Effects of Gambogic Acid on the Production of Reactive Oxygen Species and Neutrophil Extracellular Traps

Abstract

The innate immune system responds rapidly to the early signs of an infection or tissue damage by recruiting neutrophils to the affected area, where these inflammatory cells kill microbes through the production of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Although these normal inflammatory responses are necessary for the elimination of potential pathogens before they proliferate and establish an infection, ROS and NETs are non‐specific mechanisms that can also damage host tissues. In chronic inflammation associated with various diseases, such as rheumatoid arthritis or Crohn's disease, prolonged or non‐resolving inflammation can cause severe pain and permanent tissue damage. We are currently investigating the potential of gambogic acid, a compound derived from the Garcinia hanburyi plant used in Ayurvedic and traditional Thai medicines, to reduce inflammation or promote its resolution. Previous studies have suggested that gambogic acid promotes apoptosis in multiple cell types, suggesting that this molecule could promote neutrophil apoptosis and thereby inhibit their inflammatory functions. In support of this hypothesis, we found that gambogic acid decreases PMA‐induced ROS and NETs by neutrophil‐like HL‐60 cells. Gambogic acid also decreases survival of neutrophil‐like HL‐60 cells in a WST‐8 survival assay, suggesting that it may reduce pro‐inflammatory neutrophil functions by inducing their apoptosis. We are currently investigating whether gambogic acid exerts similar effects on NET and ROS production in normal human polymorphonuclear cells (PMNs), and whether the gambogic acid impacts on neutrophil function are dependent upon its induction of neutrophil apoptosis. If so, this would suggest a therapeutic, inflammation‐resolving potential of gambogic acid in diseases characterized by excessive inflammation.Support or Funding InformationDePauw University, Science Research FellowsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.