Anti-inflammatory effect of aqueous extract from Kawachi-bankan (Citrus maxima) peel in vitro and in vivo

  • Momoko Ishida
  • Chihiro Takekuni
  • Kosuke Nishi
  • Takuya SugaharaEmail author
Original Article


Kawachi-bankan (Citrus maxima) is one of the citruses produced in Ehime, Japan. Although health functions of flavonoids and carotenoids in citrus peel have been studied very well, those of water-soluble substances in the peel have not been focused. We herein indicated the anti-inflammatory effect of Kawachi-bankan peel aqueous extract (KPE) in vitro and in vivo. KPE significantly inhibited the production of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α by LPS-stimulated RAW264.7 cells without cytotoxicity. KPE also significantly inhibited the mRNA expression levels of IL-6 and TNF-α in the cells, suggesting that KPE inhibits the production of inflammatory cytokines by suppressing the gene expression levels. Immunoblot analysis revealed that KPE shows an anti-inflammatory effect on macrophages through the suppression of the phosphorylation of p38 and the translocation of NF-κB into nucleus. The oral administration of KPE inhibited the serum levels of inflammatory cytokines and improved the survival rate in systemic inflammatory response syndrome (SIRS) model mice. Our experiments using a cell line suggested that KPE inhibits the production of inflammatory cytokines by macrophages in hyperinflammatory state. In addition, experiments in vivo showed that the oral administration of KPE inhibited the serum levels of inflammatory cytokines and improved the survival rate in SIRS model mice. Our findings indicated that KPE contributes to alleviating of a hyperinflammatory response.


Anti-inflammatory effect Kawachi-bankan Macrophages RAW264.7 cells SIRS 



Activator protein-1


Bovine serum albumin


Dulbecco’s modified Eagle’s medium


Enzyme-linked immunosorbent assay


Extracellular signal-regulated protein kinase


Fetal bovine serum




c-Jun N-terminal kinase


Kawachi-bankan peel aqueous extract




Mitogen-activated protein kinase


Sodium phosphate buffer


Nuclear factor-κB


Phosphate-buffered saline


Pattern recognition receptors

RPMI 1640

Roswell Park Memorial Institute 1640


Systemic inflammatory response syndrome


Toll-like receptor


Tumor necrosis factor-α



We thank the members of the Advanced Research Support Center (ADRES), Ehime University for allowing use of the animal facility.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Momoko Ishida
    • 1
  • Chihiro Takekuni
    • 1
  • Kosuke Nishi
    • 1
    • 2
  • Takuya Sugahara
    • 1
    • 2
    Email author
  1. 1.Graduate School of AgricultureEhime UniversityMatsuyamaJapan
  2. 2.Food and Health Sciences Research CenterEhime UniversityMatsuyamaJapan

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