New research has shown how compound found in the tropical ginger plant, 1′-acetoxychavicol acetate, or ACA, can have an anti-inflammatory effect.
Researchers found that ACA reduces mitochondrial damage by lowering levels of mitochondrial reactive oxygen species (ROS), blocking activation of a crucial protein complex known as the NLRP3 inflammasome. A number of inflammatory diseases, like inflammatory bowel disease, display improper and chronic activation of this complex.
It has been suggested by previous studies that the NLRP3 inflammasome plays a significant role in promoting inflammation by secreting a molecule called IL-1β. This molecule works as a messenger, sending various immune cells to the site of injury or infection. Further studies detailed how production of ROS can help to trigger the NLRP3 inflammasome. Because other groups showed that the ginger compound ACA can reduce ROS production in certain immune cells, the researchers wondered how this compound would affect the way NLRP3 inflammasome worked.
“Many disease pathogeneses involve dysregulation of the inflammasome,” commented Daisuke Ori, co-lead author on the study. “Blood cells from people suffering from rheumatoid arthritis or other autoimmune disorders frequently have increased levels of inflammasome-derived IL-1β. Therefore, targeting the NLRP3 inflammasome with a compound like ACA may be a promising therapeutic strategy.”
The researchers took immune cells from mouse bone marrow, and also used a mouse model of colitis. ACA was added to the growing cells and the compound was added to their mice’s food. The researchers then looked at the effects on ROS production, secretion of IL-1β, and other markers of inflammation.
“Cells treated with ACA had significantly reduced IL-1β production, as well as lower levels of ROS,” explained senior author Taro Kawai. “ACA could also inhibit NLRP3 inflammasome activation in the colitis mouse model.” These in vivo results are promising, as they suggest ACA has the potential to treat or prevent the development of inflammatory diseases. “Interestingly, we did not observe high levels of immune cell death when using ACA, which means that it may be relatively safe,” continued Ori.
The study provided novel evidence for a specific molecular mechanism governing the previously observed anti-inflammatory properties of ACA. The study also showed the potential of ACA for therapeutic use in diseases mediated by IL-1β molecules, or associated with cytokine storms, as seen in patients suffering from severe COVID.
Source: Medical Xpress
Journal information: Sophia P M Sok et al. 1′-acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression, International Immunology (2021). DOI: 10.1093/intimm/dxab016
