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

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Abstract

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.

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ACKNOWLEDGMENTS

We are grateful to Key Laboratory of Tibetan medicine research, Chinese Academy of Sciences for the use of shared facilities.

Funding

This project was supported by the Science and Technology of Qinghai Province (2019-ZJ-7082) and National Natural Science Foundation of China (no. 31701243).

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Authors and Affiliations

  1. Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Qinghai, Xining, 810001, China

    Weidong Wang, Jing Zhang, Zenggen Liu, Yunhe Zhu, Lijuan Mei, Yanduo Tao & Lei Jiang

  2. Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Qinghai, Xining, 810017, China

    Weidong Wang, Jing Zhang, Zenggen Liu, Yunhe Zhu, Lijuan Mei, Yanduo Tao & Lei Jiang

  3. University of Chinese Academy of Science, Beijing, 101408, China

    Weidong Wang, Jing Zhang & Yunhe Zhu

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  1. Weidong Wang
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Correspondence to Lei Jiang.

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This article does not contain any studies involving human participants performed by any of the authors and does not contain any studies involving animals performed by any of the authors.

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Abbreviations: XT, Xanthotoxol; LPS, lipopolysaccharides; TNF-α, tumor necrosis factor-α; NO, nitric oxide; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor-κB; IL-1β, interleukin-1β; IL-6, interleukin-6; NFAT1, Nuclear Factor of Activated T-Cells1.

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Weidong Wang, Zhang, J., Liu, Z. et al. Xanthotoxol from Saussurea obvallata Attenuates LPS-Induced RAW 264.7 Cells Inflammatory Responses through NF-κB Pathway. Russ J Bioorg Chem 48, 300–309 (2022). https://doi.org/10.1134/S1068162022020248

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