Daedalea gibbosasubstances inhibit LPS-induced expression of iNOS by suppression of NF-γB and MAPK activities in RAW 264.7 macrophage cells

Nitric oxide (NO) is a radical molecule produced by iNOS and plays a role in various physiological and pathophysiological conditions including inflammatory diseases and cancer. In the present study, organic extract of Daedalea gibbosa was effective in inhibiting NO and PGE₂ production in RAW 264.7 cells. The extract of D. gibbosa was chemically fractionated leading to the isolation of three active fractions (F5-F7) that were effective in inhibiting NO and iNOS production. In addition, F6 and F7 significantly inhibited the iNOS transcript, while F5 did not cause a reduction in the iNOS transcript. Furthermore, the active fractions showed a differential effect on levels of phospho-p38, phospho-JNK, and phospho-IKBα. Phopsho-p38 was moderately inhibited by F5 and only F7 was significantly active in inhibiting phospho-IKBα. Interestingly, all active fractions significantly enhanced levels of phospho-JNK. In addition, the three active fractions also showed differential inhibitory effects on NF-κB DNA binding activity.