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

Zhu,Jie; Luo,Chengqun; Wang,Ping; He,Quanyong; Zhou,Jianda; Peng,Hao

doi:10.3892/etm.2013.988

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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Affiliations: Department of Burns and Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Centre of PET-CT, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P.R. China
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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