A new co‐micronized compound of ultramicronized‐Palmitoylethanolamide and Polydatin protects against inflammatory bowel disease through SIRT1/Nrf2 and NF‐kB pathway

Background Palmitoylethanolamide(PEA),has well‐known anti‐inflammatory effects. However, PEA does not possess antioxidant ability. A co‐micronized formulation of ultramicronized PEA(um‐PEA) and Polydatin(Pol) PEA/Pol, a biological precursor of resveratrol with antioxidant activity, could have protective effects on oxidative stress produced by inflammatory processes. Method We evaluated the effects of a co‐micronized PEA/Pol 10mg/kg in a model of DNBS‐induced colitis. Ulcerative colitis was induced in mice by intrarectally injection of DNBS(4 mg in 100 µL of 50% ethanol per mouse). Results Macroscopic and histologic colon alterations and marked clinical signs were observed four days after DNBS and an elevated cytokine production. The myeloperoxidase(MPO) activity assessed neutrophil infiltration was associated with ICAM‐1 and P‐selectin adhesion controls in colons. Oxidative stress was detected with increased poly ADP‐ribose polymerase(PARP) and nitrotyrosine positive staining and malondialdehyde(MDA) levels in inflamed colons. Macroscopic and histologic alteration minimized by oral PEA/Pol, as well as the neutrophil infiltration, inflammatory cytokines release, MDA, Nitrotyrosine, PARP and ICAM‐1 and P‐selectin expressions. PEA/Pol mechanism of action could be related to Sirtuin 1/ Nuclear factor erythroid 2‐related factor 2(Sirt‐1/Nrf2) pathway and nuclear factor(NF)‐kB. PEA/Pol administration inhibited NF‐kB and increased Sirt‐1/Nrf2 expressions. Conclusions Our results show that PEA/Pol is capable of decreasing inflammatory bowel disease(IBD) DNBS‐induced in mice.