The primary toxic component of fire ant venom reduced skin thickening and inflammation in mouse models of psoriasis, and could lead to new treatment options in humans.
 
Solenopsin A is a venom alkaloid from the fire ant that chemically resembles ceramides. These lipid-like molecules are found in many skin care products and are essential for maintaining the barrier function of the skin.
 
However, ceramides can behave as a double-edged sword. Under certain conditions, ceramides can be converted by cells into the inflammatory molecule sphingosine-1-phosphate (S1P).
 
In a study published in Scientific Reports, investigators synthesized solenopsin analogs that biochemically act as ceramides, but cannot be metabolized to S1P.
 
A 1% skin cream containing the compounds was applied to a mouse model for 28 days. Mice treated with solenopsin analogs experienced decreases in skin thickness by approximately 30% compared with the controls.
 
The treated mice also had approximately 50% less immune cells infiltrating the skin. When applied to the immune cells in culture, the findings showed the compounds decreased production of the cells’ inflammatory signal IL-22 and increased production of anti-inflammatory IL-12.
 
“We believe that solenopsin analogs are contributing to full restoration of the barrier function in the skin,” said lead author Jack Arbiser, MD, PhD. “Emollients can soothe the skin in psoriasis, but they are not sufficient for restoration of the barrier.”
 
The investigators also examined how gene activity patterns changed in the skins of mice after treatment, and found solenopsin analogs downregulated TLR4 expression in keratinocytes.
 
“This may be compensatory and a mechanism of resistance to anti-psoriasis therapy, and it suggest that the solenopsin compounds could be used in combination with existing approaches,” Arbiser said.
 
The findings suggest barrier restoration has both a biochemical and physical component, and both are needed for optimal barrier restoration, the authors noted. They added that further studies of these analogs as anti-psoriatic drugs are needed.