Steroidal alkaloid solanine A from Solanum nigrum Linn. exhibits anti-inflammatory activity in lipopolysaccharide/interferon gamma-activated murine macrophages and animal models of inflammation

摘要

Solanine A is a novel steroidal alkaloid isolated from Solarium 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 E-2 (PGE(2)) in lipopolysaccharide/interferon-gamma (LPS/IFN gamma)-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-alpha (TNF-alpha), interleukin-6 (IL-6), and -1 beta (IL-1 beta), as well as C-X-C motif chemokine ligand-9 (CXCL9), were significantly decreased by solanine A. Furthermore, solanine A also suppressed LPS/IFN gamma-induced protein expression of iNOS and COX2. Mechanistically, solanine A inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) through the prevention of NF-kappa B p65 and inhibitory kappa B-alpha (I kappa B alpha) phosphorylation and I kappa B alpha 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/IFN gamma-stimulated RAW264.7 macrophages and agar-induced granuloma model in mice. Taken together, solanine A exhibits a potent antiinflammatory activity in LPS/IFN gamma- activated macrophages and animal models of inflammation through inhibition of NF-kappa B, ERK1/2, Akt and STAT1 signaling pathways, suggesting that solanine A may be a valuable leading compound in the treatment of inflammatory diseases.