PI3K/Akt-Nrf2 and Anti-Inflammation Effect of Macrolides in Chronic Obstructive Pulmonary Disease

Curr Drug Metab. 2019;20(4):301-304. doi: 10.2174/1389200220666190227224748.


Background: Chronic Obstructive Pulmonary Disease (COPD) is a systematic inflammatory disease, and smoking is an important risk factor for COPD. Macrolide can reduce COPD inflammation. However, the inflammatory mechanism of COPD remains unclear and the anti-inflammatory mechanism of Macrolide is complex and not exactly known.

Methods: We read and analysed thirty-eight articles, including original articles and reviews.

Results: The expression of Nrf2 was lower in COPD patients and might have a protective role against apoptosis caused by CSE-induced oxidative stress. Nrf2 may play an important role in COPD inflammation. Nrf2 is a key factor in downstream of PI3K/Akt and is involved in the regulation of oxidative stress and inflammatory response. Therefore, PI3K/Akt pathway may play an important role in the activation of Nrf2 and COPD inflammation. Macrolide reduces lung and systemic inflammation of COPD by regulating PI3K/Akt pathway.

Conclusion: This review indicates that PI3K/Ak-Nrf2 may play an important role in COPD inflammation and macrolides may reduce lung and systemic inflammation of COPD by regulating PI3K/Akt-Nrf2 pathway. However, many crucial and essential questions remain to be answered. Further understanding of the mechanisms of macrolide efficacy and PI3K/Akt-Nrf2-mediated inflammatory responses may provide a new clue for exploring COPD treatment in the future.

Keywords: Nrf2 protein; PI3K/Akt pathway; chronic obstructive pulmonary disease; inflammation; macrolides; oxidative stress..

Publication types

  • Review

MeSH terms

  • Gene Expression Regulation / drug effects*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Macrolides / administration & dosage
  • Macrolides / therapeutic use*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism


  • Macrolides
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt