Prenylated phenolic compounds from licorice (Glycyrrhiza uralensis) and their anti-inflammatory activity against osteoarthritis

Osteoarthritis is a significant driver of disability in the elderly with increasing prevalence, and inflammation plays a vital role on its etiology. Licorice is commonly used as a traditional Chinese medicine or food additive, and its prenylated phenolic compounds were recently reported to be able to inhibit osteoarthritis with anti-inflammatory activity. In order to explore more anti-osteoarthritic prenylated phenolic compounds from licorice, we isolated ten compounds (1-10), with three new ones (1-3), from the ethyl acetate extract of Glycyrrhiza uralensis. Compound 2 (glycyuralin R) was a racemic 3-phenoxy-chromanone, and we achieved its chiral separation for the first time. Compounds 1, 2, 7 and 8 showed significant NO inhibitory ability in IL-1β-stimulated mouse primary chondrocytes, and we further confirmed the anti-inflammatory activity of 1 (glycyuralin Q) by evaluating its effect on osteoarthritis-related iNOS, COX-2, TNF-α, IL-6, MMP3, MMP13 and NF-κB based on various experimental methods. These results clarified the potential of several prenylated phenolic compounds, especially 1 in licorice, as the lead compounds for osteoarthritis.