NF-κB Inhibitors from <i>Eurycoma longifolia</i>

The roots of <i>Eurycoma longifolia</i> 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 <i>E. longifolia</i>, 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 (<b>1</b>), together with 27 known compounds including 11 quassinoids (<b>2</b>–<b>12</b>), six alkaloids (<b>13</b>–<b>18</b>), two coumarins (<b>19</b>, <b>20</b>), a squalene derivative (<b>21</b>), a triterpenoid (<b>22</b>), and six phenolic compounds (<b>23</b>–<b>28</b>) from the extract of <i>E. longifolia.</i> 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 (<b>2</b>), 14,15β-dihydroklaieanone (<b>7</b>), and 13,21-dehydroeurycomanone (<b>10</b>) were identified as potent NF-κB inhibitors with IC₅₀ values of less than 1 μM.