Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.227
Hyaluronic Acid Increases Anti-Inflammatory Efficacy of Rectal 5-Amino Salicylic Acid Administration in a Murine Colitis Model
Henusha D. Jhundoo1, Tobias Siefen1, Alfred Liang2, Christoph Schmidt3, John Lokhnauth4, Brice Moulari5, Arnaud Béduneau5, Yann Pellequer5, Crilles Casper Larsen6 and Alf Lamprecht1,5,*
1Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn 53121, Germany
2Tris Pharma, Monmouth Junction, NJ 08852, USA
3Bayer Consumer Care AG, Basel 4052, Switzerland
4Vytaderm, Fair Lawn, NJ 07410, USA
5PEPITE (EA4267) University of Burgundy / Franche-Comté, Besançon 25000, France
6Ferring Pharmaceuticals Inc, Parsippany, NJ 07054, USA
*E-mail: alf.lamprecht@uni-bonn.de
Tel: +49-228-735243, Fax: +82-49-228-735268
Received: December 15, 2020; Revised: April 19, 2021; Accepted: April 27, 2021; Published online: June 1, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone (MPO, moderate, 5-ASA: 1,776 ± 315, 5-ASA+HA: 1,157 ± 561; severe, 5-ASA: 5,742 ± 611, 5-ASA+HA: 2,953 ± 2,611 U/g tissue). Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.
Keywords: Hyaluronic acid, Inflammatory bowel disease, Colitis, Inflammation, 5-amino salicylic acid


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