NF-κB Inhibitors from Eurycoma longifolia

Abstract

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.

The Quassinoid Isobrucein B Reduces Inflammatory Hyperalgesia and Cytokine Production by Post-transcriptional Modulation

“…These apparent contradictory effects of 1 compared to other quassinoids, such as brucein D 25 and quassinoids isolated from Eurycoma longifolia, 26 are very probably dependent upon Mice were pretreated sc with vehicle or 1 (0.5, 1, and 5 mg/ kg) 1 h before intraplantar injection of carrageenan. Three hours after carrageenan injection plantar tissues were collected for quantification of neutrophil migration by MPO activity.…”

“…[27][28][29][30]32 For quassinoids from Eurycoma longifolia, the conclusions were based only on an NF-κB reporter assay after TNF stimulation. 26 Since 1 might not act by blocking transcriptional activity of NF-κB but could instead be inhibiting the production/release of NF-κB-dependent cytokines, the next hypothesis was that 1 activities could likely be mediated by modulation of posttranscriptional mechanisms. To confirm this hypothesis, we used RAW 264.7 cells transfected with the luciferase gene vector controlled by a phosphoglycerate kinase promoter (PKG), a nonviral universal promoter, a region that promotes the recruitment of transcription factors nonspecifically.…”

A New Canthinone-Type Alkaloid Isolated from Ailanthus altissima Swingle

“…However a further study is needed to ensure a structure-activity relationship for the canthin-6-one alkaloids. In a previously study, 9-hydroxycanthin-6-one (4) was reported to inhibit the NF-κB pathway in TNF-a-stimulated HEK-293/NF-kB-luc cells [31]. Among the isolates, sinapaldehyde (9) was found to have the most potent inhibitory effect with an observed IC50 value of 5.92 μM, and erythro-guaiacylglycerol-β-O-4′-coniferyl ether (11) also showed a significant inhibitory effect with an Although 4-hydroxycanthin-6-one (3), 9-hydroxycanthin-6-one (4), 10-hydroxycanthin-6-one (5), and 11-hydroxycanthin-6-one (6) were isolated from the Simaroubaceae family, they have not been reported from A. altissima.…”

A new anti-inflammatory β-carboline alkaloid from the hairy-root cultures of Eurycoma longifolia

“…NGOC ET AL. (Kuo et al 2003;Park et al 2014;Tran et al 2014). However, E. longifolia roots are harvested after several years of cultivation, i.e.…”