Brevenal, a Marine Natural Product, is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells

Mar Drugs. 2019 Mar 20;17(3):184. doi: 10.3390/md17030184.


Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma, are some of the leading causes of illness and fatalities worldwide. The search for novel treatments led to the exploration of marine natural products as drug candidates to combat the debilitating effects of mucus accumulation and chronic inflammation. Previous research showed that an alga-derived compound, brevenal, could attenuate the effects of inflammatory agents, but the mechanisms by which it exerted its effects remained unclear. We investigated the effects of brevenal on lipopolysaccharide (LPS) induced cytokine/chemokine production from murine macrophages and human lung epithelial cells. It was found that brevenal reduces proinflammatory mediator secretion while preserving anti-inflammatory secretion from these cells. Furthermore, we found that brevenal does not alter cell surface Toll-like receptor 4 (TLR4) expression, thereby maintaining the cells' ability to respond to bacterial infection. However, brevenal does alter macrophage activation states, as demonstrated by reduced expression of both M1 and M2 phenotype markers, indicating this putative anti-inflammatory drug shifts innate immune cells to a less active state. Such a mechanism of action would be ideal for reducing inflammation in the lung, especially with patients suffering from chronic respiratory diseases, where inflammation can be lethal.

Keywords: COPD; anti-inflammatory; asthma; brevenal; chemokine; cystic fibrosis; cytokine; immunomodulator; macrophage activation; macrophage phenotype; marine natural product; mucociliary clearance.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Aquatic Organisms / chemistry*
  • Cell Line, Tumor
  • Chronic Disease / therapy
  • Dinoflagellida / chemistry*
  • Drug Evaluation, Preclinical
  • Epithelial Cells / drug effects
  • Ethers / pharmacology*
  • Ethers / therapeutic use
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Lung / cytology
  • Macrophages / drug effects
  • Mice
  • Polymers / pharmacology*
  • Polymers / therapeutic use
  • Respiratory Mucosa / cytology
  • Respiratory Tract Diseases / drug therapy
  • Respiratory Tract Diseases / immunology


  • Anti-Inflammatory Agents
  • Ethers
  • Immunologic Factors
  • Polymers
  • brevenal (polyether)