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Daedalea gibbosa substances inhibit LPS-induced expression of iNOS by suppression of NF-κB and MAPK activities in RAW 264.7 macrophage cells

Authors:
Nili Ruimi, Haithem Rwashdeh, Solomon Wasser, Badireenath Konkimalla, Thomas Efferth, Monica Borgatti, Roberto Gambari, Jamal Mahajna

Affiliations:
Cancer Drug Discovery Program, Migal, Galilee Technology Center, Kiryat Shmona, Israel

Doi:
10.3892/ijmm_00000361

Pages:
421-432

Abstract:

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.

International Journal of Molecular Medicine

March 2010
Volume 25 Number 3


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