The effect of an isoquinoline alkaloid on treatment of periodontitis by regulating the neutrophils chemotaxis

J Leukoc Biol. 2021 Sep;110(3):475-484. doi: 10.1002/JLB.3MA0321-736R. Epub 2021 Jun 28.

Abstract

Neutrophil plays a critical role in the progression of periodontitis. In general, its chemotaxis and activation are benefit for the host defense of bacterial infection and inflammation. However, previous studies have reported that the hyperactive and reactive neutrophils appear to be one of the reasons for tissue destruction in periodontitis tissues. In this study, we investigated an isoquinoline alkaloid Litcubanine A (LA), which from the Traditional Chinese medicinal plant, Litsea cubeba. We found LA showed significant activity in inhibiting neutrophils chemotaxis in the zebrafish yolk sac microinjection model in vivo and in mouse neutrophils in vitro. Further investigation proved that LA could inhibit the expression levels of neutrophil respiratory burst-related and inflammation-related genes CYBB and NCF2, as well as inhibit the activation of MAPK signaling pathway. Moreover, using LA, we successfully achieved the effect of reducing periodontitis bone loss by regulating neutrophil chemotaxis and related functions in a mouse ligature-induced periodontitis model.

Keywords: Litsea cubeba; chemotaxis; neutrophil; periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use*
  • Animals
  • Bone Resorption / pathology
  • Chemotaxis* / drug effects
  • Gene Expression Regulation / drug effects
  • Interleukin-8 / metabolism
  • Isoquinolines / pharmacology
  • Isoquinolines / therapeutic use*
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Neutrophils / pathology*
  • Periodontitis / diagnostic imaging
  • Periodontitis / drug therapy*
  • Periodontitis / pathology
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Respiratory Burst / drug effects
  • Yolk Sac / drug effects
  • Yolk Sac / metabolism
  • Zebrafish

Substances

  • Alkaloids
  • Interleukin-8
  • Isoquinolines
  • Receptors, Chemokine