Malloapelta B suppresses LPS-induced NF-κB activation and NF-κB-regulated target gene products.

Abstract

Nuclear factor-κB (NF-κB) and the signaling pathways that regulate its activity have become a focal point for intense drug research and development efforts. NF-κB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and anti-apoptotic responses. In our search for NF-κB inhibitors from natural resources, we identified malloapelta B as an inhibitor of NF-κB activation from Mallotus apelta Muell-Arg. In the present study, we demonstrated the effect of malloapelta B on NF-κB activation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This compound suppressed NF-κB activation through the inhibition of IκB kinase (IKK) activation, thereby blocking the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and the nuclear translocation and DNA-binding activity of p65. The suppression of NF-κB by malloapelta B led to the down-regulation of target genes involved in inflammation and proliferation. Taken together, this study extends our understanding on the mechanisms underlying the possible anti-inflammatory and anti-cancer activities of malloapelta B. Our findings provide new insight into its mechanisms of action and propose a potential application of malloapelta B for inflammatory diseases as well as certain cancers associated with abnormal NF-κB activation.

• Authors: Juan Ma, Hui Shi, Chunliu Mi, Hong Lan Li, Jung Joon Lee, Xuejun Jin
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 24 Issue 2 Pg. 147-152 (Feb 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25510584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Benzopyrans
• Lipopolysaccharides
• NF-kappa B
• Rela protein, mouse
• Transcription Factor RelA
• malloapelta B

Topics

• Animals
• Benzopyrans (isolation & purification, pharmacology)
• Cell Line
• Cell Nucleus (metabolism)
• Cell Proliferation (genetics)
• Inflammation (genetics)
• Lipopolysaccharides (immunology)
• Macrophages (drug effects, immunology)
• Mallotus Plant (immunology)
• Mice
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Protein Transport
• Transcription Factor RelA (metabolism)
• Transcriptional Activation (drug effects)