NF-κB inhibitors from Eurycoma longifolia.
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-κB inhibitors using an NF-κB-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, β-carboline, and canthin-6-one alkaloids are potent NF-κB 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 μM. Eurycomalactone (2), 14,15β-dihydroklaieanone (7), and 13,21-dehydroeurycomanone (10) were identified as potent NF-κB inhibitors with IC50 values of less than 1 μM.
Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck , Austria.
Thi Van Anh
TV
Tran
Clemens
C
Malainer
Stefan
S
Schwaiger
Atanas G
AG
Atanasov
Elke H
EH
Heiss
Verena M
VM
Dirsch
Hermann
H
Stuppner
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002243:Carbolines; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D035701:Eurycoma / Q000737:chemistry*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D026121:Indole Alkaloids; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D036702:Quassins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013185:Squalene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014744:Vietnam
D000470:Alkaloids; D002243:Carbolines; D003374:Coumarins; D005663:Furans; D026121:Indole Alkaloids; D016328:NF-kappa B; D036702:Quassins; C000589161:eurycomalide C; C493363:eurylene; C453379:canthin-6-one; D013185:Squalene