Chikusetsusaponin V Inhibits LPS-Activated Inflammatory Responses via SIRT1/NF-κB Signaling Pathway in RAW264.7 Cells

Abstract

It is becoming increasingly accepted that macrophage activation play a crucial role in many diseases associated with chronic inflammation, such as metabolic disease, including atherosclerosis, obesity, and diabetes. Recent studies have indicated that the regulation of inflammation and energy metabolism are connected together through an antagonistic crosstalk between NF-κB and SIRT1 signaling pathways. In order to investigate anti-inflammatory drugs, we investigated whether SIRT1 is implicated in the lipopolysaccharide (LPS)-stimulated NF-κB signaling pathway in macrophage RAW264.7 cells when pretreated with chikusetsusaponin V (CsV). Griess assay and enzyme-linked immunosorbent assay were used to determine the effect of CsV on LPS-induced inflammatory cytokine secretion. Western blot was used to assess the effect of CsV on LPS-induced SIRT1 and Ac-NF-κB p65 expression. Results showed that CsV suppressed LPS-induced inflammatory cytokine NO, TNF-α, and IL-1β production in RAW264.7 cells. In addition, downregulation of SIRT1 and upregulation of Ac-NF-κB p65 induced by LPS were abolished by CsV in a dose-dependent manner in RAW264.7 cells. Meanwhile, inflammatory cytokines were regulated with CsV through SIRT1-Ac-NF-κB p65 signaling pathway. Therefore, our results demonstrate that CsV exerts an anti-inflammatory effect partly through SIRT1/NF-κB signaling pathways and SIRT1 may be a new target for anti-inflammation therapies.

Keywords: IL-1β; RAW264.7 cells; SIRT1; TNF-α; acetylated-NF-κB (ac-NF-κB); chikusetsusaponin V; inflammation.