The New research was published in the December 2014 issue of the Journal of Leukocyte Biology.
"Identification of small compounds that inhibit the NLRP3 inflammasome is required to design effective therapeutics," said Kiyoshi Takatsu, Ph.D., a researcher involved in the work from the Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research at the University of Toyama in Toyama Japan. "We hope that our findings will provide new information and strategy that can be exploited for development of new herbal medication of those diseases."
To make this find, scientists stimulated mouse macrophages with different inflammasome activators in the presence of isoliquiritigenin. Then, activation of NLRP3 inflammasome was examined by measuring IL-1beta production in the culture supernatants. Results showed that relatively low concentrations of isoliquiritigenin were highly effective in inhibiting IL-1beta production compared with known NLRP3 inflammasome inhibitors, such as parthenolide and sulfonylurea drug glyburide. For animal studies, three groups of mice were used. The first group of mice was fed a normal diet and the second group of mice was fed a high-fat diet. The third group of mice was fed a high-fat diet supplemented with 0.5 percent isoliquiritigenin. High-fat diet feeding for 20 weeks induced obesity, type 2 diabetes and hepatic steatosis in mice, but supplementation of ILG markedly improved these disorders. Finally, supplementation of isoliquiritigenin inhibited high-fat diet-induced IL-1beta production in adipose tissue.
"Obesity and associated metabolic disorders are one of the most important emerging medical conditions. Recent work demonstrates a critical role for obesity-driven inflammation in a multitude of medical problems arising from obesity with a central role for the inflammasome," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology
. "This new work not only identifies a novel class of potential inflammasome inhibitors, but also demonstrates effectiveness in a preclinical model of obesity induced disease."