Abstract
Several studies have reported that metal complexes exhibit anti-inflammatory activities; however, the molecular mechanism is not well understood. In this study, we used a potent ruthenium (II)-derived compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), to investigate the molecular mechanisms underlying the anti-inflammatory effects against lipopolysaccharide (LPS)-induced macrophage activation and liver injury in mice. Treating LPS-stimulated RAW 264.7 cells with TQ-6 suppressed nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. The LPS-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were reduced in TQ-6-treated cells. TQ-6 suppressed, LPS-stimulated p38 MAPK phosphorylation, IκBα degradation, and p65 nuclear translocation in cells. Consistent with the in vitro studies, TQ-6 also suppressed the expression of iNOS, TNF-α, and p65 in the mouse model with acute liver injury induced by LPS. The present study showed that TQ-6 could protect against LPS-induced in vitro inflammation in macrophage and in vivo liver injury in mice, and suggested that NF-κB could be a promising target for protecting against LPS-induced inflammation and liver injury by TQ-6. Therefore, TQ-6 can be a potential therapeutic agent for treating inflammatory diseases.
Highlights
Inflammation is a complex process mediated by the activation of inflammatory and immune cells
Metal complexes possess several notable advantages that render them as attractive alternatives to organic small molecules for the development of therapeutic agents [9]
Relatively less attention has been devoted to the development of metal complexes for anti-inflammatory applications
Summary
Inflammation is a complex process mediated by the activation of inflammatory and immune cells. LPS is an active pathogen-related molecular agent and a cell wall component of gram-negative bacteria. Subsequent to stimulation with LPS, NF-κB is activated by the inhibitor of the κB (IκB)-kinase (IKK) complex [4]. The liberated dimeric NF-κB (p65 and p50 subunits) translocates to the nucleus and activates the transcription of pro-inflammatory target genes that encode regulatory proteins. This leads to physiological responses, including inflammatory or immune responses [4]
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