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Cloricromene, a Semi-Synthetic Coumarin Derivative, Inhibits Tumor Necrosis Factor-Alpha Production at a Pre-Transcriptional Level

Cloricromene, a Semi-Synthetic Coumarin Derivative, Inhibits Tumor Necrosis Factor-Alpha Production at a Pre-Transcriptional Level

E Corsini, L Lucchi, M Binaglia, B Viviani, C Bevilacqua, G Monastra, M Marinovich, C L Galli

Eur J Pharmacol. 2001 Apr 27;418(3):231-7.

PMID: 11343695

Abstract:

Cloricromene decreases myocardial infarct size after ischemic-reperfusion injury in vivo, and it has been suggested that this is due to inhibition of tumor necrosis factor-alpha (TNF-alpha). The purpose of this work was to characterize the mechanism of cloricromene-induced inhibition of TNF-alpha in rat macrophages. Cloricromene inhibited lipopolysaccharide-induced TNF-alpha release in a dose-dependent manner (IC(50)=5.9 +/- 0.8 microM). This was not due to cytotoxicity, as cloricromene was well tolerated up to 500 microM. Cloricromene inhibited lipopolysaccharide-induced expression of TNF-alpha mRNA, which suggests a pre-transcriptional effect. We then investigated the early signal transduction pathway triggered by lipopolysaccharide. The binding of lipopolysaccharide to its receptor CD14 activates protein kinase C and nuclear factor-kappaB (NF-kappaB). Cloricromene inhibited NF-kappaB activation in a dose-dependent manner, but affected protein kinase C translocation only slightly. We then established that cloricromene inhibited lipopolysaccharide-induced cellular oxidative activity, which is important for NF-kappaB activation. Our results show that cloricromene interferes with the early signal transduction pathway triggered by lipopolysaccharide.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP74697282	Cloricromene		74697-28-2	Price

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