Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways

Toxicol In Vitro. 2012 Feb;26(1):1-6. doi: 10.1016/j.tiv.2011.09.019. Epub 2011 Sep 29.


Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Our previous studies have showed that sophocarpine exerts anti-inflammatory activity in animal models. In the present study, anti-inflammatory mechanisms of sophocarpine were investigated in lipopolysaccharide (LPS)-induced responses in RAW 264.7 cells. Furthermore, the cytotoxicity of sophocarpine was tested. The results indicated that sophocarpine could increase the LDH level and inhibit cell viability up to 800μg/ml, and which was far higher than that of the plasma concentration of sophocarpine in clinical effective dosage. The results also demonstrated that sophocarpine (50 and 100μg/ml) suppressed LPS-stimulated NO production and pro-inflammatory cytokines secretion, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). These were associated with the decrease of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, sophocarpine inhibited LPS-mediated nuclear factor-κB (NF-κB) activation via the prevention of inhibitor κB (IκB) phosphorylation. Sophocarpine had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), whereas it attenuated the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun NH(2)-terminal kinase (JNK). Our data suggested that sophocarpine exerted anti-inflammatory activity in vitro, and it might attribute to the inhibition of iNOS and COX-2 expressions via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-κB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • I-kappa B Proteins / metabolism
  • Interleukin-6 / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lipopolysaccharides
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Alkaloids
  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • I-kappa B Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Nfkbia protein, mouse
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • sophocarpine
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases