Ginger and many other natural compounds have anti-inflammatory properties, making them popular supplements for those with inflammatory conditions. However, the method of action isn’t always well understood.
To identify how ACA can help block inflammation, researchers from Nara Institute of Science and Technology (NAIST) put 1'-acetoxychavicol acetate, or ACA, under the microscope. The compound comes from a plant the researchers characterized as 'tropical ginger Alpinia species'. The research was published in International Immunology.
The study
The research team found that ACA mitigates mitochondrial damage by decreasing mitochondrial reactive oxygen species (ROS). This blocks activation of a multiprotein complex known as the nucleotide-binding oligomerization. Many inflammatory conditions display improper and chronic activation of this protein complex.
“The nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing (NLRP) 3 inflammasome is a multiprotein complex that triggers Caspase-1-mediated IL-1β production and pyroptosis, and its dysregulation is associated with the pathogenesis of inflammatory diseases,” explained the authors.
By growing immune cells in culture from mouse bone marrow, and also using a mouse model of colitis, researchers added ACA to the growing cells. The live mice were given the compound in their food. From there, the researchers then examined the effects on ROS production, secretion of IL-1β, and other inflammation markers.
“Promising results”
The team found that ACA ameliorates mitochondrial damage, leading to the suppression of NLRP3-inflammasome activity and subsequent IL-1β release.
"Cells treated with ACA had significantly reduced IL-1β production, as well as lower levels of ROS," explains Taro Kawai, senior author. "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 be therapeutic for those with inflammatory conditions. "Interestingly, we did not observe high levels of immune cell death when using ACA, which means that it may be relatively safe," added Ori.
Background
Previous work has suggested that the NLRP3 inflammasome plays a crucial role in promoting inflammation by secreting the molecule IL-1β. This acts as a messenger that recruits various immune cells to the site of injury or infection. Additional studies described how production of ROS can help trigger activation of the NLRP3 inflammasome. Because other groups showed that ACA can reduce ROS production in certain immune cells, the NAIST researchers became curious how this compound would impact the NLRP3 inflammasome and its functions.
"Many disease pathogeneses involve dysregulation of the inflammasome," noted 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 authors conclude that this research demonstrates how ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory conditions and highlights the compound's potential for therapeutic use in conditions mediated by IL-1β molecules.
Source: International Immunology
dxab016, doi.org/10.1093/intimm/dxab016
“1′-acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression”
Authors: S.Sok et al.
