Effects of polyphenolic maqui (Aristotelia chilensis) extract on the inhibition of NLRP3 inflammasome and activation of mast cells in a mouse model of Crohn's disease-like colitis

Front Immunol. 2024 Jan 12:14:1229767. doi: 10.3389/fimmu.2023.1229767. eCollection 2023.

Abstract

Introduction: Crohn's disease (CD) involves activation of mast cells (MC) and NF-кB in parallel with the PPAR-α/NLRP3 inflammasome/IL-1β pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue.

Methods: Maqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-α/NLRP3 expression and IL-1β levels.

Results: Compared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while co-treatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1β levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-α signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed.

Conclusion: These outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBS- induced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).

Keywords: Crohn’s disease; NLRP3 inflammasome; anthocyanins; interleukin 1β; maqui; mast cells; polyphenols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthocyanins* / therapeutic use
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Crohn Disease* / chemically induced
  • Crohn Disease* / drug therapy
  • Inflammasomes / metabolism
  • Mast Cells / metabolism
  • Mice
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Peroxisome Proliferator-Activated Receptors

Substances

  • Anthocyanins
  • Inflammasomes
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Peroxisome Proliferator-Activated Receptors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was financially supported by Spanish Ministry of Universities: ‘Margarita Salas’ grants for the training of young doctors. Funded by the Spanish Recovery, Transformation and Resilience Plan and Next Generation EU; PAIDI CTS949 by Junta de Andalucía; and ‘VI Plan Propio de Investigación y Transferencia (Universidad de Sevilla)’ supported by ‘Programa Operativo Fondos Europeos de Desarrollo Regional de Andalucía (2014-2020, FEDER)’.