Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

Molecules. 2018 Feb 24;23(2):506. doi: 10.3390/molecules23020506.


Age-related diseases, such as osteoarthritis, Alzheimer's disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.

Keywords: 5-lipoxygenase; boswellic acid; cathepsin; frankincense; microsomal prostaglandin E2 synthase; triterpene acid.

MeSH terms

  • Arachidonate 5-Lipoxygenase / metabolism
  • Cathepsin G / antagonists & inhibitors*
  • Enzyme Activation / drug effects
  • Frankincense / chemistry*
  • Lipoxygenase Inhibitors / chemical synthesis
  • Lipoxygenase Inhibitors / chemistry*
  • Lipoxygenase Inhibitors / isolation & purification
  • Lipoxygenase Inhibitors / pharmacology*
  • Plant Extracts / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry*
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*


  • Lipoxygenase Inhibitors
  • Plant Extracts
  • Triterpenes
  • boswellic acid
  • Arachidonate 5-Lipoxygenase
  • Cathepsin G
  • Frankincense