Andrographolide protects against cigarette smoke-induced lung inflammation through activation of heme oxygenase-1

J Biochem Mol Toxicol. 2013 May;27(5):259-65. doi: 10.1002/jbt.21483. Epub 2013 Apr 29.

Abstract

This study was conducted to check whether andrographolide, a bioactive molecule isolated from Andrographis paniculata, could protect against cigarette smoke (CS)-induced lung injury through activation of heme oxygenase-1 (HO-1). Pretreatment with andrographolide (1 mg/kg body weight) markedly attenuated lung inflammation in CS-exposed mice, coupled with reduced numbers of total cells, neutrophils, and macrophages in bronchial alveolar lavage fluid (BALF) and decreased production of cytokine/chemokine into BALF. Furthermore, andrographolide pretreatment increased the expression and activation of HO-1 in the lung of CS-exposed animals. Notably, these histological and biochemical changes induced by andrographolide were blocked by prior administration of zinc protoporphyrin IX (ZnPP; 20 mg/kg body weight), a potent heme oxygenase inhibitor. Moreover, andrographolide-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) was attenuated by ZnPP treatment in CS-exposed animals. Our data collectively demonstrate that andrographolide confers protection against CS-induced lung inflammation, partially through activation of HO-1 and STAT3.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokines / metabolism
  • Diterpenes / antagonists & inhibitors
  • Diterpenes / pharmacology*
  • Enzyme Activation / drug effects
  • Heme Oxygenase-1 / metabolism*
  • Lung / enzymology
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Peroxidase / metabolism
  • Pneumonia / chemically induced*
  • Pneumonia / enzymology
  • Pneumonia / prevention & control*
  • Protoporphyrins / pharmacology
  • STAT3 Transcription Factor / drug effects
  • STAT3 Transcription Factor / physiology
  • Signal Transduction / drug effects
  • Smoke / adverse effects*
  • Tobacco Products

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Chemokines
  • Diterpenes
  • Protoporphyrins
  • STAT3 Transcription Factor
  • Smoke
  • zinc protoporphyrin
  • andrographolide
  • Peroxidase
  • Heme Oxygenase-1