Tomatidine inhibits iNOS and COX-2 through suppression of NF-κB and JNK pathways in LPS-stimulated mouse macrophages

Chiu, Feng-Lan; Lin, Jen-Kun

doi:10.1016/j.febslet.2008.05.049

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Volume 582, Issue 16 , Pages 2407-2412, 9 July 2008

Tomatidine inhibits iNOS and COX-2 through suppression of NF-κB and JNK pathways in LPS-stimulated mouse macrophages

Edited by Beat Imhof

Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1 Section 1, Jen-ai Road, Taipei 10018, Taiwan

Received 30 March 2008; received in revised form 30 May 2008; accepted 30 May 2008. published online 09 June 2008.

Abstract

We use the LPS-stimulated macrophage as a model of inflammation to investigate the anti-inflammatory effects of tomatidine and solasodine, whose structures resemble glucocorticoids. We found that tomatidine exhibited a more potent anti-inflammatory effect than solasodine. Tomatidine could decrease inducible nitric oxide synthase and cyclooxygenase-2 expression through suppression of I-κBα phosphorylation, NF-κB nuclear translocation and JNK activation, which in turn inhibits c-jun phosphorylation and Oct-2 expression. Here, we demonstrate that tomatidine acts as an anti-inflammatory agent by blocking NF-κB and JNK signaling, and may possibly be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.

Keywords: Tomatidine, iNOS, COX-2, NF-κB, JNK, AP-1, Oct-2