title: Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function.
abstract: 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.
authors.affiliation: Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia (USM), 13200 Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Omar Saeed Ali
authors.initials: OS
authors.lastname: Al-Salahi
authors.forename: Chan
authors.initials: C
authors.lastname: Kit-Lam
authors.forename: Amin Malik Shah Abdul
authors.initials: AM
authors.lastname: Majid
authors.forename: Fouad Saleih R
authors.initials: FS
authors.lastname: Al-Suede
authors.forename: Sultan Ayesh
authors.initials: SA
authors.lastname: Mohammed Saghir
authors.forename: Wan Zaidah
authors.initials: WZ
authors.lastname: Abdullah
authors.forename: Mohamed B Khadeer
authors.initials: MB
authors.lastname: Ahamed
authors.forename: Narazah Mohd
authors.initials: NM
authors.lastname: Yusoff
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D035701:Eurycoma; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D036702:Quassins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D010936:Plant Extracts; D036702:Quassins; C506425:eurycomanone; C093532:eurycomanol