Here, we demonstrate for the first time a 1,8-cineol-depending reduction of NF-魏B-activity in human cell lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS). Immunocytochemistry further revealed a reduced nuclear translocation of NF-魏B p65, while qPCR and western blot analyses showed strongly attenuated expression of NF-魏B target genes. Treatment with 1,8-cineol further led to increased protein levels of I魏B伪 in an IKK-independent matter, while FRET-analyses showed restoring of LPS-associated loss of interaction between NF-魏B p65 and I魏B伪. 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-魏B p65 and reduction of its target gene I魏B伪 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-魏B p65 translocation via I魏B伪 resulting in decreased levels of proinflammatory NF-魏B target genes and may therefore broaden the field of clinical application of this natural drug for treating inflammatory diseases.