Nuciferine attenuates lipopolysaccharide-stimulated inflammatory responses by inhibiting p38 MAPK/ATF2 signaling pathways

Nuciferine, isolated from Nelumbo nucifera (commonly known as lotus) leaves, has been shown to have beneficial effects, including antioxidant, anti-obesity, anti-diabetic, and anti-inflammatory properties. However, little is known about the mechanism of nuciferine action on the inflammatory response. This study aimed to investigate the anti-inflammatory effects of nuciferine and its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated murine macrophages. In this study, nuciferine reduced LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production and mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Nuciferine also decreased the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Furthermore, nuciferine inhibited the LPS-mediated transcriptional activity of nuclear factor (NF)-κB and activator protein (AP)-1, and the nuclear translocation of NF-κB p65 and activating transcription factor 2 (ATF2), an AP-1 subunit. Nuciferine also decreased the phosphorylation of IκB kinase (IKK), inhibitor of NF-κB (IκB), NF-κB, mitogen-activated protein kinase 3 (MKK3), MKK6, p38 mitogen-activated protein kinase (MAPK), and ATF2. Overall, our findings suggest that nuciferine may exert anti-inflammatory effects in LPS-induced macrophages by inhibiting the NF-κB and p38 MAPK/ATF2 signaling pathways.