1,8-Cineol inhibits nuclear translocation of NF-κB p65 and NF-κB-dependent transcriptional activity

https://doi.org/10.1016/j.bbamcr.2013.07.001Get rights and content
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Highlights

  • A novel mode of action of 1,8-cineol via inhibition of NF-κB

  • 1,8-Cineol-depending decrease of NF-κB-activity in human cell lines U373 and HeLa

  • 1,8-Cineol treatment led to reduced amount of nuclear p65 in U373, HeLa and hPBMCs.

  • Reduced levels of NF-κB target genes and increased amount of IκBα by 1,8-cineol

  • Restoring of LPS-dependent loss of interaction between p65 and IκBα by 1,8-cineol

Abstract

Natural plant-derived products are commonly applied to treat a broad range of human diseases, including cancer as well as chronic and acute airway inflammation. In this regard, the monoterpene oxide 1,8-cineol, the active ingredient of the clinically approved drug Soledum®, is well-established for the therapy of airway diseases, such as chronic sinusitis and bronchitis, chronic obstructive pulmonary disease and bronchial asthma. Although clinical trials underline the beneficial effects of 1,8-cineol in treating inflammatory diseases, the molecular mode of action still remains unclear.

Here, we demonstrate for the first time a 1,8-cineol-depending reduction of NF-κB-activity in human cell lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS). Immunocytochemistry further revealed a reduced nuclear translocation of NF-κB p65, while qPCR and western blot analyses showed strongly attenuated expression of NF-κB target genes. Treatment with 1,8-cineol further led to increased protein levels of IκBα in an IKK-independent matter, while FRET-analyses showed restoring of LPS-associated loss of interaction between NF-κB p65 and IκBα. We likewise observed reduced amounts of phosphorylated c-Jun N-terminal kinase 1/2 protein in U373 cells after exposure to 1,8-cineol. In addition, 1,8-cineol led to decreased amount of nuclear NF-κB p65 and reduction of its target gene IκBα at protein level in human peripheral blood mononuclear cells.

Our findings suggest a novel mode of action of 1,8-cineol through inhibition of nuclear NF-κB p65 translocation via IκBα resulting in decreased levels of proinflammatory NF-κB target genes and may therefore broaden the field of clinical application of this natural drug for treating inflammatory diseases.

Keywords

1,8-Cineol
NF-κB
Human cell lines
PBMCs
Inflammation
Inflammatory diseases

Cited by (0)

1

Present address: Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA.

2

The authors have equal contributions.