期刊
TOXICOLOGY IN VITRO
卷 26, 期 1, 页码 1-6出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2011.09.019
关键词
Sophocarpine; Anti-inflammatory activity; iNOS; COX-2; NF-kappa B; Mitogen-activated protein kinases
类别
资金
- Natural Science Foundation of Shandong Province [ZR2010HQ024]
- National Natural Science Foundation of China [81001661]
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 800 mu g/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 100 mu g/ml) suppressed LPS-stimulated NO production and pro-inflammatory cytokines secretion, including tumor necrosis factor alpha (TNF-alpha) 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-kappa B (NF-kappa B) activation via the prevention of inhibitor kappa B (I kappa B) 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 NH2-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-kappa B activation. (C) 2011 Elsevier Ltd. All rights reserved.
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