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

• Published in: Biomedicines 2021-05, Vol.9 (5), p.578
• Main Authors: Yadav, Vipul, Mai, Yang, McCoubrey, Laura E., Wada, Yasufumi, Tomioka, Motoyasu, Kawata, Satofumi, Charde, Shrikant, Basit, Abdul W.
• Format: Article
• Language: English
• Subjects: 5 amino levulinic acid; Amino acids; Aminolevulinic acid; anti-inflammatory; Citric acid; Colitis; Colon; colonic drug delivery; Crohn’s disease; Dosage; Heme; Heme oxygenase (decyclizing); Humidity; IL-1β; Immunoregulation; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 6; Intestine; Medical research; Microbiota; Oxygenase; Permeability; Pharmacokinetics; Porphyrins; Severe acute respiratory syndrome coronavirus 2; Tumor necrosis factor-α; ulcerative colitis; Work stations
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9050578

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.