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

• Published in: Toxicology in vitro Vol. 26; no. 1; pp. 1 - 6
• Main Authors: Gao, Yonglin, Jiang, Wanglin, Dong, Chaohua, Li, Chunmei, Fu, Xuejun, Min, Li, Tian, Jingwei, Jin, Haizhu, Shen, Jingyu
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2012
• Subjects: Alkaloids; Alkaloids - pharmacology; Animals; Anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Cell Line; Cell Survival - drug effects; COX-2; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; I-kappa B Proteins - metabolism; iNOS; Interleukin-6 - metabolism; L-Lactate Dehydrogenase - metabolism; Lipopolysaccharides; Mice; Mitogen-activated protein kinases; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; NF-κB; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Signal Transduction - drug effects; Sophocarpine; Sophora alopecuroides; Tumor Necrosis Factor-alpha - metabolism; Erk1/2; RFU; Cmax; COX-2; JNK; IL-6; LPS; IκB; LDH; NF-κB; Sophocarpine; iNOS; Anti-inflammatory activity; MAPKs; Mitogen-activated protein kinases
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2011.09.019

► Sophocarpine inhibits the production of TNF-α and IL-6 in RAW 264.7 cells. ► Sophocarpine inhibited the production of iNOS and COX-2 expression in RAW 264.7 cells. ► Anti-inflammatory mechanisms of sophocarpine via NF-κB and MAPKs inactivation. 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 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-κB activation.