Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, the author is Fu, Yong and a compound is mentioned, 108-47-4, 2,4-Dimethylpyridine, introducing its new discovery. 108-47-4
A novel pyrazole-containing indolizine derivative suppresses NF-kappaB activation and protects against TNBS-induced colitis via a PPAR-gamma-dependent pathway
The nuclear factor-kappaB (NF-kappaB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn’s disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-kappaB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-gamma and inhibit the NF-kappaB pathway in colonic macrophages holds great promise for the treatment of CD. In this study, five novel pyrazole-containing indolizine derivatives (B1, B2, B3, B4 and B5) were successfully synthesized and characterized, and their anti-inflammatory activities for CD treatment were also investigated. Among the five compounds, compound B4 effectively decreased the NF-kappaB-mediated production of the pro-inflammatory cytokine TNF-alpha in LPS-stimulated peritoneal macrophages. Moreover, compound B4 significantly ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis symptoms, including body weight loss, colonic pathological damage and inflammatory cell infiltration. The results of western blotting and luciferase reporter assays indicated that compound B4 activated PPAR-gamma and subsequently suppressed NF-kappaB activation. Conversely, the addition of the PPAR-gamma antagonist GW9662 abrogated the anti-inflammatory effects of compound B4 both in vitro and in vivo. In summary, compound B4 activated the PPAR-gamma pathway to inhibit downstream NF-kappaB signaling, which alleviated experimental colitis. Thus, this compound may serve as a potential therapeutic agent for patients with CD.
Interested yet? Keep reading other articles of 4265-16-1!, 108-47-4
Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis