Citrulline cooperatively exerts an anti-inflammatory effect on synovial cells with glucosamine and N-acetylglucosamine.

The aim of the present study was to evaluate the anti-inflammatory effects of citrulline (Cit), glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) on synovial cells, which are primarily involved in inflammatory joint diseases. The combined effect of Cit, GlcN and GlcNAc on synovial cell inflammation was assessed by measuring IL-1β-induced IL-6 production. GlcN and GlcNAc (0.5 mM each) alone did not suppress IL-6 production, whereas Cit (0.5 mM) did significantly suppress IL-6 production. Furthermore, the combined effect of Cit, GlcNAc and GlcN was examined; Cit + GlcN and Cit + GlcNAc significantly suppressed not only IL-6 production, but also phosphorylation of ERK1/2. Similarly, combination of GlcN + GlcNAc significantly suppressed IL-6 production and phosphorylation of ERK1/2. These observations suggest that among Cit, GlcNAc and GlcN, the combination of Cit with GlcN or GlcNAc exerts a synergistic anti-inflammatory effect on synovial cells, thereby possibly exhibiting chondroprotective effects and alleviating inflammatory joint diseases.