Abstract:
Tert-butyl 2-((5-methylfuran-2-yl)(4-nitrophenyl)-1H-pyrrole-1-carboxylate orJJSRUN is a novel synthetic derivative of asymmetrical triarylmethane. In the present study, JJSRUN16 was investigated the mechanism underlying its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that JJSRAN16 potently reduced inducible nitric oxide (NO) production, expression of mRNA and protein of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Production of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) expression were not effected by JJSRUN16. Also, the compound did not decrease the expression of COX-1 gene. JJSRUN16 inhibited nuclear translocation of NF-KB p65 subunit into the nucleus. Furthermore, JJSRUN16 significantly decreased phosphorylation ofc-Jun N-terminal kinases (JNKs) and p38-mitogen activated protein kinase (p38-MAPK) but not extracellular signal-regulated kinases (ERKs). Taken together, our data suggest that JJSRUN16 suppresses LPS-stimilated inflammatory response by inhibition of NO production through inhibition of the JNK/p38 MAPK and NF-KB signaling pathways.