Evaluation of quassinoids from Eurycoma longifolia roots for anti-inflammatory activity.

Phytochemical investigation of the roots of Eurycoma longifolia led to the discovery of eighteen structurally diverse quassinoids (1‒18), including fourteen previously undescribed ones (1, 3‒5, and 7‒16). Among the isolated compounds, compounds 1‒6 are three pairs of unusual C-20 epimeric C25 quassinoids. Compounds 7‒15 are nine C19 quassinoids belonging to three distinct carbon skeleton types. Compounds 16‒18 are three C18 quassinoids; notably, compound 16 features an unprecedented lactone bridge between C-9 and C-14. The chemical structures of the compounds, including absolute configurations, were elucidated by comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum-chemical electronic circular dichroism calculations. Biological evaluations revealed that compounds 7 and 18 significantly inhibited nitric oxide production, interleukin-1β secretion, and inducible nitric oxide synthase expression in lipopolysaccharide-stimulated RAW264.7 cells, suggesting their potential anti-inflammatory activity.