5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease

Yadav, V; Mai, Y; McCoubrey, LE; Wada, Y; Tomioka, M; Kawata, S; Charde, S; Basit, AW

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-alpha, IL-6, and IL-1 beta 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.

Citation

Yadav, V., Mai, Y., McCoubrey, L., Wada, Y., Tomioka, M., Kawata, S., Charde, S., & Basit, A. (2021). 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease. Biomedicines, 9(5), https://doi.org/10.3390/biomedicines9050578

• Journal Article Type: Article
• Acceptance Date: May 15, 2021
• Publication Date: 2021
• Deposit Date: Dec 21, 2021
• Publicly Available Date: Dec 21, 2021
• Electronic ISSN: 2227-9059
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 5
• DOI: https://doi.org/10.3390/biomedicines9050578
• Keywords: ulcerative colitis; Crohn's disease; inflammation; 5 amino levulinic acid; colonic drug delivery; anti-inflammatory; large intestine; drug stability; microbiota metabolism; microbiome; HEME OXYGENASE-1; FLUORESCENCE; RESECTION; EFFICACY; DELIVERY; SODIUM; MICE; RAT; PH
• Public URL: https://rvc-repository.worktribe.com/output/1553477