, Volume 42, Issue 6, pp 2192–2204 | Cite as

6-Bromoindirubin-3′-Oxime Suppresses LPS-Induced Inflammation via Inhibition of the TLR4/NF-κB and TLR4/MAPK Signaling Pathways

  • Chang Liu
  • Xin Tang
  • Wenjing Zhang
  • Guohong Li
  • Yingyu Chen
  • Aizhen Guo
  • Changmin HuEmail author
Original Article


We investigated the efficacy of the traditional herbal extract 6-bromoindirubin-3′-oxime (BIO) against lipopolysaccharide (LPS)-induced mastitis in mice and inflammatory signaling in mouse mammary epithelial cells (MMECs). In vivo, breast inflammation scores and enzyme-linked immunosorbent assay (ELISA) detection of pro-inflammatory factor expression were used to assess the effect of BIO against mastitis. In vitro, the effects of BIO on LPS-induced changes in the expression levels of pro-inflammatory factors, anti-inflammatory cytokines, and signaling factors of the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and TLR4/mitogen-activated protein kinase (MAPK) pathways were examined by qRT-PCR and ELISA. In LPS-injected mice, BIO pretreatment downregulated the expression of the pro-inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) in mammary glands and reduced inflammatory lesions in breast tissue. In MMECs, BIO pretreatment downregulated the LPS-induced expression of IL-1β, IL-6, and TNF-α. Further, BIO inhibited both the expression and phosphorylation of TLR4/NF-κB and TLR4/MAPK signaling factors. Thus, BIO downregulates IL-6, IL-1β, TNF-α, and MPO expression, upregulates IL-10 expression, and suppresses LPS-induced inflammation by inhibiting the TLR4/NF-κB and TLR4/MAPK pathways. BIO may be a potential treatment agent for mastitis and other inflammatory diseases.


BIO lipopolysaccharide (LPS) TLR4 NF-κB MAPK inflammation 



We would like to thank all our coworkers in the State Key Laboratory of Agricultural Microbiology (Wuhan, China) for useful discussions. This work was supported by the National Key Research and Development Plan (No. 2016YFD0500906), and the special fund for the China Agriculture Research System (Beef/Yak cattle) (No. CARS-38), and the Research Fund for National Distinguished Scholars in Agriculture Research and Technical Innovative Team.

Compliance with Ethical Standards

Conflict of Interest

All co-authors implicated in this research approved this article to be published. The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chang Liu
    • 1
  • Xin Tang
    • 1
  • Wenjing Zhang
    • 1
  • Guohong Li
    • 1
  • Yingyu Chen
    • 1
  • Aizhen Guo
    • 1
    • 2
  • Changmin Hu
    • 1
    Email author
  1. 1.The Faculty of Veterinary MedicineHuazhong Agricultural UniversityWuhanChina
  2. 2.State Key Laboratory Agricultural MicrobiologyHuazhong Agricultural UniversityWuhanChina

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