Pomegranates Provide Potent Lead Compounds for the Treatment of IBD


     Inflammatory bowel disease (IBD)
consists of Crohn’s Disease and Ulcerative Colitis. Both are the result of
dysregulation of the immune system leading to intestinal inflammation and microbial
dysbiosis.

     Ellagic
acid, present in pomegranates interacts with the INIA strain of Bifidobacterium
pseudocatenulatem in the gut to release a metabolite UroA. A synthetic analog,
UAS03 has the same or more potent therapeutic effects in the treatment of IBD.

     Recent
research
published in Nature
Communications
has elucidated the mechanisms of action for both compounds.
UroA and UAS03 enhance the barrier function by inducing up regulation of tight
junction proteins. This is done by activation of aryl hydrocarbon receptor (AhR)
nuclear factor erythroid 2-related factor (Nrf2) dependent pathways.

    
Additionally UroA and UAS03 demonstrate potent anti inflammatory
properties. In vitro both compounds significantly decreased LPS induced IL-6
and TNF-
a in mouse bone marrow
derived macrophages. In vivo the two compounds inhibited LPS induced
peritonitis mouse model. It is amazing that two compounds as simple as these
can be so efficacious in the up regulation of tight junction proteins and in
the inhibition of inflammation.

Old NID
236287

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