, Volume 26, Issue 6, pp 1469–1481 | Cite as

Ex vivo immunomodulatory effect of ethanolic extract of propolis during Celiac Disease: involvement of nitric oxide pathway

  • Oussama Medjeber
  • Kahina Touri
  • Hayet Rafa
  • Zineb Djeraba
  • Mourad Belkhelfa
  • Amira Fatima Boutaleb
  • Amina Arroul-Lammali
  • Houda Belguendouz
  • Chafia Touil-BoukoffaEmail author
Original Article


Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.


Celiac Disease Propolis Nitric oxide pathway Inflammation Cytokines Immunomodulation 



The authors would like to thank the beekeeper Mohamed Kacioui, Dr. Belanteur (Central laboratory, Nafissa Hamoud University Hospital, Algiers, Algeria), Dr. Nassima Behairi (USTHB, Algiers, Algeria), Sarra Benkhelifa (USTHB, Algiers, Algeria) and Fayçal Medjeber (Spectrol Lab, Algeria) for their technical assistance.


This work was supported by national thematic research agency in development health science (ATRSS, ex ANDRS), project code N°43-ANDRS-2011.

Compliance with ethical standards

Disclosure statement

The authors report no declarations of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Oussama Medjeber
    • 1
  • Kahina Touri
    • 1
  • Hayet Rafa
    • 1
  • Zineb Djeraba
    • 1
  • Mourad Belkhelfa
    • 1
  • Amira Fatima Boutaleb
    • 2
  • Amina Arroul-Lammali
    • 1
  • Houda Belguendouz
    • 1
  • Chafia Touil-Boukoffa
    • 1
    Email author
  1. 1.Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological SciencesUniversity of Sciences and Technology Houari Boumediene (USTHB)AlgiersAlgeria
  2. 2.Department of GastroenterologyLamine Debaghine HospitalAlgiersAlgeria

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