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Saikosaponin B2 Suppresses Inflammatory Responses Through IKK/IκBα/NF-κB Signaling Inactivation in LPS-Induced RAW 264.7 Macrophages

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Abstract

Bupleurum falcatum (Umbelliferae) have been widely used to treat inflammatory diseases as traditional medicines in East Asian region. Although saikosaponins are main bioactive molecules of B. falcatum, there is little information on bioactivity of saikosaponin B2 (SSB2). This study was conducted to assess the anti-inflammatory activities and the involved mechanisms of SSB2 in LPS-induced RAW 264.7 macrophages. SSB2 suppressed the releases of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukins (IL)-6, and IL-1β by suppressing mRNA levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, and IL-6 in LPS-induced macrophages. SSB2 blocked LPS-induced DNA binding and nuclear factor kappa B (NF-κB) transcriptional activity by inhibiting nuclear translocation p65 and p50, inhibitory κBα (IκBα) degradation, and IκB kinase β (IKKβ) phosphorylation and activity. In IKKβ-overexpressing cells, SSB2 significantly suppressed IKKβ-dependent NF-κB transcriptional activity. Moreover, SSB2 reduced phosphorylation of p38 and extracellular signal-regulated kinase1/2 (ERK1/2). SSB2 effectively inhibits LPS-induced pro-inflammatory mediator releases by interfering with IKKβ and IκBα activation, thus preventing NF-κB activation. Our data indicates that SSB2 could be a potential therapeutic application for inflammation-associated diseases.

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Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017R1A5A2014768) and supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1A6A3A11031647).

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Author notes

  1. Authors Ji-Sun Shin and Ho-Taek Im contributed equally to this work as co-first authors.

Authors and Affiliations

  1. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Dongdaemun-Ku, Kyungheedae-ro 26, Seoul, 02447, Republic of Korea

    Ji-Sun Shin, Ho-Taek Im & Kyung-Tae Lee

  2. Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyungheedae-ro 26, Seoul, 02447, Republic of Korea

    Kyung-Tae Lee

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  1. Ji-Sun Shin
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Correspondence to Kyung-Tae Lee.

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Shin, JS., Im, HT. & Lee, KT. Saikosaponin B2 Suppresses Inflammatory Responses Through IKK/IκBα/NF-κB Signaling Inactivation in LPS-Induced RAW 264.7 Macrophages. Inflammation 42, 342–353 (2019). https://doi.org/10.1007/s10753-018-0898-0

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