Abstract
Moringa oleifera Lamarck is commonly consumed for nutritional or medicinal properties. We recently reported the isolation and structure elucidation of novel bioactive phenolic glycosides, including 4-[(2'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate (RBITC), which was found to suppress inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 mouse macrophage cells. Inhibitors of proteins such as cyclooxygenase-2 (COX-2) and iNOS are potential antiinflammatory and cancer chemopreventive agents. The inhibitory activity of RBITC on NO production (IC(50) = 0.96 ± 0.23 μM) was greater than that mediated by other well-known isothiocyanates such as sulforaphane (IC(50) = 2.86 ± 0.39 μM) and benzyl isothiocyanate (IC(50) = 2.08 ± 0.28 μM). RBITC inhibited expression of COX-2 and iNOS at both the protein and mRNA levels. Major upstream signaling pathways involved mitogen-activated protein kinases and nuclear factor-κB (NF-κB). RBITC inhibited phosphorylation of extracellular signal-regulated kinase and stress-activated protein kinase, as well as ubiquitin-dependent degradation of inhibitor κBα (IκBα). In accordance with IκBα degradation, nuclear accumulation of NF-κB and subsequent binding to NF-κB cis-acting element was attenuated by treatment with RBITC. These data suggest RBITC should be included in the dietary armamentarium of isothiocyanates potentially capable of mediating antiinflammatory or cancer chemopreventive activity.