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Bakuchicin alleviates ovalbumin-induced allergic asthma by regulating M2 macrophage polarization

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Abstract

Objective

Asthma is an airway inflammatory disease caused by activation of numerous immune cells including macrophages. Bakuchicin (BKC) is known to exhibit anti-inflammatory effects and type 2 T helper (Th2) regulation, but has not been investigated for airway inflammation. This study aimed to evaluate the effects of BKC on airway inflammation and demonstrate the mechanisms of macrophage polarization.

Methods

The anti-inflammatory effects were determined using lipopolysaccharide (LPS)-stimulated macrophages. The ovalbumin (OVA)-induced asthma mouse model was used to evaluate the effects of BKC on airway inflammation and Th2 responses. Moreover, the effect of BKC on macrophage polarization was confirmed in bone marrow-derived macrophages (BMDMs) differentiation.

Results

BKC suppressed nitric oxide production and expression of pro-inflammatory cytokines by inhibiting signaling pathway in LPS-stimulated macrophages. In an OVA-induced asthma model, BKC treatment alleviated histological changes and mast cell infiltration and reduced the levels of eosinophil peroxidase, β-hexosaminidase, and immunoglobulin levels. In addition, BKC alleviated Th2 responses and M2 macrophage populations in bronchoalveolar fluid. In BMDMs, BKC suppressed IL-4-induced M2 macrophage polarization and the expression of M2 markers such as arginase-1 and Fizz-1 through inhibiting sirtuin 2 levels.

Conclusion

BKC could be a drug candidate for the treatment of allergic asthma.

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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by KRIBB Research Initiative Program (KGM5242322) and the National Research Foundation of Korea grants funded by the Korean government (2022M3A9G8082645).

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Authors and Affiliations

  1. Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea

    Yeon-Yong Kim, Seungwon Jeong, Seung Woong Lee, Seung-Jae Lee, Mun-Chual Rho & Soyoung Lee

  2. Cell and Matrix Research Institute, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Yeon-Yong Kim & Sang-Hyun Kim

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Contributions

Y-YK and SJ performed data curation, formal analysis, methodology, validation, investigation, and visualization. SWL, S-JL, and M-CR participated in methodology, software, and validation. S-HK and SL contributed to the study conceptualization, supervision, project administration, resources, and funding acquisition. The original draft was written by Y-YK, and reviewed/edited by S-HK and SL. The final version of the manuscript was read and approved by all authors.

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Correspondence to Sang-Hyun Kim or Soyoung Lee.

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Kim, YY., Jeong, S., Lee, S.W. et al. Bakuchicin alleviates ovalbumin-induced allergic asthma by regulating M2 macrophage polarization. Inflamm. Res. (2024). https://doi.org/10.1007/s00011-024-01859-8

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