Solanine A is a novel steroidal alkaloid isolated from Solanum nigrum Linn., a medicinal and edible plant which is widely used for treating various inflammatory diseases. In this study, we found that solanine A markedly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide/interferon-γ (LPS/IFNγ)-stimulated RAW264.7 cells, and attenuated xylene, carrageenan and agar-induced inflammation in mice. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β), as well as C-X-C motif chemokine ligand-9 (CXCL9), were significantly decreased by solanine A. Furthermore, solanine A also suppressed LPS/IFNγ-induced protein expression of iNOS and COX2. Mechanistically, solanine A inhibited the nuclear translocation of nuclear factor-κB (NF-κB) through the prevention of NF-κB p65 and inhibitory κB-α (IκBα) phosphorylation and IκBα degradation, and it also suppressed activation of extracellular regulated protein kinases (ERK), signal transducers and activators of transcription-1 (STAT1) and serine/threonine protein kinase Akt in LPS/IFNγ-stimulated RAW264.7 macrophages and agar-induced granuloma model in mice. Taken together, solanine A exhibits a potent anti-inflammatory activity in LPS/IFNγ- activated macrophages and animal models of inflammation through inhibition of NF-κB, ERK1/2, Akt and STAT1 signaling pathways, suggesting that solanine A may be a valuable leading compound in the treatment of inflammatory diseases. Copyright © 2018 Elsevier Masson SAS. All rights reserved.