Hyaluronic Acid Increases Anti-Inflammatory Efficacy of Rectal 5-Amino Salicylic Acid Administration in a Murine Colitis Model

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. 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.

Hyaluronic Acid-Conjugated Thermoresponsive Polymer-Based Bioformulation Enhanced Wound Healing and Gut Barrier Repair of a TNBS-Induced Colitis Injury Ex Vivo Model in a Dynamic Perfusion Device

“…Previous studies suggest that structural conformation of HA allows it to form hydrogen bonds or electrostatic interactions with mucin proteins, thus imparting mucoadhesive properties (Figure A). On the other hand, P­(NIPAM) is known to serve as a coating material at physiological temperatures.…”

Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients

“…Although recent studies have demonstrated the possible protective and anti-inflammatory role of HA during colitis [ 19 ], in our experimental conditions, this was not evident, and HA alone did not show any significant amelioration for the severity of colitis in vivo and in ex vivo experiments. Moreover, it has recently been demonstrated that intrarectal HA’s co-administration with Acetylsalicilic acid (ASA) is a very interesting approach to improving the course of colitis [ 20 ]. However, it is important to note that the studies mentioned have employed significantly higher dosages and more frequent administration compared to our experimental plan.…”

Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease

“…This medicine contributes to the removal of reactive oxygen species generated by inflammation and suppresses the production of leukotrienes, which are involved in inflammation 11,12 . Its combination with natural ingredients has also been studied, and the effect is enhanced when combined with hyaluronic acid and extracts of Glycyrrhiza inflata 13–15 . However, it was reported that 5‐ASA may be inactivated by acetylation through acetyltransferases possessed by certain intestinal bacteria 16 .…”

“… 11 , 12 Its combination with natural ingredients has also been studied, and the effect is enhanced when combined with hyaluronic acid and extracts of Glycyrrhiza inflata . 13 , 14 , 15 However, it was reported that 5‐ASA may be inactivated by acetylation through acetyltransferases possessed by certain intestinal bacteria. 16 Therefore, regulation of the intestinal microbiota is important to maximize the effects of 5‐ASA.…”