Xanthotoxol from Saussurea obvallata Attenuates LPS-Induced RAW 264.7 Cells Inflammatory Responses through NF-κB Pathway

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Saussurea obvallata has been used as a medicinal herb to treat rheumatoid arthritis in Qinghai-Tibet Plateau. Xanthotoxol, one of the major ingredients of S. obvallata, displays anti-inflammation bioactivities according to previous studies. However, the underlying mechanism of xanthotoxol in anti-inflammation have not yet been elucidated. In this study, XT was isolated from S. obvallata for the first time and we investigated the anti-inflammatory activity and the related molecular mechanism in LPS-activated macrophages in vitro model. The cytotoxicity of XT was determined through MTT assay and flow cytometry analysis. The anti-inflammatory activities of XT were determined according to its inhibitory effects on NO, and αpro-inflammatory cytokines. The date showed that XT significantly reduced inflammatory cytokines TNF-α, IL-6, and IL-1β in LPS-induced RAW264.7 cells as well as the synthesis of NO in a dose dependent manner. Moreover, xanthotoxol down-regulated the phosphorylation of NF-κB factors (p-P65, p-IκBα, p‑IKKα/β), the expressions of INOS and NFAT1 and the P65 translocation from the cytoplasm to the nucleus. These results suggested that XT exhibited significant anti-inflammatory activity in LPS-induced RAW264.7 cells model by inhibiting NF-κB pathway. These results might provide some explanations of the anti-inflammatory activity of S. obvallata and contribute to the further investigation and application of XT as a potential anti-inflammatory drug.