eurycomanone and eurycomanol

Quassinoids, the major secondary metabolites of

Topics: Eurycoma; Magnetic Resonance Spectroscopy; Metabolomics; Molecular Structure; Plant Extracts; Plant Roots; Quassins

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.

Topics: Cell Death; Cell Proliferation; Eurycoma; Humans; Inflammation; Jurkat Cells; Leukemia; Leukocytes, Mononuclear; NF-kappa B; Plant Extracts; Quassins; Signal Transduction

Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5μg/ml. TAF273 (50μg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.

Topics: Angiogenesis Inhibitors; Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Chick Embryo; Chorioallantoic Membrane; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Endothelial Cells; Eurycoma; Human Umbilical Vein Endothelial Cells; Humans; K562 Cells; Leukemia, Erythroblastic, Acute; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Neovascularization, Physiologic; Phytotherapy; Plant Extracts; Plant Roots; Plants, Medicinal; Quassins; Rats; Rats, Sprague-Dawley; Time Factors; Xenograft Model Antitumor Assays