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Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells

  • Authors:
    • Jie Zhu
    • Chengqun Luo
    • Ping Wang
    • Quanyong He
    • Jianda Zhou
    • Hao Peng

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  • Published online on: March 4, 2013     https://doi.org/10.3892/etm.2013.988
  • Pages: 1345-1350
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Abstract

Saikosaponin A (SSA) is a major triterpenoid saponin isolated from Radix bupleuri (RB), a widely used Chinese traditional medicine to treat various inflammation-related diseases. The aim of this study was to investigate the anti-inflammatory activity, as well as the molecular mechanism of SSA in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In this study, we demonstrated that SSA markedly inhibits the expression of certain immune-related cytotoxic factors, including cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS), as well as pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. It also significantly upregulates the expression of IL-10, an important anti-inflammatory cytokine, suggesting its anti-inflammatory activity in LPS-stimulated macrophages. We further demonstrated that SSA inhibits the activation of the nuclear factor-κB (NF-κB) signaling pathway by suppressing the phosphorylation of inhibitory NF-κB inhibitor α (IκBα) and thus holding p65 NF-κB in the cytoplasm to prevent its translocation to the nucleus. In addition, SSA also inhibits the mitogen-activated protein kinase (MAPK) signaling pathway by downregulating the phosphorylation of p38 MAPK, c-Jun N-terminal kinase (c-JNK) and extracellular signal-regulated kinase (ERK), the three key components of the MAPK family. In conclusion, our study demonstrates that SSA has an anti-inflammatory effect by regulating inflammatory mediators and suppressing the MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 cells.
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May 2013
Volume 5 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhu J, Luo C, Wang P, He Q, Zhou J and Peng H: Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells. Exp Ther Med 5: 1345-1350, 2013
APA
Zhu, J., Luo, C., Wang, P., He, Q., Zhou, J., & Peng, H. (2013). Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells. Experimental and Therapeutic Medicine, 5, 1345-1350. https://doi.org/10.3892/etm.2013.988
MLA
Zhu, J., Luo, C., Wang, P., He, Q., Zhou, J., Peng, H."Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells". Experimental and Therapeutic Medicine 5.5 (2013): 1345-1350.
Chicago
Zhu, J., Luo, C., Wang, P., He, Q., Zhou, J., Peng, H."Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells". Experimental and Therapeutic Medicine 5, no. 5 (2013): 1345-1350. https://doi.org/10.3892/etm.2013.988