever, hypertension, and malaria. Furthermore, it has antidiabetic and anticancer activities. Recently, it has been reported to reduce uric acid, but the mechanism is unclear. Hypothesis/Purpose: The aim of this study is to explore the effect and mechanism of E. longifolia stem 70% ethanol extract (EL) and its active compounds on uric acid excretion. Study Design and Methods: Potassium oxonate (PO) induced hyperuricemia rats model and adenine-PO induced hyperuricemia mice model were used to evaluate the effects of EL. Ultraperformance liquid chromatography was used to determine the levels of plasma or serum uric acid and creatinine. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and western blot was applied to detect protein expression levels of uric acid transporters. Effects of constituents on urate uptake were tested in hURAT1-expressing HEK293T cells. Results: EL significantly reduced serum and plasma uric acid levels at dosages of 100, 200, and 400 mg/kg in hyperuricemia rats and mice, increased the clearance rate of uric acid and creatinine, and improved the renal pathological injury. The protein expression levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 were down-regulated, while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treatment. The quassinoids isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells, and the effect of eurycomanol was further confirmed in vivo. Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.
| S-EPMC6914847 | biostudies-literature