1,8-Cineole Ameliorates LPS-Induced Vascular Endothelium Dysfunction in Mice via PPAR-γ Dependent Regulation of NF-κB

• Main Authors: Ke-Gang Linghu, Guo-Ping Wu, Ling-Yun Fu, Hong Yang, Hai-Zhi Li, Yan Chen, Hua Yu, Ling Tao, Xiang-Chun Shen
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-03-01
• Series: Frontiers in Pharmacology
• Subjects: 1; 8-cineole; human umbilical vein endothelial cell; lipopolysaccharide; NF-κB; PPAR-γ
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2019.00178/full

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.