Planta Med 2005; 71(6): 514-519
DOI: 10.1055/s-2005-864151
Original Paper
Biochemistry and Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

Laxifolone A Suppresses LPS/IFN-γ-Induced NO Synthesis by Attenuating NF-κB Translocation: Role of NF-κB p105 Level

Han-Chieh Ko1 , Yao-Haur Kuo1 , Bai-Luh Wei2 , Wen-Fei Chiou1 , 2
  • 1Division of Basic Chinese Medical Research, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC
  • 2Institute of Life Science, National Taitung University, Taitung, Taiwan, ROC
Weitere Informationen

Publikationsverlauf

Received: August 23, 2004

Accepted: January 5, 2005

Publikationsdatum:
21. Juni 2005 (online)

Abstract

Laxifolone A is a triterpene isolated from Euonymus laxiflorus Champ. Exposure of RAW264.7 macrophages to laxifolone A concentration-dependently suppressed lipopolysaccharide/interferon-γ (LPS/IFN-γ)-induced nitrite production (IC50 = 0.37 ± 0.05 μM), inducible NO synthase (iNOS) protein, and iNOS mRNA expression. Translocation of nuclear factor-κB (NF-κB) into the nucleus with subsequent activation of iNOS gene transcription is essential in NO signaling. Western blot analysis indicated that the cytosolic NF-κB/p65 was obviously decreased after LPS/IFN-γ stimulation for 30 min and this phenomenon could be reversed by laxifolone A. Similarly, a time-related NF-κB/p65 nuclear translocation induced by LPS/IFN-γ was diminished in the presence of laxifolone A. However, laxifolone A failed to interfere in LPS/IFN-γ-evoked IκB degradation. Our results also showed that LPS/IFN-γ-stimulation resulted in the degradation of NF-κB p105, the NF-κB precursor, and laxifolone A treatment significantly counteracted this effect. Furthermore, laxifolone A itself was able to enhance NF-κB p105 protein expression. In summary, these results suggest that inhibition of NF-κB p105 degradation in cytoplasm may participate in the abrogation of LPS/IFN-γ-induced NF-κB translocation and subsequent NO synthesis by laxifolone A.

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Wen-Fei Chiou, Ph. D.

Division of Basic Chinese Medical Research

National Research Institute of Chinese Medicine

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