Inducible nitric oxide synthase inhibitors of Chinese herbs. Part 2: Naturally occurring furanocoumarins

Ching-Chiung Wang, Jing-Erh Lai, Lih Geeng Chen, Kun Ying Yen, Ling-Ling Yang

研究成果: 雜誌貢獻文章同行評審

53 引文 斯高帕斯(Scopus)

摘要

Inducible nitric oxide synthase (iNOS)-dependent production of nitric oxide (NO) plays an important role in inflammation. The effects of various naturally occurring furanocoumarins on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells were evaluated in vitro. The results showed that angelicin, pimpinellin, sphondin, byakangelicol, oxypeucedanin, oxypeucedanin hydrate, xanthotoxin, and cnidilin are potential NO production inhibitors, and their IC50 values for inhibition of nitrite production were 19.5, 15.6, 9.8, 16.9, 16.8, 15.8, 16.6, and 17.7μg/mL, respectively. Distinct structure-activity relationships were also revealed for the NO production inhibitory activities of these furanocoumarins. Activities of the angelicin type such as pimpinellin and sphondin were more potent than those of the psoralen type. Presence of a methoxy at the C6 position in the angelicin type seemed to be essential to augment the activity. Western blot analysis demonstrated that only sphondin dose-dependently inhibited the expression of the iNOS protein at 2.5-20μg/mL. However, iNOS enzyme activity was stimulated with LPS for 12h and sphondin was administered (20μg/mL) for 24h, which did not reasonably inhibit iNOS enzyme activity. L-NAME (100μM), a known specific inhibitor of iNOS, was employed as a positive control with the same protocol and showed more than 50% inhibition activity. The results demonstrate that the NO production inhibitory activity of sphondin is due to the effect of iNOS expression, but not by direct inhibition of iNOS enzyme activity. Thus, sphondin may act as a potent inhibitor of NO production under tissue-damaging inflammatory conditions. Copyright (C) 2000 Elsevier Science Ltd.
原文英語
頁(從 - 到)2701-2707
頁數7
期刊Bioorganic and Medicinal Chemistry
8
發行號12
DOIs
出版狀態已發佈 - 2000

ASJC Scopus subject areas

  • 生物化學
  • 分子醫學
  • 分子生物學
  • 藥學科學
  • 藥物發現
  • 臨床生物化學
  • 有機化學

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