title: Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells.
abstract: Saikosaponin A (SSA) is a major triterpenoid saponin isolated fromRadix 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.
authors.affiliation: Department of Burns and Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Chengqun
authors.initials: C
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Quanyong
authors.initials: Q
authors.lastname: He
authors.forename: Jianda
authors.initials: J
authors.lastname: Zhou
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
keywords: inflammation; inflammatory cytokine; lipopolysaccharide; mitogen-activated protein kinase; nuclear factor-κB; saikosaponin A