Schisantherin A Exhibits Anti-inflammatory Properties by Down-Regulating NF-κB and MAPK Signaling Pathways in Lipopolysaccharide-Treated RAW 264.7 Cells

• DOI: 10.1007/s10753-009-9166-7
• Publication Date: 2009-11-13T09:54:56Z
• Authors: Xinxin Ci; Rong Ren; Kan Xu; Hongyu Li; Qinlei Yu; Yu Song; Dacheng Wang; Rongtao Li; Xuming Deng
• Keywords: Lipopolysaccharides; 0301 basic medicine; Dose-Response Relationship, Drug; Cell Survival; Interleukin-6; MAP Kinase Signaling System; Macrophages; Anti-Inflammatory Agents; JNK Mitogen-Activated Protein Kinases; NF-kappa B; Dioxoles; Dinoprostone; Lignans; Cell Line; I-kappa B Kinase; 3. Good health; Cyclooctanes; Mice; 03 medical and health sciences; Cyclooxygenase 2; Animals; Inflammation Mediators; Extracellular Signal-Regulated MAP Kinases

Schisantherin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent under the name of Wuweizi in Chinese traditional medicine. In the present study, we carry out a screening program to identify the anti-inflammatory potentials of schisantherin A. We found that schisantherin A reduced lipopolysaccharide (LPS (1 mg/L))-induced levels of TNF-alpha, IL-6, NO, and PGE2 (p<0.01 or p<0.05), and also reduced levels of iNOS and COX-2 in RAW 264.7 macrophages in a concentration-dependent manner. We further investigated signal transduction mechanisms to determine how schisantherin A affects. RAW264.7 cells were pretreated with 0.5, 2.5, or 25 mg/L of schisantherin A 1 h prior to treatment with 1 mg/L of LPS. Thirty minutes later, cells were harvested and mitogen activated protein kinases (MAPKs) activation and I kappaB alpha was measured by Western blot. Alternatively, cells were fixed and nuclear factor-kappaB (NF-kappaB) activation was measured using immunocytochemical analysis. Signal transduction studies showed that schisantherin A significantly inhibited extracellular signal-regulated kinase (ERK), p38, and c-jun NH2-terminal kinase (JNK) phosphorylation protein expression. Schisantherin A also inhibited p65-NF-kappaB translocation into the nucleus by I kappaB alpha degradation. By using specific inhibitors of ERK, JNK and p38, we found that schisantherin A may inhibit TNF-alpha mostly through ERK pathway. Therefore, schisantherin A may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kappaB and MAPKs signaling in RAW264.7 cells.