Abstract
1,8-Cineole (eucalyptol), a monoterpene, has been widely reported for the anti-inflammatory effects. Our previous data confirmed that 1,8-cineole ameliorated the inflammatory phenotype of human umbilical vein endothelial cells (HUVECs) by mediating NF-κB expression in vitro. At present, we investigated the protection effects of 1,8-cineole on vascular endothelium in lipopolysaccharide (LPS)-induced acute inflammatory injury mice and the potential mechanisms involved in the protection in HUVECs. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed the secretion of interleukin (IL)-6 and IL-8 and increased the expression of IL-10 in the serum of LPS-induced mice. 1,8-Cineole reduced the inflammatory infiltration and the expression of vascular cell adhesion molecular 1 (VCAM-1) in the sections of thoracic aorta in LPS-induced acute inflammatory mice. Western blotting indicated that 1,8-cineole significantly decreased the phosphorylation of NF-κB p65 and increased the expression of PPAR-γ in the thoracic aorta tissue. 1,8-Cineole increased the expression of PPAR-γ in LPS-induced HUVECs. 1,8-Cineole and rosiglitazone reduced the protein and mRNA levels of VCAM-1, E-selectin, IL-6, and IL-8 in LPS-induced HUVECs, which could be reversed by the action of GW9662 (inhibitor of PPAR-γ). 1,8-Cineole and rosiglitazone blocked the LPS-induced IκBα degradation and NF-κB p65 nucleus translocation, which could be reversed by the pretreatment of GW9662 or silence of PPAR-γ gene. In conclusion, 1,8-cineole attenuated LPS-induced vascular endothelial cells injury via PPAR-γ dependent modulation of NF-κB.
Highlights
Cardiovascular diseases (CVDs), emerging from the dysfunction of vascular endothelium, are the leading cause of death worldwide (Mollenhauer et al, 2018)
1,8-Cineole with a purity >99.5% by gas chromatography analysis was obtained from Aladdin (Shanghai, China). 1,8-Cineole was dissolved in Tween 20 as a stock solution, and diluted with normal saline before intragastric administration to mice. 1,8-Cineole was dissolved in dimethyl sulfoxide (DMSO) as a stock solution, and diluted with endothelial cell medium (ECM) before each cell experiment
We investigated the protective effects of 1,8-cineole on vascular endothelium in LPS-induced acute inflammatory injury mice, and the potential molecule mechanisms involved in the protection in human umbilical vein endothelial cells (HUVECs)
Summary
Cardiovascular diseases (CVDs), emerging from the dysfunction of vascular endothelium, are the leading cause of death worldwide (Mollenhauer et al, 2018). It is well known that inflammation in the pathophysiological process of injured endothelium would deteriorate the damage of endothelial cells and go through the whole process of CVDs (Castellon and Bogdanova, 2016). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates expression of many pro-inflammatory proteins, cytokines, chemokines, and adhesion molecules (Sokolova and Naumann, 2017). Ligand-activated PPAR-γ decreased the inflammatory responses in cardiovascular cells, in endothelial cells (Lim et al, 2015). It is known that PPAR-γ activation leads to the repression of pro-inflammatory genes such as cyclooxygenase 2, inducible nitric oxide synthase and interleukin (IL)-6, and the reduction of cytokines and acute phase proteins by inhibiting the NF-κB pathway (Yang et al, 2014). Inhibition of NF-κB by PPAR-γ agonists were reported to reduce the generation of pro-inflammatory mediators/responses (Mingfeng et al, 2014; Marcone et al, 2015; Su et al, 2017)
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