Nerolidol Suppresses the Inflammatory Response during Lipopolysaccharide-Induced Acute Lung Injury via the Modulation of Antioxidant Enzymes and the AMPK/Nrf-2/HO-1 Pathway

Oxid Med Cell Longev. 2019 Nov 16:2019:9605980. doi: 10.1155/2019/9605980. eCollection 2019.


Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / metabolism*
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects*


  • Anti-Inflammatory Agents
  • Antioxidants
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Sesquiterpenes
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • AMP-Activated Protein Kinases
  • nerolidol