An orally administered butyrate-releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium-induced murine colitis.
Butyrate has shown benefits in inflammatory bowel diseases. However, it is not often administered orally because of its rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS).



Male 10 week-old BALB/c mice received DSS (2.5%) in drinking water (for 5 days) followed by DSS-free water for 7 days (DSS group). Oral FBA administration (42.5 mg·kg-1) was started 7 days before DSS as preventive (P-FBA), or 2 days after DSS as therapeutic (T-FBA); both treatments lasted 19 days. One DSS-untreated group received only tap water (CON).



FBA treatments reduced colitis symptoms and colon damage. P-FBA and T-FBA significantly decreased polymorphonuclear cell infiltration score compared with the DSS group. FBA reversed the imbalance between pro- and anti-inflammatory cytokines (reducing inducible NOS protein expression, CCL2 and IL-6 transcripts in colon and increasing TGFβ and IL-10). Morever, P-FBA and T-FBA limited neutrophil recruitment (by expression and localization of the neutrophil granule protease Ly-6G), restored deficiency of the butyrate transporter and improved intestinal epithelial integrity, preventing tight-junction impairment (zonulin-1 and occludin). FBA, similar to its parental compound sodium butyrate, inhibited histone deacetylase-9 and restored H3 histone acetylation, exerting an anti-inflammatory effect through NF-κB inhibition and the up-regulation of PPARγ.



FBA reduces inflammatory intestinal damage in mice indicating its potential as a postbiotic derivative without the problems associated with the oral administration of sodium butyrate.



This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
Department of Pharmacy, University of Naples Federico II, Naples, Italy.|Centre for Biochemical Pharmacology, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK.
Raffaele
R
Simeoli
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Giuseppina
G
Mattace Raso
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Claudio
C
Pirozzi
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Adriano
A
Lama
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Anna
A
Santoro
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Roberto
R
Russo
Centre for Biochemical Pharmacology, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK.
Trinidad
T
Montero-Melendez
Department of Translational Medicine-Pediatric Section and European Laboratory for the Investigation of Food Induced Diseases, University of Naples Federico II, Naples, Italy.
Roberto
R
Berni Canani
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Antonio
A
Calignano
Centre for Biochemical Pharmacology, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, UK.
Mauro
M
Perretti
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Rosaria
R
Meli
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D020556:Neutrophil Infiltration / Q000187:drug effects; D047495:PPAR gamma / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D002087:Butyrates; C000621902:N-(1-carbamoyl-2-phenyl-ethyl)butyramide; D016328:NF-kappa B; D047495:PPAR gamma; D016264:Dextran Sulfate
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