β-Caryophyllene attenuates lipopolysaccharide-induced acute lung injury via inhibition of the MAPK signalling pathway

J Pharm Pharmacol. 2021 Sep 7;73(10):1319-1329. doi: 10.1093/jpp/rgab074.

Abstract

Objectives: Acute lung injury (ALI) is a pulmonary manifestation of an acute systemic inflammatory response, which is associated with high morbidity and mortality. Accordingly, from the perspective of treating ALI, it is important to identify effective agents and elucidate the underlying modulatory mechanisms. β-Caryophyllene (BCP) is a naturally occurring bicyclic sesquiterpene that has anti-cancer and anti-inflammatory activities. However, the effects of BCP on ALI have yet to be ascertained.

Methods: ALI was induced intratracheally, injected with 5 mg/kg LPS and treated with BCP. The bone marrow-derived macrophages (BMDMs) were obtained and cultured then challenged with 100 ng/ml LPS for 4 h, with or without BCP pre-treatment for 30 min.

Key findings: BCP significantly ameliorates LPS-induced mouse ALI, which is related to an alleviation of neutrophil infiltration and reduction in cytokine production. In vitro, BCP was found to reduce the expression of interleukin-6, interleukin-1β and tumour necrosis factor-α, and suppresses the MAPK signalling pathway in BMDMs, which is associated with the inhibition of TAK1 phosphorylation and an enhancement of MKP-1 expression.

Conclusions: Our data indicate that BCP protects against inflammatory responses and is a potential therapeutic agent for the treatment of LPS-induced acute lung injury.

Keywords: acute lung injury; inflammation; lipopolysaccharide; mitogen-activated protein kinase phosphatase 1; transforming growth factor β-activated kinase 1; β-caryophyllene.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / prevention & control
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cells, Cultured
  • Cytokines / metabolism
  • Dual Specificity Phosphatase 1 / metabolism
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Inflammation / prevention & control
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides
  • Lung / drug effects*
  • Lung / metabolism
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Polycyclic Sesquiterpenes / pharmacology*
  • Polycyclic Sesquiterpenes / therapeutic use
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes / therapeutic use
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Plant Extracts
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • caryophyllene
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, mouse