Yadav, V;
Mai, Y;
McCoubrey, LE;
Wada, Y;
Tomioka, M;
Kawata, S;
Charde, S;
(2021)
5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease.
Biomedicines
, 9
(5)
, Article 578. 10.3390/biomedicines9050578.
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Abstract
5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery.
| Type: | Article |
|---|---|
| Title: | 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/biomedicines9050578 |
| Publisher version: | https://doi.org/10.3390/biomedicines9050578 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | Ulcerative colitis; Crohn’s disease; inflammation; 5 amino levulinic acid; colonic drug delivery; anti-inflammatory; large intestine; drug stability; microbiota metabolism; microbiome |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10129444 |
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