Anti-Inflammatory Activity of Geraniol Isolated from Lemon Grass on Ox-LDL-Stimulated Endothelial Cells by Upregulation of Heme Oxygenase-1 via PI3K/Akt and Nrf-2 Signaling Pathways

Nutrients. 2022 Nov 14;14(22):4817. doi: 10.3390/nu14224817.

Abstract

Among the world's leading causes of cardiovascular disease, atherosclerosis is a chronic inflammatory disorder that affects the arteries. Both vasodilation and vasoconstriction, low levels of nitric oxide and high levels of reactive oxygen species and pro-inflammatory factors characterize dysfunctional blood vessels. Hypertension, and atherosclerosis, all start with this dysfunction. Geraniol, a compound of acyclic monoterpene alcohol, found in plants such as geranium, lemongrass and rose, is a primary constituent of essential oils. It shows a variety of pharmacological properties. This study aimed to investigate the impact of geraniol on Ox-LDL-induced stress and inflammation in human umbilical vein endothelial cells. In this study, HUVECs were treated with Ox-LDL or geraniol at different dose concentrations. MTT assay, Western blot, ROS generation and DNA fragmentation were used to evaluate geraniol's effects on Ox-LDL-induced HUVECs inflammation. The results show that geraniol pre-incubation ameliorates Ox-LDL-mediated HUVECs cytotoxicity and DNA fragmentation. The geraniol inhibited the production of pro-inflammatory cytokines by Ox-LDL, including TNF-α, IL-6 and IL-1β. In Ox-LDL-stimulated HUVECs, geraniol suppresses the nuclear translocation and activity of NF-ᴋB as well as phosphorylation of IkBα. Moreover, geraniol activated the PI3K/AKT/NRF2 pathway in HUVECs, resulting in an increase in the expression of HO-1. Taking our data together, we can conclude that, in HUVECs, geraniol inhibits Ox-LDL-induced inflammation and oxidative stress by targeting PI3/AKT/NRF2.

Keywords: Ox-LDL; anti inflammation; geraniol; oxidative stress.

MeSH terms

  • Acyclic Monoterpenes
  • Anti-Inflammatory Agents / therapeutic use
  • Atherosclerosis* / metabolism
  • Cymbopogon* / metabolism
  • Heme Oxygenase-1 / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Up-Regulation

Substances

  • oxidized low density lipoprotein
  • Heme Oxygenase-1
  • geraniol
  • Acyclic Monoterpenes
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • NF-E2-Related Factor 2
  • Anti-Inflammatory Agents