Cancer Drug Discovery Program, Migal, Galilee Technology Center, Kiryat Shmona, Israel.
Int J Mol Med. 2010 Mar;25(3):421-32. doi: 10.3892/ijmm_00000361.
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-IKBalpha. Phopsho-p38 was moderately inhibited by F5 and only F7 was significantly active in inhibiting phospho-IKBalpha. Interestingly, all active fractions significantly enhanced levels of phospho-JNK. In addition, the three active fractions also showed differential inhibitory effects on NF-kappaB DNA binding activity.
一氧化氮(NO)是一种由 iNOS 产生的自由基分子,在包括炎症性疾病和癌症在内的各种生理和病理生理条件下发挥作用。在本研究中,长根菇有机提取物能有效抑制 RAW 264.7 细胞中 NO 和 PGE2 的产生。D. gibbosa 的提取物经化学分离得到三个具有活性的馏分(F5-F7),能有效抑制 NO 和 iNOS 的产生。此外,F6 和 F7 显著抑制 iNOS 转录,而 F5 并未导致 iNOS 转录减少。此外,活性馏分对磷酸化 p38、磷酸化 JNK 和磷酸化 IKBalpha 的水平表现出不同的影响。F5 适度抑制磷酸化 p38,只有 F7 能显著抑制磷酸化 IKBalpha。有趣的是,所有活性馏分均显著增加磷酸化 JNK 的水平。此外,这三个活性馏分对 NF-κB DNA 结合活性也表现出不同的抑制作用。