Inhibition Of Proinflammatory Cytokine Release By Flavones And Flavanones From The Leaves Of Dracaena Steudneri Engl.

The leaves of Dracaena steudneri yielded 6 new flavonoids-3,5,7-trihydroxy-6-methyl-3 ' ,4 ' -methylenedioxyflavone ( 1 ), 5,7-dihydroxy-3-methoxy-6-methyl-3 ' ,4 ' -methylenedioxyflavone ( 2 ), 3,5,7-trihydroxy-6-methoxy-3 ' ,4 ' -methylenedioxyflavone ( 3 ), (2 S ,3 S )-3,7-dihydroxy-6-methoxy-3 ' ,4 ' -methylenedioxyflavanone ( 4 ), 4 ' ,5,7-trihydroxy-3,3 ' ,8-trimethoxy-6-methylflavone ( 5 ), (2 R ) 7-hydroxy-2 ' ,8-dimethoxyflavanone ( 6 )-together with 13 known congeners. Their structures were established using spectroscopic and spectrometric methods including NMR, CD, and HRMS (n) measurements. The compounds were evaluated for their anti-inflammatory potential through measurement of the levels of cytokines IL-1 beta , IL-2, GM-CSF, and TNF- alpha in the supernatant of human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Flavones derivatives 1 - 4 with a C-3 ' /4 ' methylenedioxy substituent led to a substantial increase in the production of IL-1 beta and GM-CSF out of 4 pro-inflammatory cytokines relative to LPS control. Quercetin derivatives 5, 11, and 13 with a hydroxyl group at C-4 ' inhibited the production of IL-2, GM-CSF, and TNF- alpha . The presence of a C-2/C-3 double bond in 14 was pivotal to the significantly stronger (0.4 to 27.5% of LPS control) inhibitory effect compared to its dihydro derivative 8 (36.2 to 262.7% of LPS control) against all tested cytokines. It is important to note that the inhibitory activity of 14 was substantially higher than that of the standard drug used, ibuprofen.